metoprolol profile

Metoprolol is a beta blocker medication primarily used to treat high blood pressure and angina. It works by blocking the effects of adrenaline (epinephrine) on the heart and blood vessels, leading to decreased heart rate and blood pressure. Metoprolol is synthesized via a multi-step process involving a series of chemical reactions, typically starting with a precursor compound and proceeding through various intermediates to achieve the desired final product. Metoprolol is commonly prescribed for its effectiveness in managing cardiovascular conditions, particularly hypertension and angina. It is also sometimes used to prevent migraines and to reduce the risk of heart attack following a heart attack or stroke. The study of metoprolol continues due to its widespread use and the ongoing need to understand its mechanisms of action, potential side effects, and optimal therapeutic applications. Research focuses on areas such as drug interactions, patient compliance, and the development of new formulations and delivery methods.'

Metoprolol: A selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

metoprolol : A propanolamine that is 1-(propan-2-ylamino)propan-2-ol substituted by a 4-(2-methoxyethyl)phenoxy group at position 1. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

ID Source	ID
PubMed CID	4171
CHEMBL ID	13
CHEBI ID	6904
SCHEMBL ID	4093
MeSH ID	M0013686
PubMed CID	11957594
MeSH ID	M0013686

Synonym
AC-19022
metrol
(+/-)-1-(isopropylamino)-3-(p-(beta-methoxyethyl)phenoxy)-2-propanol
metohexal
meijoprolol
unii-geb06nhm23
loresor
metoprololum
einecs 257-166-4
1-(isopropylamino)-3-(4-(2-methoxyethyl)phenoxy)propan-2-ol
1-(4-(2-methoxyethyl)-phenoxy)-3-((1-methylethyl)amino)-2-propanol
geb06nhm23 ,
neobloc
selo-zok
STL301858
AB00053499-21
BRD-A03623303-045-02-0
gtpl553
gp-2175e
2-propanol, 1-[4-(2-methoxyethyl)phenoxy]-3-[(1-methylethyl)amino]-, (.+/-.)-
1-[4-(2-methoxyethyl)phenoxy]-3-(propan-2-ylamino)propan-2-ol
CHEBI:6904 ,
1-(isopropylamino)-3-[4-(2-methoxyethyl)phenoxy]propan-2-ol
(rs)-metoprolol
1-[(1-methylethyl)amino]-3-({4-[2-(methyloxy)ethyl]phenyl}oxy)propan-2-ol
lopressidone
cgp 2175
2-propanol, 1-(4-(2-methoxyethyl)phenoxy)-3-((1-methylethyl)amino)-
hsdb 6531
betalok
beatrolol
presolol
spesicor
cgp-2175
2-propanol, 1-(4-(2-methoxyethyl)phenoxy)-3-((1-methylethyl)amino)-, (+-)-
spesikor
metoprololum [inn-latin]
ccris 4198
preblok
metoprolol [usan:inn:ban]
{2-hydroxy-3-[4-(2-methoxyethyl)phenoxy]propyl}(propan-2-yl)amine
chembl13 ,
(2r,3r)-2,3-dihydroxysuccinic acid;1-(isopropylamino)-3-[4-(2-methoxyethyl)phenoxy]propan-2-ol
bdbm25756
AB00053499
metoprolol
C07202
51384-51-1
dl-metoprolol
DB00264
metoprolol (usan/inn)
D02358
NCGC00021148-03
NCGC00021148-04
cgp2175
toprol
37350-58-6
HMS2090B15
h-93/26
L000669
metoprolol slow release
seroken
rac metoprolol-d7
A2878
NCGC00021148-05
A823609
lopresoretic
CCG-204813
AKOS005927923
1-[4-(2-methoxyethyl)phenoxy]-3-propan-2-ylamino-propan-2-ol
FT-0672383
FT-0672382
FT-0602794
S5430
metoprolol [vandf]
metoprolol [usan]
metoprolol [mi]
1-(4-(2-methoxyethyl)phenoxy)-3-((1-methylethyl)amino)-2-propanol
(+/-)-metoprolol
54163-88-1
metoprolol, (+/-)-
metoprolol [mart.]
metoprolol [hsdb]
metoprolol [inn]
metoprolol [who-dd]
HY-17503
CS-3159
SCHEMBL4093
1-[4-(2-methoxyethyl)phenoxy]-3-[(propan-2-yl)amino]propan-2-ol
BG-0006
lopresol (salt/mix)
2-propanol, 1-[4-(2-methoxyethyl)phenoxy]-3-[(1-methylethyl)amino]-
1-(isopropylamino)-3-[p-(2-methoxyethyl)phenoxy]-2-propanol
lopresoretic (salt/mix)
h 93/26 (salt/mix)
(.+/-.)-metoprolol
NCGC00356981-01
cas-51384-51-1
tox21_303972
dtxcid503309
dtxsid2023309 ,
Q-201400
AB00053499_22
AB00053499_23
1-isopropylamino-3-[4-(2-methoxy-ethyl)-phenoxy]-propan-2-ol
mfcd00599534
SR-01000003148-2
SBI-0050706.P004
FT-0672385
Q409468
3-bromo-4,5-dihydroxybenzylalcohol
BCP09038
BRD-A03623303-045-05-3
SDCCGSBI-0050706.P005
NCGC00021148-21
51384-51-1 (free base)
HMS3886O04
A871296
BCA38451
1-(4-(2-methoxyethyl)phenoxy)-3-(propan-2-ylamino)propan-2-ol
EN300-317058
Z398538014
metoprololum (inn-latin)
metoprololo
metoprolol (mart.)
c07ab02
56392-17-7
metoprolol tartrate
(?)-metoprolol (+)-tartrate
NCGC00094074-01
NCGC00094074-02
rac metoprolol hemi (+)-tartrate
(+/-)-metoprolol (+)-tartrate
AKOS025310917
metoprolol (tartrate)
NCGC00261413-01
(y)-metoprolol (+)-tartrate
tox21_500728
2,3-dihydroxybutanedioic acid;1-[4-(2-methoxyethyl)phenoxy]-3-(propan-2-ylamino)propan-2-ol
(2r,3s)-2,3-dihydroxybutanedioic acid;1-[4-(2-methoxyethyl)phenoxy]-3-(propan-2-ylamino)propan-2-ol
(2r,3s)-2,3-dihydroxybutanedioic acid; bis(1-[4-(2-methoxyethyl)phenoxy]-3-[(propan-2-yl)amino]propan-2-ol)
EN300-7417804

Excerpt	Reference	Relevance
"Metoprolol succinate is a long-acting beta-blocker prescribed for the management of hypertension (HTN) and other cardiovascular diseases. "	( Metabolomic profiling of metoprolol hypertension treatment reveals altered gut microbiota-derived urinary metabolites. Brocker, CN; Flaten, HK; Gonzalez, FJ; Krausz, KW; McDaniel, K; McWilliams, G; Monte, AA; Saben, J; Shelton, SK; Velenosi, T, 2020)	2.3
"Metoprolol (MTP) is a cardio-selective β1-blocker used in hypertension, angina pectoris and chronic heart failure therapies. "	( The Influence of Fatty Acids on Metoprolol - Human Serum Albumin Interaction in Low Affinity Binding Sites: A Multifactorial NMR Approach. Maciazek-Jurczyk, M; Mogielnicki, M; Pentak, D; Ploch, A; Szkudlarek, A, 2018)	2.21
"Metoprolol is a cardioprotective anti-hypertensive agent."	( Modulation of cardiac stem cell characteristics by metoprolol in hypertensive heart disease. Nair, RR; Potnuri, AG; Saheera, S, 2018)	1.45
"Metoprolol still appears to be a suitable pharmacological option in different cardiovascular conditions. "	( Metoprolol in the treatment of cardiovascular disease: a critical reappraisal. Grassi, G, 2018)	3.37
"Metoprolol is an important therapeutic option for children with VVS."	( Twenty-four-hour urine NE level as a predictor of the therapeutic response to metoprolol in children with recurrent vasovagal syncope. Cai, Z; Kong, Q; Liu, M; Pan, Y; Wang, M; Yang, X; Zhao, C, 2019)	1.46
"Metoprolol is a cardioselective competitive beta-1 adrenergic receptor antagonist with antihypertensive properties, devoid of intrinsic sympathomimetic activity. "	( The effects of intraperitoneal metoprolol administration on healing of bone defects in rat tibia: a pilot study. Al Alawy, R; AlHabashneh, R; Hammad, H, 2020)	2.29
"Metoprolol is a selective β1-adrenergic receptor antagonist metabolized by hepatic cytochrome P450s (CYPs). "	( Faster non-renal clearance of metoprolol in streptozotocin-induced diabetes mellitus rats. Kang, HE; Lee, BK; Lee, I; Lee, U, 2013)	2.12
"Metoprolol succinate is a very potent drug for the treatment of hypertension but suffers from poor bioavailability due to its erratic absorption in lower GI tract. "	( Bilayer mucoadhesive microparticles for the delivery of metoprolol succinate: Formulation and evaluation. Dhawan, N; Kumar, K; Patwal, PS; Sharma, H; Vaidya, B; Vaidya, S, 2015)	2.11
"Metoprolol is a selective β-1 adrenergic receptor blocker that undergoes extensive metabolism by the polymorphic enzyme cytochrome P450 2D6 (CYP2D6). "	( Impact of CYP2D6 polymorphisms on clinical efficacy and tolerability of metoprolol tartrate. Burkley, BM; Chapman, AB; Cooper-DeHoff, RM; Dwivedi, R; Garcia, S; Gong, Y; Gums, JG; Hamadeh, IS; Johnson, JA; Langaee, TY; Skaar, TC; Turner, ST, 2014)	2.08
"Metoprolol (MTP) is a compound of concern, considered as an emerging contaminant due to its high consumption, pseudopersistence and potential ecotoxicity. "	( Characterization of metoprolol biodegradation and its transformation products generated in activated sludge batch experiments and in full scale WWTPs. Barceló, D; Buttiglieri, G; Casas, N; Llorca, M; Rodriguez-Mozaz, S; Rodriguez-Roda, I; Rubirola, A, 2014)	2.17
"Metoprolol is a moderately lipophilic β-blocker that in overdose causes direct myocardial depression leading to bradycardia, hypotension, and the potential for cardiovascular collapse."	( Successful treatment of a massive metoprolol overdose using intravenous lipid emulsion and hyperinsulinemia/euglycemia therapy. Barton, CA; Beauchamp, G; Hendrickson, R; Johnson, NB; Mah, ND, 2015)	1.42
"Metoprolol is a β-adrenergic receptor antagonist that is ineffective in younger patients, but may benefit older (≥40 years) VVS patients."	( Rationale for the Assessment of Metoprolol in the Prevention of Vasovagal Syncope in Aging Subjects Trial (POST5). Benditt, DG; Faris, PD; Krahn, AD; Manns, B; Morillo, CA; Raj, SR; Semeniuk, L; Sheldon, RS, 2016)	1.44
"Metoprolol is a β-blocker highly prescribed for the treatment of heart diseases. "	( Identification and characterization of photodegradation products of metoprolol in the presence of natural fulvic acid by HPLC-UV-MS Domingues, MRM; Filipe, OMS; Mota, N; Neves, MGPMS; Santos, EBH; Santos, SAO; Silvestre, AJD; Simões, MMQ, 2017)	2.13
"Metoprolol is a widely used cardioselective beta-blocker. "	( S-metoprolol: the 2008 clinical review. Dasbiswas, A; Dasbiswas, D; Shinde, S, 2008)	2.51
"Metoprolol is a selective beta(1)-adrenergic antagonist extensively used since 1975. "	( Metoprolol succinate combination in the treatment of hypertension. Papademetriou, V; Papadopoulos, DP, )	3.02
"Metoprolol is a lipophilic beta(1) selective adrenergic receptor antagonist used in antihypertensive therapy. "	( Effects of polymorphism of the beta(1) adrenoreceptor and CYP2D6 on the therapeutic effects of metoprolol. Huang, Z; Lv, H; Sang, H; Yang, G; Yao, Y; Yuan, H, )	1.79
"Metoprolol succinate is a widely used medication for the management of hypertension, heart failure, and angina. "	( Metoprolol succinate therapy associated with erythema multiforme. Bisognano, JD; Hong, JA, 2009)	3.24
"Metoprolol is a beta-blocker and its racemic mixture is used for the treatment of hypertension. "	( Influence of quinidine, cimetidine, and ketoconazole on the enantioselective pharmacokinetics and metabolism of metoprolol in rats. Boralli, VB; Coelho, EB; Lanchote, VL, 2009)	2.01
"Metoprolol is a commonly used beta-adrenergic antagonist metabolized by CYP2D6."	( Influence of metoprolol dosage release formulation on the pharmacokinetic drug interaction with paroxetine. Bleske, BE; Brook, R; Kerber, K; Nielsen, J; Shea, M; Stout, SM; Welage, LS, 2011)	1.46
"Metoprolol (MET) is a β1-adrenoceptor antagonist, which is widely used in the treatment of cardiovascular diseases, and α-hydroxymetoprolol (α-OHM) is its hydroxylated metabolite. "	( Simultaneous determination of metoprolol and α-hydroxymetoprolol in human plasma using excitation-emission matrix fluorescence coupled with second-order calibration methods. Gu, HW; Li, SS; Liu, YJ; Su, ZY; Wu, HL; Yin, XL; Yu, RQ, 2012)	2.11
"ER metoprolol succinate is a controlled-release tablet designed to produce even and consistent beta(1)-blockade throughout the 24-hour dosing interval, with less fluctuation in metoprolol plasma concentrations compared with immediate-release metoprolol. "	( Extended-release metoprolol succinate in chronic heart failure. Patterson, JH; Tangeman, HJ, 2003)	1.28
"Metoprolol is a selective beta(1)-adrenergic antagonist extensively used in major fields of cardiology since 1975. "	( [Metoprolol CR/XL: advanced formulation of a classical beta-blocker]. Gudkov, KM; Kobalava, ZhD, 2003)	2.67
"metoprolol. Thus, there is a reduction in coronary collateral flow with metoprolol, probably due to an increase in coronary collateral resistance or a reduction in oxygen demand."	( Coronary collateral perfusion in patients with coronary artery disease: effect of metoprolol. Billinger, M; Hess, OM; Meier, B; Raeber, L; Seiler, C; Windecker, S, 2004)	1.27
"Metoprolol is a widely used beta1-selective beta-blocker in hypertension and tachycardia. "	( Relation between pharmacodynamic and anthropometric parameters during ergometry at rest and after repeated intake of metoprolol in healthy volunteers: results of a pilot study. Koch, HJ; Raschka, C, 2004)	1.98
"Metoprolol tartrate is a short-acting form of metoprolol while metoprolol succinate is a longer acting salt and the commercially available product is designed as a once daily formulation."	( Pharmacokinetics and pharmacodynamics of beta blockers in heart failure. Talbert, RL, 2004)	1.04
"Metoprolol is a first-line drug in the management of patients with acute coronary syndrome; however, when metoprolol was marketed in 1982, women were largely excluded from clinical trials."	( Modulation of metoprolol pharmacokinetics and hemodynamics by diphenhydramine coadministration during exercise testing in healthy premenopausal women. Arsenault, M; Bélanger, PM; Dumesnil, JG; Hamelin, BA; Meibohm, B; Pibarot, P; Pilote, S; Sharma, A, 2005)	1.41
"Metoprolol appears to be an excellent alternative antitremor drug to propranolol in such patients."	( Metoprolol in essential tremor. Jacobs, L; Newman, RP, 1980)	2.43
"Metoprolol is a widely used anti-ischemic drug with a relatively short half-life. "	( Comparison between metoprolol orally osmotic once daily and metoprolol two or three times daily in suppressing exercise-induced and daily myocardial ischemia. Barzilai, Y; Brunel, P; David, D; Gavish, A; Keren, A; Medina, A; Shatboon, D; Tzivoni, D, 1996)	2.07
"Metoprolol is a cardioselective beta blocker that has been shown to improve left ventricular function and symptoms of congestive heart failure (CHF) and also to decrease the number of hospitalizations due to CHF. "	( Rationale, design, and organization of the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF). The International Steering Committee. , 1997)	2
"Metoprolol is a liposoluble beta1-selective adrenoceptor antagonists."	( [Experimental study of metoprolol-induced side effects]. Gergely, J, 1998)	1.33
"Metoprolol is a beta 1-selective adrenoceptor antagonist that is widely used in several indications. "	( Metoprolol: a pharmacoeconomic and quality-of-life evaluation of its use in hypertension, post-myocardial infarction and dilated cardiomyopathy. Benfield, P; Peters, DH, 1994)	3.17
"Metoprolol is a beta1-selective adrenoceptor antagonist."	( A comparison of carvedilol and metoprolol antioxidant activities in vitro. Gu, JL; Lysko, PG; Ohlstein, EH; Ruffolo, RR; Webb, CL; Yue, TL, 2000)	1.31
"The metoprolol CR/Zok is a multi-unit formulation containing metoprolol succinate controlled release (CR/Zok) in the form of individual drug delivery units (microcapsules). "	( Achieving optimal beta1-blockade with metoprolol CR/Zok. Wikstrand, J, 2000)	1.14
"Metoprolol is a beta(1)-selective beta-adrenergic antagonist while carvedilol is a non-selective beta-blocker with additional blockades of alpha(1)-adrenoceptors. "	( Differing beta-blocking effects of carvedilol and metoprolol. Fruhwald, FM; Klein, W; Koshucharova, G; Maier, R; Stoschitzky, K; Watzinger, N; Zweiker, R, 2001)	2.01
"Metoprolol is a selective antagonist of beta(1)-adrenergic receptors."	( Rationale and design of the carvedilol or metoprolol European trial in patients with chronic heart failure: COMET. Cleland, JG; Di Lenarda, A; Hanrath, P; J Remme, W; Komajda, M; Metra, M; Poole-Wilson, PA; Swedberg, K; Torp-Pedersen, C, 2002)	1.3
"Metoprolol was shown to be an effective anti-anginal compound with good tolerance and safety, with gradual improvement in underlying myocardial ischaemia during long term treatment."	( An eighteen months' study of the clinical response to metoprolol, a selective beta1-receptor blocking agent, in patients with angina pectoris. Besterman, EM; Comerford, MB, 1976)	1.23
"With metoprolol there is a lesser increase in diastolic blood pressure and a slight tachycardia."	( Observations in man of hypoglycaemia during selective and non-selective beta-blockade. Corrall, RJ; Davidson, NM; French, EB; Shaw, TR, 1977)	0.71
"Metoprolol is a beta1-selective adrenoceptor blocking drug. "	( Metoprolol: a review of its pharmacological properties and therapeutic efficacy in hypertension and angina pectoris. Avery, GS; Brogden, RN; Heel, RC; Speight, TM, 1977)	3.14
"Metoprolol appears to be an effective and safe drug in the treatment of supraventricular tachycardia."	( Metoprolol in the treatment of supraventricular tachyarrhythmias. Möller, B; Ringqvist, C, 1979)	2.42
"Metoprolol is an effective cardioselective beta adrenergic blocking agent that, under these conditions, reduces catecholamine-induced increases in heart rate and left ventricular dP/dt without significant alteration in ejection fraction, preload or afterload."	( Hemodynamic effects of intravenous metoprolol. Bourdillon, PD; Canepa-Anson, R; Rickards, AF, 1979)	1.26
"6. Metoprolol is a potent short-acting beta-adrenoceptor antagonist; its advantages as a cardioselective agent over practolol in therapeutic use are discussed."	( The effects of propranolol, practolol and metoprolol on exercise-induced tachycardia in relation to plasma levels in man. Ambler, PK; Dorrington, R; Singh, BN; Williams, FM, )	0.91
"Metoprolol is considered to be a class II antiarrhythmic agent that is highly specific for cardiac beta-1 adrenergic receptors, yet long-term administration can produce prolongation of the rate-corrected Q-T interval in humans. "	( Characterization of the electrophysiological effects of metoprolol on isolated feline ventricular myocytes. Barrington, PL; Ten Eick, RE, 1990)	1.97
"Metoprolol is a relatively beta 1-selective beta-blocker used extensively to treat hypertension and angina and as a prophylaxis after myocardial infarction. "	( Controlled release metoprolol. Clinical pharmacokinetic and therapeutic implications. Kendall, MJ; Maxwell, SR; Sandberg, A; Westergren, G, 1991)	2.05
"Metoprolol is a lipophilic, cardioselective beta-adrenergic blocking agent commercially available as a racemic compound. "	( Analysis of metoprolol enantiomers in human serum by liquid chromatography on a cellulose-based chiral stationary phase. Johnson, KA; Marshall, PS; Remmel, RP; Straka, RJ, 1990)	2.1
"Metoprolol may prove to be an effective alternative in managing such side effects as tremors."	( Metoprolol in the treatment of neuroleptic-induced tremor: case report. Chaturvedi, SK, 1987)	2.44
"Metoprolol is a beta 1-adrenoreceptor antagonist which was previously shown to block the teratogenic effects of epinephrine and other catecholamines with beta 1-adrenoreceptor agonist properties."	( Ventricular blood pressure and cardiac output changes in epinephrine- and metoprolol-treated chick embryos. Kolesari, GL; Kuhlmann, RS; Rajala, GM; Schnitzler, HJ, 1988)	1.23
"Metoprolol is an effective antihypertensive agent resulting in a heart rate decrease."	( Beta-adrenoceptor stimulating and blocking agents in essential hypertension: single and combined therapy with terbutaline and metoprolol. Gotzen, R; Meyer-Sabellek, W; Röcker, L; Schulte, KL; Thiede, HM, 1987)	1.2

Excerpt	Reference	Relevance
"Metoprolol has an intermediate hepatic extraction ratio in rats (0.586-0.617), and it is assumed that the liver is exclusively responsible for metoprolol metabolism."	( Faster non-renal clearance of metoprolol in streptozotocin-induced diabetes mellitus rats. Kang, HE; Lee, BK; Lee, I; Lee, U, 2013)	1.4
"Metoprolol has an intermediate hepatic extraction ratio in rats (0.586-0.617), and it is assumed that the liver is exclusively responsible for metoprolol metabolism."	( Faster non-renal clearance of metoprolol in streptozotocin-induced diabetes mellitus rats. Kang, HE; Lee, BK; Lee, I; Lee, U, 2013)	1.4
"Metoprolol has faster onset than amlodipine and less blood pressure variability than metoprolol."	( Effects of different antihypertensive drugs on blood pressure variability in patients with ischemic stroke. Hu, WL; Ji, M; Li, SJ, 2014)	1.85
"Metoprolol has been reported to upregulate cardiac expression of β3-adrenergic receptors (β3AR) in animal models."	( Chronic β1-adrenergic blockade enhances myocardial β3-adrenergic coupling with nitric oxide-cGMP signaling in a canine model of chronic volume overload: new insight into mechanisms of cardiac benefit with selective β1-blocker therapy. Balligand, JL; Baskharoun, MM; Cannavo, A; Dell'Italia, LJ; Dillon, AR; Houser, SR; Jarrett, H; Koch, WJ; Liu, Y; McCormick, RC; Nanayakkara, G; Recchia, FA; Tillson, DM; Trappanese, DM; Tsai, EJ; Woitek, FJ, 2015)	1.14
"Metoprolol has less beta1 receptor affinity compared with atenolol and bisoprolol, and beta1 receptor polymorphisms affect the clinical effects of metoprolol."	( [Which is the preferred perioperative beta-blocker?]. van Klei, WA, 2015)	1.14
"S-metoprolol has been shown to be effective and well-tolerated in patients with coexisting diabetes, COPD, and hyperlipidaemia."	( S-metoprolol: the 2008 clinical review. Dasbiswas, A; Dasbiswas, D; Shinde, S, 2008)	1.63
"Metoprolol has proven its efficacy in reducing cardiovascular events and mortality in patients with hypertension and coronary heart disease."	( Metoprolol succinate combination in the treatment of hypertension. Papademetriou, V; Papadopoulos, DP, )	2.3
"Metoprolol has another metabolic pathway, via CYP2C19, and this may have led to its lack of accumulation."	( Myoclonus after dextromethorphan administration in peritoneal dialysis. Fujita, Y; Ito, Y; Maeda, K; Nagamatsu, T; Nagura, F; Nomura, A; Shimizu, H; Tanaka, A; Tomino, T; Watanabe, T; Yamaguchi, M, 2011)	1.09
"Metoprolol has salts such as tartrate which is used for production of immediate release (IR) and sustained release (SR) forms and succinate used for production of controlled release form (CR/XL)."	( [Evolution of oral drug forms of metoprolol: advantages of long acting modified release forms with modified release]. Belousov, IuB; Leonova, MV; Maneshina, OA, 2010)	1.36
"Metoprolol has equivalent beneficial effects as carvedilol on hemodynamics, LV dilatation and function, but not LV hypertrophy."	( [Comparative effects of carvedilol and metoprolol in preventing from left ventricular remodeling after acute myocardial infarction in rats]. Chen, JL; Chen, ZJ; Gao, RL; Lu, SQ; Ruan, YM; Sun, RC; Tang, YD; Wang, PH; Yang, YJ; Zhang, P, 2001)	1.3
"Metoprolol has proven its efficacy in reducing cardiovascular events and mortality in patients with hypertension and coronary heart disease in large clinical trials."	( [Metoprolol CR/XL: advanced formulation of a classical beta-blocker]. Gudkov, KM; Kobalava, ZhD, 2003)	1.95
"Metoprolol CR/XL has been very well tolerated, overall as well as in all subgroups analyzed."	( How should subgroup analyses affect clinical practice? Insights from the Metoprolol Succinate Controlled-Release/Extended-Release Randomized Intervention Trial in Heart Failure (MERIT-HF). Deedwania, P; Fagerberg, B; Ghali, J; Goldstein, S; Gottlieb, S; Hjalmarson, A; Kjekshus, J; Waagstein, F; Wedel, H; Wikstrand, J, 2003)	1.27
"Metoprolol has not yet been systematically studied in terms of quality of life and incidence of adverse drug reactions (ADRs). "	( [Rationale and methods of the UNAMET study (dose- and CYP2D6-genotype-dependent adverse drug reactions of metoprolol)--a contribution to quality improvement in pharmacotherapy]. Fux, R; Gleiter, CH; Lorenz, G; Meisner, C; Mörike, K; Schwab, M, 2004)	1.98
"Metoprolol has significantly reduced the relative risk of combined end-points (71%) compared to atenolol (53%)."	( [Metoprolol and atenolol in mild-to-moderate chronic heart failure: comparative study]. Celić, V; Dekleva, M; Dimković, S; Kocijancić, M; Pencić, B, )	1.76
"Metoprolol treatment has been shown to restore the reduced beta-adrenoceptor density in dilated cardiomyopathy."	( Effects of metoprolol on myocardial beta-adrenoceptors and Gi alpha-proteins in patients with congestive heart failure. Becker, H; Eschenhagen, T; Hanrath, P; Jakob, H; Schmitz, W; Scholz, H; Schumacher, C; Sigmund, M; Steinfath, M, 1996)	1.41
"Metoprolol pretreatment has been shown to reduce the cardiovascular malformation rate produced by topical doses of dopamine in the stage 24 chick embryo. "	( Tissue and plasma levels of a teratogenic dose of dopamine in the chick embryo following pretreatment with metoprolol or phosphate buffered saline. Kolesari, GL; Kuhlmann, RS; Shields, HE, 1990)	1.93
"Metoprolol has been on the market for 10 years; the research, however, started nearly 20 years earlier and clinical research some 17 years ago. "	( Ten years of clinical experience with metoprolol. Vedin, A, 1987)	1.99

Excerpt	Reference	Relevance
"With metoprolol there was an increase in right ventricular end-diastolic and end-systolic volumes."	( Beta-blockers, left and right ventricular function, and in-vivo calcium influx in muscular dystrophy cardiomyopathy. Blain, A; Blamire, A; Greally, E; Laval, S; MacGowan, GA; Straub, V, 2013)	0.84
"MI+metoprolol group had a lower ROSC rate than MI group in the medium dose subgroup, and a higher ROSC rate than MI group in the high dose subgroup."	( β-Receptor blocker influences return of spontaneous circulation and chemical examination in rats during cardiopulmonary resuscitation. Chen, EX; Gao, YX; Li, LJ; Li, P; Liu, J; Pen, Z; Ren, YX; Zhao, XJ, 2013)	0.9
"Metoprolol prevented the increase in PGC1alpha occupation of the CPT-1B promoter region observed in the diabetic heart without affecting PPAR-alpha occupation."	( Metoprolol represses PGC1alpha-mediated carnitine palmitoyltransferase-1B expression in the diabetic heart. Allard, MF; Dhillon, P; McNeill, JH; Parsons, H; Sharma, V, 2009)	2.52
"Metoprolol can inhibit the expression of GRK2 in lymphocyte of advanced elderly patients with chronic heart failure."	( [Effect of metoprolol on the expression of GRK2 in lymphocyte of advanced elderly patients with chronic heart failure]. Gao, WQ; Han, CG; Liu, YX; Wang, Q; Yang, TS; Zhao, YX; Zhu, P, 2010)	2.19
"Metoprolol can increase the VFT and decrease the excitation threshold of the ischemic myocardium in diabetic rats."	( [Effects of metoprolol on electrophysiology of ischemic and anoxic myocardium in diabetic rats]. Chen, JM; He, L; Jin, HF; Shen, FR; Sun, GJ; Wang, ZJ; Zeng, WP; Zhong, C, 2011)	1.47
"Metoprolol can inhibit the expression of c-fos and has a positive therapeutic effect on rats after AMI; the involvement effect of metoprolol on myocardial infarction might be correlated with its effect on the inhibition of c-fos."	( The effect of c-fos on acute myocardial infarction and the significance of metoprolol intervention in a rat model. Ge, J; Goldstein, S; He, B; Li, Y; Ruiz, G; Zhang, M; Zhang, S, 2013)	1.34
"Metoprolol failed to activate enzyme eNOS activity and NO production to the same level and did not improve the endothelial vasomotor function."	( [Pharmacological modulation of NO synthesis in patients with arterial hypertension and endothelial dysfunction]. Buval'tsev, VI; Guseva, OI; Metel'skaia, VA; Nebieridze, DV; Spasskaia, MB, 2003)	1.04
"Metoprolol treatment can cause an improvement in transmitral and pulmonary venous flows."	( [Effects of beta-blockers on transmitral, pulmonary venous flows, and spontaneous echo-contrast grades in heart failure]. Aydin, M; Cam, F; Doğan, SM; Dursun, A; Gürsürer, M; Madak, H; Onuk, T, 2005)	1.77
"Metoprolol can inhibit sympathetic remodeling and electrical remodeling at the IBZ after MI. "	( Effects of metoprolol on sympathetic remodeling and electrical remodeling at infarcted border zone after myocardial infarction in rabbits. Huang, C; Jian, X; Jiang, H; Lu, Z; Yang, B; Yu, Y; Zhao, D, 2007)	2.17
"Metoprolol tended to lower chest pain and reduce precordial ST-segment elevation due to angioplasty, but the effects were not statistically significant."	( Absence of beneficial effect of intravenous metoprolol given during angioplasty in patients with single-vessel coronary artery disease. Bonnier, JJ; Ciampricotti, R; de Jong, JW; Huizer, T; Roelandt, JR, 1993)	1.27
"Metoprolol did not cause any significant changes compared with the control group."	( Beta-blocker treatment of dilated cardiomyopathy. Beneficial effect of carteolol in mice. Kawai, C; Matsumori, A; Okada, I; Tominaga, M; Yamada, T, 1991)	1
"Metoprolol did not enhance the effect of bromazepam on the psychomotor tests used in this study."	( Interaction of metoprolol with lorazepam and bromazepam. Cameron, GA; Hawksworth, GM; Scott, AK, 1991)	1.36
"Metoprolol caused an increase in LVEDP from 20.8 +/- 1.8 to 27.5 +/- 2.7 mmHg (2.8 +/- 0.2 to 3.7 +/- 0.4 kPa) (P less than 0.01), while TEA induced a decrease in LVEDP from 24.2 +/- 1.4 to 17.8 +/- 1.6 mmHg (3.2 +/- 0.2 to 2.4 +/- 0.2 kPa) (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)"	( Effects of thoracic epidural anaesthesia on central haemodynamics compared to cardiac beta adrenoceptor blockade in conscious rats with acute myocardial infarction. Blomberg, S; Ricksten, SE, 1990)	1
"Metoprolol reduced the increase in pressure resulting from stimulation of the preganglionic trunk of the SCG at 1.0 Hz but enhanced the pressure increase in the cranial circulation evoked by postganglionic stimulation of the SCG at 5.0 Hz."	( Cephalic carotid pressure as a measure of transmission through cervical ganglion. Tuttle, RS, 1985)	0.99
"Metoprolol reduced the increase in stroke volume, and propranolol abolished it."	( Cardiovascular and sympathoadrenal responses to mental stress: influence of beta-blockade. Freyschuss, U; Hjemdahl, P; Juhlin-Dannfelt, A; Linde, B, 1988)	1
"Metoprolol did not produce any central nervous system related side-effects."	( Double-blind, randomized, cross-over clinical trial of metoprolol and propranolol in mild to moderate essential hypertension. Pandhi, P; Sahai, J; Sharma, BK; Sharma, PL; Wahi, PL, 1987)	1.24
"Metoprolol prevented the increase in heart rate but not vasodilatation."	( Effect of felodipine and metoprolol on muscle and skin arteries in hypertensive patients. Clement, DL; De Pue, NY, 1985)	1.29

Excerpt	Reference	Relevance
"Metoprolol-treated rats showed reduced brain neutrophil infiltration and those which infiltrated displayed a high proportion of anti-inflammatory phenotype (N2, YM1"	( Neutrophil β Benito, JM; Calle, D; Carneado-Ruíz, J; Castejón, R; Clemente-Moragón, A; Cortés-Canteli, M; Cussó, L; Desco, M; Fernández-Ferro, JC; Fuster, V; Gómez, M; Ibáñez, B; Moro, MA; Oliver, E; Pradillo, JM; Rallón, N; Sánchez-González, J, 2023)	1.63
"Metoprolol treatment was given to the single drug group and metoprolol combined with amlodipine besylate treatment was given to the combination group."	( Improvement in hemodynamics of amlodipine besylate combined with metoprolol in patients with hypertension complicated by heart failure. Chen, C; Jiao, D; Shen, J; Zhang, W; Zhang, X; Zhu, G, 2023)	1.87
"Metoprolol treatment reduced overall mortality (10% vs 26%, p = 0.03) and the incidence and number of primary ventricular fibrillations during infarct induction."	( Metoprolol blunts the time-dependent progression of infarct size. Fuster, V; Galán-Arriola, C; García-Ruiz, JM; González-Del-Hoyo, M; Higuero-Verdejo, MI; Ibanez, B; Lobo-Gonzalez, M; López-Martín, GJ; Oliver, E; Pizarro, G; Rossello, X; Sánchez-González, J; Vilchez, JP, 2020)	2.72
"IV metoprolol in acute treatment of atrial fibrillation (AF) with rapid ventricular rate (RVR) in the emergency department (ED)."	( Comparison of sustained rate control in atrial fibrillation with rapid ventricular rate: Metoprolol vs. Diltiazem. Fowler, AL; Hargrove, KL; Hughes, DW; Lusk, KA; Neff, LA; Robinson, EE, 2021)	1.36
"Metoprolol treatment did not significantly decrease the mRNA expression of myocardial SERCA2a in the unloaded heart after 2 weeks."	( Effects of carvedilol and metoprolol on the myocardium during mechanical unloading in a rat heterotopic heart transplantation model. Kil, HR; Kim, G; Lee, SS; Quan, C, 2021)	1.64
"Metoprolol-treated ICH mice had improved cardiac and neurological function."	( Metoprolol attenuates intracerebral hemorrhage-induced cardiac damage by suppression of sympathetic overactivity in mice. An, L; Hu, H; Liu, X; Su, Y; Wu, R; Wu, Y; Wuri, J; Yan, T; Yuan, Q; Zhang, L, 2021)	2.79
"Metoprolol treatment prevented the development of chronic cardiac dysfunction by decelerating extracellular cardiac remodeling and inhibiting sympathetic signaling relevant to chronic autonomic dysfunction."	( Stroke-induced chronic systolic dysfunction driven by sympathetic overactivity. Bieber, M; Frantz, S; Heuschmann, PU; Higuchi, T; Hofmann, U; Kleinschnitz, C; Kraft, P; Ritter, O; Schuh, K; Tanai, E; Werner, RA, 2017)	1.18
"In a metoprolol treatment group, metoprolol succinate was administered daily for 12 weeks."	( Metoprolol Inhibits Profibrotic Remodeling of Epicardial Adipose Tissue in a Canine Model of Chronic Obstructive Sleep Apnea. Dai, H; Gong, Y; Han, Y; Li, T; Li, Y; Sheng, L; Sun, L; Xu, J; Yin, S; Yuan, Y; Zhang, Y, 2019)	2.41
"Metoprolol treatment did not delay the onset of heart failure symptoms, improve mitochondrial function, or regress RV hypertrophy."	( Mitochondrial function remains impaired in the hypertrophied right ventricle of pulmonary hypertensive rats following short duration metoprolol treatment. Hickey, AJ; Jones, TLM; Norman, R; Power, AS; Ward, ML, 2019)	1.44
"Metoprolol treatment and ghrelin treatment in KO mice prevented excessive sympathetic activation, decreased plasma epinephrine and norepinephrine levels, and improved heart function and survival rate after MI."	( Excessive sympathoactivation and deteriorated heart function after myocardial infarction in male ghrelin knockout mice. Kangawa, K; Kishimoto, I; Mao, Y; Miyazato, M; Otani, K; Tokudome, T, 2013)	1.11
"Metoprolol pretreatment reduced post-CME myocardial apoptosis possibly through downregulating death receptor-mediated apoptotic pathway."	( [Effects of pretreatment with metoprolol on cardiomyocyte apoptosis and caspase-8 activation after coronary microembolization in rats]. Li, L; Lu, YG; Su, Q; Wang, JY; Wen, WM; Zhou, Y, 2013)	2.12
"In metoprolol plus prazosin treated rabbits, moderate histopathological changes were observed."	( Effect of adrenergic blockers, carvedilol, prazosin, metoprolol and combination of prazosin and metoprolol on paracetamol-induced hepatotoxicity in rabbits. Ahmed, JH; Al-Haroon, SS; Zubairi, MB, )	0.89
"Metoprolol treatment attenuated vessel positive remodeling and reduced vulnerability index (1.61+/-0.58 vs."	( Effect of metoprolol on vulnerable plaque in rabbits by changing shear stress around plaque and reducing inflammation. Changjiang, L; Guihua, J; Huixia, L; Liang, C; Mei, Z; Runyi, S; Xiaobo, H; Xiaojun, C; Xiaonan, L; Xinsheng, X; Yanen, Z; Yun, Z, 2009)	1.48
"Metoprolol pretreatment reduced hepatic expression of proinflammatory cytokines and lowered plasma interleukin-6 (both p < .05)."	( Cardioprotection, attenuated systemic inflammation, and survival benefit of beta1-adrenoceptor blockade in severe sepsis in rats. Ackland, GL; Dyson, A; Gourine, AV; Poputnikov, D; Rudiger, A; Singer, M; Stidwill, R; Yao, ST, 2010)	1.08
"In metoprolol-treated spontaneously hypertensive rats, thrombospondin-4 gene expression correlated with parameters of left ventricular remodelling, while no correlations between thrombospondins and natriuretic peptides were observed."	( Metoprolol treatment lowers thrombospondin-4 expression in rats with myocardial infarction and left ventricular hypertrophy. Aro, J; Leskinen, H; Luodonpää, M; Mustonen, E; Ruskoaho, H; Rysä, J; Vuolteenaho, O, 2010)	2.32
"Metoprolol treatment for 2 weeks improved LV systolic function."	( Divergent effects of losartan and metoprolol on cardiac remodeling, c-kit+ cells, proliferation and apoptosis in the left ventricle after myocardial infarction. Kerkelä, R; Kubin, AM; Leskinen, H; Pieviläinen, O; Ruskoaho, H; Serpi, R; Soini, Y; Tenhunen, O; Tolonen, AM; Vaskivuo, T, 2009)	1.35
"Metoprolol treatment did not effect MAP but reduced heart rate and stroke volume, CO, rCBF, and brain microvascular Po(2), while concurrently increasing systemic vascular resistance (P < 0.05 for all)."	( Metoprolol impairs resistance artery function in mice. Beattie, WS; Bolz, SS; Connelly, KA; El Beheiry, MH; Golam, K; Hare, GM; Heximer, SP; Hu, T; Lidington, D; Liu, E; Mazer, CD; Tsui, AK; Voigtlaender-Bolz, J; Wilson, DF; Zhang, H, 2011)	2.53
"Metoprolol treatment did not prevent the reduction in cardiac function and adverse remodeling, despite a reduction of the inflammatory stress response."	( Role of heart rate reduction in the prevention of experimental heart failure: comparison between If-channel blockade and β-receptor blockade. Becher, PM; Lindner, D; Miteva, K; Savvatis, K; Schmack, B; Schultheiss, HP; Tschöpe, C; Van Linthout, S; Westermann, D; Zietsch, C, 2012)	1.1
"Metoprolol treatment improved in vagal tone assessed by short-term spectral analysis. "	( Effects on heart rate variability of metoprolol supplementary to ongoing ACE-inhibitor treatment in Type I diabetic patients with abnormal albuminuria. Ebbehøj, E; Hansen, KW; Knudsen, ST; Mogensen, CE; Mølgaard, H; Poulsen, PL, 2002)	2.03
"Metoprolol treatment is associated with a decreased duration of PWM and PWD and this may reflect a reduction in the probability of atrial fibrillation in heart failure patients."	( Long-term effects of beta blocker therapy on P-wave duration and dispersion in congestive heart failure patients: a new effect? Akkus, MN; Camsari, A; Cin, VG; Döven, O; Pekdemir, H; Yenihan, S, 2003)	1.04
"Metoprolol treatment can cause an improvement in transmitral and pulmonary venous flows."	( [Effects of beta-blockers on transmitral, pulmonary venous flows, and spontaneous echo-contrast grades in heart failure]. Aydin, M; Cam, F; Doğan, SM; Dursun, A; Gürsürer, M; Madak, H; Onuk, T, 2005)	1.77
"Metoprolol succinate treatment was begun at 50 mg daily and titrated to a dose that lowered blood pressure to <140/90 mm Hg."	( Metoprolol succinate, a selective beta-adrenergic blocker, has no effect on insulin sensitivity. Falkner, B; Francos, G; Kushner, H, 2006)	2.5
"Metoprolol treatment was initiated in 27 patients (group 1), meanwhile 19 patients could not take metoprolol due to diverse contraindications (group 2)."	( Coronary angioplasty induced oxidative stress and its relation with metoprolol use and plasma homocysteine levels. Ciçek, D; Cin, VG; Kara, AA; Pekdemir, H; Tamer, L; Yildirim, H; Yurtdaş, M, 2006)	1.29
"Metoprolol treatment restored TNI phosphorylation, decreased Ca(2+) sensitivity of tension development and of myosin-ATPase activity, but did not alter the tension-dependent ATP consumption."	( Chronic treatment with carvedilol improves Ca(2+)-dependent ATP consumption in triton X-skinned fiber preparations of human myocardium. Bloch, W; Boelck, B; Brixius, K; Grafweg, S; Hoyer, F; Lu, R; Mehlhorn, U; Pott, C; Schwinger, RH, 2007)	1.06
"Metoprolol tartrate-treated patients with body mass index (BMI) >30 kg/m2 had a statistically significant greater weight gain than comparable carvedilol-treated patients."	( Body weight changes with beta-blocker use: results from GEMINI. Anderson, KM; Bakris, GL; Bangalore, S; Bell, DS; Fonseca, V; Holdbrook, FK; Katholi, RE; Lukas, MA; McGill, JB; Messerli, FH; Phillips, RA; Raskin, P; Wright, JT, 2007)	1.06
"Metoprolol treatment produced a slight but significant reduction in serum glucose levels with elevation in serum insulin levels, while atenolol produced a slight increase in glucose levels but no effect on insulin levels."	( Comparative evaluation of atenolol and metoprolol on cardiovascular complications associated with streptozotocin-induced diabetic rats. Bhadada, SV; Goyal, RK, 2007)	1.33
"Metoprolol treatment of hypertensive patients with hepatic cirrhosis resulted in development of bradycardia."	( [Pharmacokinetics of enalapril and metoprolol in hypertensive patients with hepatic pathology]. Drozdov, VN; Lazebnik, LB; Mikheeva, OM; Petrakov, AV; Sil'vestrova, SIu, 2007)	1.34
"Metoprolol in the treatment of hypertensive patients with hepatic cirrhosis should be used with caution because of disturbance of its metabolism and possible cumulative effects."	( [Pharmacokinetics of enalapril and metoprolol in hypertensive patients with hepatic pathology]. Drozdov, VN; Lazebnik, LB; Mikheeva, OM; Petrakov, AV; Sil'vestrova, SIu, 2007)	1.34
"Metoprolol-treated and untreated rats were subjected to the same treadmill running program for 12 weeks. "	( Effect of beta-adrenergic receptor blockade on development of training-induced bradycardia in rats. Nylander, E, 1981)	1.71
"Metoprolol treatment lowered blood pressure and heart rate in all subjects."	( Sympathetic outflow to muscles during treatment of hypertension with metoprolol. Aberg, H; Strömgren, E; Sundlöf, G; Wallin, BG, )	1.09
"More metoprolol-treated than placebo-treated patients withdrew because of cardiovascular adverse experience mainly during the very early phase."	( Göteborg Metoprolol Trial: tolerance. Herlitz, J; Hjalmarson, A; Pennert, K; Vedin, A; Wedel, H; Wilhelmsen, L; Wilhelmsson, C, 1984)	1.14
"3. Metoprolol treatment at a daily dose of 250 mg kg-1 lowered blood pressure and decreased left ventricular hypertrophy index during the control diet."	( Improvement of cardiovascular effects of metoprolol by replacement of common salt with a potassium- and magnesium-enriched salt alternative. Karppanen, H; Laakso, J; Mervaala, EM; Vapaatalo, H, 1994)	1.07
"Metoprolol-treated patients responded favorably, as expressed by improved exercise cardiac index ([mean +/- SD] placebo 4.8 +/- 1.6 to 4.7 +/- 1.8 liters/min per m2, metoprolol 4.3 +/- 1.1 to 5.4 +/- 1.9 liters/min per m2, p = 0.0001) and stroke work index (placebo 44 +/- 20 to 41 +/- 27 g.m/m2, metoprolol 35 +/- 16 to 58 +/- 28 g.m/m2, p < 0.0001). "	( Improved exercise hemodynamic status in dilated cardiomyopathy after beta-adrenergic blockade treatment. Andersson, B; Hamm, C; Hjalmarson, A; Persson, S; Sinagra, G; Waagstein, F; Wikström, G, 1994)	1.73
"Metoprolol treatment has been shown to restore the reduced beta-adrenoceptor density in dilated cardiomyopathy."	( Effects of metoprolol on myocardial beta-adrenoceptors and Gi alpha-proteins in patients with congestive heart failure. Becker, H; Eschenhagen, T; Hanrath, P; Jakob, H; Schmitz, W; Scholz, H; Schumacher, C; Sigmund, M; Steinfath, M, 1996)	1.41
"Metoprolol treatment restores the blunted inotropic response to milrinone in patients with heart failure, indicating that postreceptor events (e.g., increase in inhibitory G-protein) are favorably influenced."	( Improvement of postreceptor events by metoprolol treatment in patients with chronic heart failure. Böhm, M; Deutsch, HJ; Hartmann, D; Rosée, KL; Stäblein, A, 1997)	1.29
"Metoprolol treatment tended to normalize LV end-diastolic pressure (LVEDP)."	( Comparative efficacy of a DA2/alpha2 agonist and a beta-blocker in reducing adrenergic drive and cardiac fibrosis in an experimental model of left ventricular dysfunction after coronary artery occlusion. Bernasconi, R; Bongrani, S; Calvillo, L; Fiordaliso, F; Jeremic, G; Latini, R; Luvarà, G; Masson, S; Razzetti, R; Rondelli, I; Torri, M, 1998)	1.02
"Metoprolol treatment significantly increased the postprandial responses of very low density lipoprotein (VLDL) and VLDL remnants to a mixed meal-type of oral fat tolerance test."	( Effects of a cardioselective beta-blocker on postprandial triglyceride-rich lipoproteins, low density lipoprotein particle size and glucose-insulin homeostasis in middle-aged men with modestly increased cardiovascular risk. Boquist, S; Danell-Toverud, K; Hamsten, A; Hellénius, ML; Karpe, F; Ruotolo, G, 1998)	1.02
"Metoprolol treatment led to a marked reduction in the recurrence of arrhythmic events."	( Comparison of metoprolol and sotalol in preventing ventricular tachyarrhythmias after the implantation of a cardioverter/defibrillator. Hauer, B; Schwick, NG; Seidl, K; Senges, J; Zahn, R, 1998)	1.38
"Metoprolol treatment of rats with CHF results in an improved ability to excrete both short- and long-term sodium loads."	( Effect of metoprolol administration on renal sodium handling in experimental congestive heart failure. DiBona, GF; Sawin, LL, 1999)	2.15
"Metoprolol treatment tended to increase right ventricular weight and heart weight (p < 0.05)."	( Effect of carvedilol in comparison with metoprolol on myocardial collagen postinfarction. Chow, LT; Sanderson, JE; Wei, S, 2000)	1.3
"Metoprolol treatment (60 mg/kg/day via gastric gavage) was started on the second day after surgery and continued until sacrifice at 6 weeks after myocardial infarction."	( Metoprolol attenuates postischemic depressed myocardial function in papillary muscles isolated from normal and postinfarction rat hearts. Ding, B; Min, JY; Morgan, JP; Sullivan, MF; Wang, JF, 2001)	2.47
"Metoprolol pre-treatment had no effect on the cytochrome-P-450 level in the microsomes nor on the rate of metabolism of four standard substrates."	( Metabolism of metoprolol in the rat in vitro and in vivo. Arfwidsson, A; Borg, KO; Hoffmann, KJ; Skånberg, I, 1976)	1.34
"Metoprolol pretreatment (1 mg/kg i.v.) enhanced the sustained pressor response to cocaine, in part due to increased heart rate and mesenteric vascular resistances."	( Adrenergic mechanisms underlying cardiac and vascular responses to cocaine in conscious rats. Branch, CA; Knuepfer, MM, 1992)	1
"Metoprolol treatment did not influence the resting levels of the fibrinolytic variables studied, but tended to enhance the t-PA response to CWT and further reduce PAI-1 during adrenaline infusion."	( Influence of metoprolol treatment on sympatho-adrenal activation of fibrinolysis. Angelin, B; Hjemdahl, P; Larsson, PT; Olsson, G; Wiman, B, 1990)	1.37
"All metoprolol treatments produced a statistically significant beta 1-blockade (measured as percent reduction of exercise induced tachycardia) throughout the whole day compared to placebo except in the 100 mg study where the effect of once daily CT did not differ from placebo during the last 6 hours."	( Pharmacokinetic and pharmacodynamic comparison of metoprolol CR/ZOK once daily with conventional tablets once daily and in divided doses. Bergstrand, R; Lücker, P; Moore, G; Olofsson, B; Wieselgren, I, 1990)	1.01
"Metoprolol pretreatment has been shown to reduce the cardiovascular malformation rate produced by topical doses of dopamine in the stage 24 chick embryo. "	( Tissue and plasma levels of a teratogenic dose of dopamine in the chick embryo following pretreatment with metoprolol or phosphate buffered saline. Kolesari, GL; Kuhlmann, RS; Shields, HE, 1990)	1.93
"In metoprolol treated patients in whom the arrhythmia frequency was reduced by greater than 75% after three days of treatment, mortality was lower as compared to those metoprolol treated patients who did not show this treatment response (3% vs 28%, P = 0.013)."	( Evaluation of antiarrhythmic effect of metoprolol treatment after acute myocardial infarction: relationship between treatment responses and survival during a 3-year follow-up. Olsson, G; Rehnqvist, N, 1986)	1.05
"Metoprolol-treated SHR showed a trend toward higher capillary numerical densities consistent with their attenuation of hypertrophy."	( Sympathetic nerves modify mitochondrial and capillary growth in normotensive and hypertensive rats. Tomanek, RJ, 1989)	1
"More metoprolol-treated patients withdrew because of depression (6 vs less than 1%; p = 0.03) and impotence (5 vs less than 1%; p = 0.03)."	( Influence of beta 2 agonism and beta 1 and beta 2 antagonism on adverse effects and plasma lipoproteins: results of a multicenter comparison of dilevalol and metoprolol. Ahmad, S; Glasser, SP; Lucas, C; Lutz, LJ; Materson, BJ; Morledge, JH; Ramanathan, KB; Saunders, E; Schnaper, HW; Vlachakis, ND, 1989)	0.93
"Metoprolol treatment caused an 8% decrease in heart rate and a 13% decrease in blood pressure and led to a rise in plasma triglycerides, 24%, 17% and 34% after 1, 3 and 6 months of metoprolol treatment, respectively."	( Effect of metoprolol on plasma lipids and arterial intimal lipid deposition in spontaneously hypertensive rats. Eklund, A; Jönsson, L; Ostlund-Lindqvist, AM; Sjöblom, L, 1989)	1.4
"Metoprolol treatment led to a substantial elevation of the plasma triacylglycerol level and, with time, a reduced cholesterolemic response."	( Effects of diet and metoprolol on lipid levels in the blood plasma and morphology of the heart and intramural branches of coronary arteries of spontaneously hypertensive male rats. A 9-month study. Eklund, A; Jönsson, L; Ostlund-Lindqvist, AM; Sjöblom, L, 1989)	1.32
"In metoprolol-treated dogs, DPH produced no significant changes in RSR (90 +/- 28 to 144 +/- 67 to 100 +/- 51 ng of ANG l/hr-min)."	( Role of adrenoceptors in diphenylhydantoin-stimulated renin release. Cadnapaphornchai, P; Kellner, D; McDonald, FD, 1989)	0.79
"Metoprolol treatment generated better scores than did placebo or atenolol treatment for proofreading, visual-motor performance, and several measures of complex managerial competence."	( Impact of beta-blockade on complex cognitive functioning. DePadova, A; McGlynn, T; Piasecki, M; Pogash, R; Streufert, S, 1988)	1
"The metoprolol-treated animals in groups 1 and 2 had a reduction of atherosclerosis compared with their respective controls."	( Atherosclerosis in rabbits identified as high and low responders to an atherogenic diet and the effect of treatment with a beta 1-blocker. Bondjers, G; Bräutigam, J; Lindqvist, P; Nordborg, C; Olsson, G; Ostlund-Lindqvist, AM, 1988)	0.76
"Metoprolol treatment also attenuates circadian variation of silent ischemia."	( Effects of titrated beta blockade (metoprolol) on silent myocardial ischemia in ambulatory patients with coronary artery disease. Coy, K; Imperi, GA; Lambert, CR; Lopez, L; Pepine, CJ, 1987)	1.27
"Metoprolol treatment reduced both the resting tremor and tremor following mental activity, but the drug-induced change in the response to mental stress was more pronounced than the drug-induced reduction in resting tremor."	( Attenuation of response to mental stress in patients with essential tremor treated with metoprolol. Gengo, FM; Kalonaros, GC; McHugh, WB, 1986)	1.21
"Metoprolol-treated patients had an improvement in mean exercise capacity by 3 mets (p less than .0001) while experiencing a significant improvement in functional classification (p less than .001) during both the double-blind and open-label crossover studies and had an improved ejection fraction during the double-blind study (p less than .02)."	( Improvement in symptoms and exercise tolerance by metoprolol in patients with dilated cardiomyopathy: a double-blind, randomized, placebo-controlled trial. Engelmeier, RS; Gunnar, RM; O'Connell, JB; Rad, N; Scanlon, PJ; Walsh, R, 1985)	1.24
"Treatment with metoprolol postinjury was associated with a decrease in HW/BW ratio and COL1/COL3 expression compared to uncontrolled rats."	( Metoprolol Mitigates Ischemic Heart Remodeling and Fibrosis by Increasing the Expression of AKAP5 in Ischemic Heart. Wang, H; Wang, Q; Wang, Z; Zhang, B; Zhang, X; Zhu, F, 2022)	2.5
"Treatment with metoprolol was associated with more negative LS values of the apical segment (-2.8%; 95% CI, -4.2% to -1.3%; P < .001) and the mid segment (-1.1%; 95% CI, -2.0% to -0.3%; P = .007)."	( Metoprolol Improves Left Ventricular Longitudinal Strain at Rest and during Exercise in Obstructive Hypertrophic Cardiomyopathy. Andersen, MJ; Dybro, AM; Jensen, MK; Nielsen, RR; Pedersen, ALD; Poulsen, SH; Rasmussen, TB, 2023)	2.69
"Treatment with metoprolol improved LV GLS upon exercise, indicating a beneficial effect of β-blocker treatment on LV systolic function."	( Metoprolol Improves Left Ventricular Longitudinal Strain at Rest and during Exercise in Obstructive Hypertrophic Cardiomyopathy. Andersen, MJ; Dybro, AM; Jensen, MK; Nielsen, RR; Pedersen, ALD; Poulsen, SH; Rasmussen, TB, 2023)	2.69
"Mice treated with metoprolol experienced a reduced heart rate with no difference in blood pressure."	( Beta1-receptor blockade attenuates atherosclerosis progression following traumatic brain injury in apolipoprotein E deficient mice. Eitzman, DT; Guo, C; Lawrence, DA; Silaghi, P; Su, EJ; Venugopal, J; Wang, J, 2023)	1.23
"Pretreatment with metoprolol + bromocriptine + tamsulosin rescued the retina in all genetic backgrounds, starting at doses of 0.2 mg/kg metoprolol, 0.02 mg/kg bromocriptine, and 0.01 mg/kg tamsulosin in the Gnat1-/- mice."	( A Mixture of U.S. Food and Drug Administration-Approved Monoaminergic Drugs Protects the Retina From Light Damage in Diverse Models of Night Blindness. Choi, EH; Gardella, A; Kefalov, VJ; Leinonen, H; Palczewski, K, 2019)	0.84
"Treatment with metoprolol effectively attenuated cardiac hypertrophy and reversed pressure overload induced changes on Dyrk1A and ASF, and alternative splicing of CaMKIIδ (all P < 0.05)."	( [Metoprolol attenuates pressure overload-induced myocardial hypertrophy through modulating Dryk1A-ASF-CaMKIIδ signaling pathways]. Gu, QQ; Lu, XC; Sheng, HZ; Yao, J; Zhu, JH, 2013)	1.64
"Treatment with metoprolol prevented MR-associated oxidation of NO biosensor soluble guanylyl cyclase (sGC) within NLR."	( Chronic β1-adrenergic blockade enhances myocardial β3-adrenergic coupling with nitric oxide-cGMP signaling in a canine model of chronic volume overload: new insight into mechanisms of cardiac benefit with selective β1-blocker therapy. Balligand, JL; Baskharoun, MM; Cannavo, A; Dell'Italia, LJ; Dillon, AR; Houser, SR; Jarrett, H; Koch, WJ; Liu, Y; McCormick, RC; Nanayakkara, G; Recchia, FA; Tillson, DM; Trappanese, DM; Tsai, EJ; Woitek, FJ, 2015)	0.76
"Treatment with metoprolol of adults with chronic, moderate to severe AR had no effect on LV volumes."	( Controlled release metoprolol for aortic regurgitation: a randomised clinical trial. Aakhus, S; Broch, K; Fosså, K; Gullestad, L; Hopp, E; Lønnebakken, MT; Massey, R; Stueflotten, W; Urheim, S, 2016)	1.12
"Treatment with metoprolol reduced insignificantly the viral load and body weight loss (experiment A and B) but led to a significant reduction of myocardial histopathology in experiment A."	( Cardioprotective effect of NO-metoprolol in murine coxsackievirus B3-induced myocarditis. Dahlke, K; Decker, M; Glück, B; Krumbholz, A; Lehmann, J; Wutzler, P; Zell, R, 2010)	0.99
"Pretreatment with metoprolol CR/XL prior to DSE blunted the dobutamine-induced increase of FS and Vcfc in homozygous Arg389 carriers to the level of subjects carrying the Gly389 allele."	( The Arg389Gly β1-adrenoceptor gene polymorphism influences the acute effects of β-adrenoceptor blockade on contractility in the human heart. Böhm, M; Hellmich, M; Huntgeburth, M; La Rosée, K; Rosenkranz, S; Schnabel, P; ten Freyhaus, H, 2011)	0.69
"Treatment with metoprolol decreased systolic blood pressure at 21 months only but improved survival, decreased ventricular weight, prevented chamber dilation, reduced inflammation, decreased fibrosis, attenuated action potential prolongation, improved systolic and diastolic function, decreased stiffness and improved endothelium-independent vascular responses."	( Chronic β-adrenoceptor antagonist treatment controls cardiovascular remodeling in heart failure in the aging spontaneously hypertensive rat. Brown, L; Chan, V; Fenning, A; Hoey, A, 2011)	0.71
"The treatment with metoprolol 1 mg/kg/h was initiated in the third week post-infarct for a period of 6 weeks."	( Selective beta1-blockade attenuates post-infarct remodelling without improvement in myocardial energy metabolism and function in rats with heart failure. Bollano, E; Omerovic, E; Soussi, B; Waagstein, F, 2003)	0.64
"Treatment with metoprolol had no effect on PCr/ATP and LV function."	( Selective beta1-blockade attenuates post-infarct remodelling without improvement in myocardial energy metabolism and function in rats with heart failure. Bollano, E; Omerovic, E; Soussi, B; Waagstein, F, 2003)	0.66
"Treatment with metoprolol was associated with a 13.5% absolute reduction of AF (P =.16; OR, 0.58 [0.29 to 1.17]."	( A comparison between oral antiarrhythmic drugs in the prevention of atrial fibrillation after cardiac surgery: the pilot study of prevention of postoperative atrial fibrillation (SPPAF), a randomized, placebo-controlled trial. Auer, J; Berent, R; Eber, B; Hartl, P; Lamm, G; Lassnig, E; Lehner, E; Ng, CK; Puschmann, R; Schwarz, C; Strasser, U; Weber, T, 2004)	0.66
"Treatment with metoprolol alone resulted in a trend to a lower risk for postoperative AF."	( A comparison between oral antiarrhythmic drugs in the prevention of atrial fibrillation after cardiac surgery: the pilot study of prevention of postoperative atrial fibrillation (SPPAF), a randomized, placebo-controlled trial. Auer, J; Berent, R; Eber, B; Hartl, P; Lamm, G; Lassnig, E; Lehner, E; Ng, CK; Puschmann, R; Schwarz, C; Strasser, U; Weber, T, 2004)	0.66
"Treatment with metoprolol (n=10) or propranolol (n=10) produced no changes in the cortisol or prolactin responses to hypoglycaemia."	( Cortisol, growth hormone and prolactin responses to insulin-induced hypoglycaemia in hyperthyroid patients before and during beta-adrenoceptor blockade. Anderberg, B; Kågedal, B; Karlberg, BE; Nilsson, OR, 1980)	0.6
"Treatment with metoprolol or placebo started as soon as possible after the patient's arrival in hospital and was continued for 90 days."	( Effect on mortality of metoprolol in acute myocardial infarction. A double-blind randomised trial. Elmfeldt, D; Herlitz, J; Hjalmarson, A; Holmberg, S; Málek, I; Nyberg, G; Rydén, L; Swedberg, K; Vedin, A; Waagstein, F; Waldenström, A; Waldenström, J; Wedel, H; Wilhelmsen, L; Wilhelmsson, C, 1981)	0.91
"Treatment with metoprolol for two years after coronary artery bypass grafting did not significantly change exercise capacity or electrocardiographic signs of myocardial ischaemia."	( Metoprolol treatment for two years after coronary bypass grafting: effects on exercise capacity and signs of myocardial ischaemia. Caidahl, K; Herlitz, J; Hjalmarson, A; Lurje, L; Sjöland, H, 1995)	2.09
"Pretreatment with metoprolol tartrate at any dose did not significantly reduce terbutaline's potential."	( Cardiovascular teratogenicity of terbutaline and ritodrine in the chick embryo. Kolesari, GL; Kuhlmann, RS; Lawrence, JM; Lenselink, DR, 1994)	0.61
"Treatment with metoprolol caused ANF to rise further to 147% of the basal level at 5 h (P = 0.017) and 112% at 24 h (P = 0.029)."	( Effect of low dose beta blockers on atrial and ventricular (B type) natriuretic factor in heart failure: a double blind, randomised comparison of metoprolol and a third generation vasodilating beta blocker. Chan, SK; Chan, WW; Hung, YT; Raymond, K; Sanderson, JE; Shum, IO; Woo, KS, 1995)	0.83
"Dogs treated with metoprolol had a marked decrease in CPT-I activity (0.46 +/- 0.03 vs."	( Beta-receptor blockade decreases carnitine palmitoyl transferase I activity in dogs with heart failure. Kerner, J; Panchal, AR; Sabbah, HN; Stanley, WC, 1998)	0.62
"Treatment with metoprolol CR/XL was associated with a 34% decrease in all-cause mortality, 38% decrease in cardiovascular mortality, 41% decrease in sudden death, and 49% decrease in death due to progressive heart failure."	( The mortality effect of metoprolol CR/XL in patients with heart failure: results of the MERIT-HF Trial. Goldstein, S; Hjalmarson, A, 1999)	0.95
"Treatment with metoprolol 2 h before the endoscopy has been shown to decrease the incidence of myocardial ischaemia during ERCP."	( Vagal withdrawal during endoscopic retrograde cholangiopancreatography. Christensen, M; Rasmussen, V; Rosenberg, J; Schulze, S, 2000)	0.65
"Treatment with metoprolol CR/XL was initiated at a low dosage of 12.5 to 25 mg once daily and gradually increased at 2-weekly intervals until the target dosage (200 mg once daily) or maximal tolerated dosage had been attained in patients receiving standard therapy for heart failure."	( Metoprolol: a review of its use in chronic heart failure. Markham, A; Prakash, A, 2000)	2.09
"Treatment with metoprolol CR/XL significantly reduced the incidence of sudden death and death due to progressive heart failure."	( Metoprolol: a review of its use in chronic heart failure. Markham, A; Prakash, A, 2000)	2.09
"The treatment with metoprolol was given by subcutaneously implanted minipumps and was initiated at 3 days postinfarct and during the period of 4 weeks."	( Selective beta(1)-blockade improves cardiac bioenergetics and function and decreases neuroendocrine activation in rats during early postinfarct remodeling. Bollano, E; Hjalmarson , A; Kujacic, V; Madhu, B; Mobini, R; Omerovic, E; Soussi, B; Waagstein, F, 2001)	0.63
"Treatment with metoprolol CR/XL compared to placebo resulted in significant reductions in all predefined mortality end points including: total mortality, 45 versus 72 deaths (risk reduction 39%; 95% confidence interval 11% to 58%; p = 0.0086); sudden death, 22 vs."	( Metoprolol controlled release/extended release in patients with severe heart failure: analysis of the experience in the MERIT-HF study. Fagerberg, B; Goldstein, S; Kjekshus, J; Waagstein, F; Wedel, H; Wikstrand, J, 2001)	2.09
"Treatment with metoprolol CR/XL compared with placebo resulted in a significant reduction in total mortality (relative risk [RR], 0.61; 95% confidence interval [CI], 0.44-0.84; P =.0022), mainly because of reductions in sudden death (RR, 0.51; 95% CI, 0.33-0.79; P =.0022) and mortality from worsening heart failure (RR, 0.49; 95% CI, 0.25-0.99; P =.042)."	( Effects of metoprolol CR/XL on mortality and hospitalizations in patients with heart failure and history of hypertension. Denny, M; Fenster, P; Herlitz, J; Heywood, T; Masszi, G; Rasmussen, S; Thorgeirsson, G; Wachtell, K; Wikstrand, J, 2002)	1.04
"Treatment with metoprolol CR/XL in women resulted in a 21% reduction in the primary combined end point of all-cause mortality/all-cause hospitalizations (164 versus 137 patients; P=0.044)."	( Metoprolol CR/XL in female patients with heart failure: analysis of the experience in Metoprolol Extended-Release Randomized Intervention Trial in Heart Failure (MERIT-HF). Deedwania, PC; Ghali, JK; Gottlieb, SS; Piña, IL; Wikstrand, JC, 2002)	2.1
"3. Treatment with metoprolol also lowered the systolic blood pressure of isolated rats but only when a larger dose (10 mg/kg) was given."	( Prevention and reversal of isolation-induced systolic arterial hypertension in rats by treatment with beta-adrenoceptor antagonists. Bennett, T; Gardiner, SM, 1979)	0.58
"Treatment with metoprolol, 50--150 mg three times daily for 4--17 weeks, had no effect on the plasma level of glycerol, free fatty acids, triglycerides or glucose under basal conditions, neither in the supine nor in the upright position."	( Effect of metoprolol on blood glycerol, free fatty acids, triglycerides and glucose in relation to plasma catecholamines in hypertensive patients at rest and following submaximal work. Hansson, BG; Hökfelt, B; Nilsson, A, 1978)	1
"Pretreatment with metoprolol in a dose resulting in "therapeutic" plasma levels significantly reduced platelet accumulation by 48% in unbranched aorta, 65% at intercostal, and 53% at coronary artery bifurcations.(ABSTRACT TRUNCATED AT 250 WORDS)"	( Inhibition of platelet accumulation by beta 1-adrenoceptor blockade in the thoracic aorta of rabbits subjected to experimental sympathetic activation. Björk, H; Pettersson, K, 1992)	0.61
"Pretreatment with metoprolol selectively blocked the response to a moderate dose of prenalterol but did not block the response to terbutaline."	( Beta adrenergic influence on esophageal and colonic motility in man. Lyrenäs, E, 1985)	0.59
"Treatment with metoprolol, which was associated with adequate beta-adrenergic blockade and an antihypertensive effect, resulted in a significant increase (p less than 0.05) in the binding of the beta-adrenergic antagonist (-)-(3H)-dihydroalprenolol and a 50% increase (p less than 0.01) in the maximum lipolytic response to the beta-adrenergic agonist isopropylnoradrenaline."	( Long-term beta 1-selective adrenergic blockade and adrenergic receptors in human subcutaneous adipocytes. Arner, P; Engfeldt, P; Haglund, K; Ostman, J; Rössner, S; Wahrenberg, H, 1985)	0.61
"Treatment with metoprolol (100 mg twice daily), nifedipine (10 mg 3 times daily) and both drugs combined were compared for effect on clinical variables, bicycle ergometer exercise tolerance and adverse effects in a randomized double-blind, crossover study in patients with stable effort angina (n = 62). "	( Metoprolol, nifedipine, and the combination in stable effort angina pectoris. Arstila, M; Bae, EA; Härkönen, R; Keyriläinen, O; Rytkönen, U; Schjelderup-Mathiesen, PM; Uusitalo, A; Wendelin, H, 1986)	2.07
"Treatment with metoprolol and combination therapy increased work performance."	( Hemodynamic effects of metoprolol and nifedipine in angina pectoris measured by isotope technique. Boström, PA, 1988)	0.93
"Treatment with metoprolol and nicardipine kept his blood pressure below 130/90 mm Hg while he was supine at rest and after walking."	( Spontaneous resolution of a dissection of the descending aorta after medical treatment with a beta blocker and a calcium antagonist. Hoshino, T; Ohmae, M; Sakai, A, 1987)	0.61
"Treatment with metoprolol of patients with a previously abnormal intravenous glucose tolerance test was not associated with a negative influence on the long-term prognosis."	( Effects of chronic metoprolol treatment on glucose tolerance after myocardial infarction. Olsson, G; Rehnqvist, N, 1987)	0.94

Excerpt	Reference	Relevance
" However, the combined administration could lead to adverse effects through amplification of negative inotropic and chronotropic properties."	( Acute hemodynamic and electrophysiologic effects and safety of high-dose intravenous diltiazem in patients receiving metoprolol. Kruijssen, DA; Look, MP; Remme, WJ; van Hoogenhuyze, DC; Wiesfeld, AC, 1992)	0.49
" Significantly fewer adverse events were experienced on lisinopril and metoprolol than on diuretic treatment."	( Quality of life, side effects and efficacy of lisinopril compared with metoprolol in patients with mild to moderate essential hypertension. Bech, P; Frimodt-Moeller, J; Kornerup, HJ; Poulsen, DL, 1991)	0.75
" Adverse reactions were experienced by 29% of the patients; most of these reactions were mild or moderate, and none was unexpected for treatment with a beta-blocker."	( Safety and tolerability of metoprolol OROS in hypertension treatment. Feliciano, N; Goldstein, RJ; Grau, KE; Hogan, LB; Kasarjian, PH; Kessler, C; McMillen, JI; Montoro, R; Mroczek, WJ; Stevelman, HB, 1990)	0.58
" No major adverse reactions related to the intervention were observed in either group."	( The safety of combined thrombolysis and beta-adrenergic blockade in patients with acute myocardial infarction. A randomized study. Lawson, WE; Vlay, SC, 1988)	0.27
" Except for one volunteer who complained of anxiety, weakness and sweating on the 6th day of cimetidine/metoprolol administration, no adverse effects could be observed during the combination therapy with cimetidine and the beta blockers or in monotherapy with beta blockers."	( Accumulation and adverse effects of metoprolol and propranolol after concurrent administration of cimetidine. Kirch, W; Köhler, H; Mutschler, E; Spahn, H, 1983)	0.76
" Since beta-blockers cross the placenta, it is essential to consider possible adverse effects on the embryo."	( Toxicity of beta-blockers in a rat whole embryo culture: concentration-response relationships and tissue concentrations. Klug, S; Merker, HJ; Neubert, D; Schwabe, R; Thiel, R, 1994)	0.29
" Thus, beta blockade may prove to be a safe and cost-effective bridge to transplantation."	( Safety and efficacy of beta blockade in patients with chronic congestive heart failure awaiting transplantation. Buchholz, C; Courtney, M; Gass, A; Kalman, J; Kukin, ML; Lansman, S; Steinmetz, M, )	0.13
" This approach does not necessarily detect the rare adverse events that may only be observed when very large numbers of patients are studied."	( Analysis of adverse effects among patients with essential hypertension receiving an ACE inhibitor or a beta-blocker. Bahrmann, H; Baumgart, P; Benkert, K; Bönner, G; Frohlich, ED; Klein, G; Neiss, A; Rosenthal, J; Schnelle, K, )	0.13
" Carvedilol low dose/high dose was shown to be at least as safe and well tolerated as metoprolol low dose/high dose both in younger and elderly patients."	( Comparison of safety and efficacy of carvedilol and metoprolol in stable angina pectoris. Griffiths, M; Hauf-Zachariou, U; Holtbrügge, W; König, S; Lahiri, A; Pfarr, E; van der Does, R, 1999)	0.78
"This study indicates that treatment with metoprolol succinate for a 6-month period is safe and well tolerated and is associated with an increase in left ventricular ejection fraction and a decrease in ventricular ectopic beats."	( Metoprolol CR/XL in patients with heart failure: A pilot study examining the tolerability, safety, and effect on left ventricular ejection fraction. Anderson, JL; Friday, G; Gheorghiade, M; Goldstein, S; Gottlieb, S; Hall, C; Haskell, L; Jessup, M; Karlsberg, RP; Kennedy, HL, 1999)	2.01
" Adverse effects resolved within 1 minute of dose reduction."	( Safety and tolerability of an aggressive tilt table test protocol in the evaluation of patients with suspected neurocardiogenic syncope. Brodsky, C; Vlay, LC; Vlay, SC, 2000)	0.31
" However, the impact of the CYP2D6 genotype on the occurrence of adverse effects of metoprolol remains controversial."	( Increased frequency of cytochrome P450 2D6 poor metabolizers among patients with metoprolol-associated adverse effects. Bergmann, K; Böhm, M; Eschenhagen, T; Heide, R; Rau, T; Weil, J; Werner, D; Wuttke, H, 2002)	0.77
"Approximately 1200 German physicians were asked to report on patients who had experienced pronounced adverse effects in association with administration of metoprolol."	( Increased frequency of cytochrome P450 2D6 poor metabolizers among patients with metoprolol-associated adverse effects. Bergmann, K; Böhm, M; Eschenhagen, T; Heide, R; Rau, T; Weil, J; Werner, D; Wuttke, H, 2002)	0.74
"These data showed that CYP2D6 poor metabolizers had a 5-fold higher risk for development of adverse effects during metoprolol treatment than patients who were not poor metabolizers."	( Increased frequency of cytochrome P450 2D6 poor metabolizers among patients with metoprolol-associated adverse effects. Bergmann, K; Böhm, M; Eschenhagen, T; Heide, R; Rau, T; Weil, J; Werner, D; Wuttke, H, 2002)	0.75
" Psoriasis may be an inconvenient side effect of beta blockade."	( Beta-blocker-induced psoriasis: a rare side effect--a case report. Akin, Y; Kisacik, HL; Korkmaz, S; Turhan, H; Yilmaz, MB, )	0.13
" The antiarrhythmics studied cause adverse reactions to the eye."	( Interaction of quinidine, disopyramide and metoprolol with melanin in vitro in relation to drug-induced ocular toxicity. Buszman, E; Rózańska, R, 2003)	0.58
" No adverse event was experienced."	( Metoprolol, a beta-1 selective blocker, can be used safely in coronary artery disease patients with chronic obstructive pulmonary disease. Akkuş, N; Alkan, M; Arikan, S; Avan, C; Aydoğdu, S; Camsari, A; Ciçek, D; Kaya, D; Kiykim, A; Pekdemir, H; Sezer, K, 2003)	1.76
"Beta-blockers substantially improve survival in patients with chronic heart failure (HF) with left ventricular systolic dysfunction, but concerns about cardiovascular adverse effects may deter physicians from prescribing this therapy."	( Adverse effects of beta-blocker therapy for patients with heart failure: a quantitative overview of randomized trials. Coffey, CS; Curtis, JP; Foody, JM; Hebert, PR; Ko, DT; Krumholz, HM; Sedrakyan, A, 2004)	0.32
" Metoprolol CR/XL was safe and well tolerated both during initiating therapy and during long-term follow-up."	( Efficacy, safety and tolerability of beta-adrenergic blockade with metoprolol CR/XL in elderly patients with heart failure. Deedwania, PC; Ghali, JK; Gottlieb, S; Waagstein, F; Wikstrand, JC, 2004)	1.47
"Metoprolol CR/XL was easily instituted, safe and well tolerated in elderly patients with systolic heart failure."	( Efficacy, safety and tolerability of beta-adrenergic blockade with metoprolol CR/XL in elderly patients with heart failure. Deedwania, PC; Ghali, JK; Gottlieb, S; Waagstein, F; Wikstrand, JC, 2004)	2
"Beta-Blocker use can be associated with adverse effects that may have an impact on adherence or harm patients."	( Pharmacokinetics and CYP2D6 genotypes do not predict metoprolol adverse events or efficacy in hypertension. Beitelshees, AL; Eberst, K; Gaedigk, A; Gelfand, CA; Johnson, JA; Leeder, JS; Pauly, DF; Phillips, MS; Walker, JR; Zineh, I, 2004)	0.57
" General and dose-limiting adverse events and blood pressure responses were analyzed in relation to metoprolol steady-state pharmacokinetic profile and CYP2D6 genotype-derived phenotype."	( Pharmacokinetics and CYP2D6 genotypes do not predict metoprolol adverse events or efficacy in hypertension. Beitelshees, AL; Eberst, K; Gaedigk, A; Gelfand, CA; Johnson, JA; Leeder, JS; Pauly, DF; Phillips, MS; Walker, JR; Zineh, I, 2004)	0.79
" Overall general and dose-limiting adverse event rates were 46% and 14%, respectively."	( Pharmacokinetics and CYP2D6 genotypes do not predict metoprolol adverse events or efficacy in hypertension. Beitelshees, AL; Eberst, K; Gaedigk, A; Gelfand, CA; Johnson, JA; Leeder, JS; Pauly, DF; Phillips, MS; Walker, JR; Zineh, I, 2004)	0.57
" However, there was no association between variable pharmacokinetics or CYP2D6 genotype and beta-blocker-induced adverse effects or efficacy."	( Pharmacokinetics and CYP2D6 genotypes do not predict metoprolol adverse events or efficacy in hypertension. Beitelshees, AL; Eberst, K; Gaedigk, A; Gelfand, CA; Johnson, JA; Leeder, JS; Pauly, DF; Phillips, MS; Walker, JR; Zineh, I, 2004)	0.57
" Adverse events were reported more often on placebo than on metoprolol CR/XL."	( Efficacy, safety and tolerability of metoprolol CR/XL in patients with diabetes and chronic heart failure: experiences from MERIT-HF. Deedwania, PC; Ghali, JK; Giles, TD; Herlitz, J; Hildebrandt, P; Kjekshus, J; Klibaner, M; Spinar, J; Stanbrook, H; Vitovec, J; Wikstrand, J, 2005)	0.84
"With appropriate protocol, MDCT is safe and accurate in assessing the severity of IRA and the number of diseased vessels during the first week after AMI."	( Safety and accuracy of multidetector row computed tomography for early assessment of residual stenosis of the infarct-related artery and the number of diseased vessels after acute myocardial infarction. Chiou, KR; Hsiao, SH; Liu, CP; Mar, GY; Pan, HB; Wu, MT; Yang, CF, 2005)	0.33
" The adverse effects studied comprised effects related to the central nervous system, cardiovascular effects, and sexual dysfunction."	( Impact of CYP2D6 genotype on adverse effects during treatment with metoprolol: a prospective clinical study. Delabar, U; Eichelbaum, M; Fux, R; Gleiter, CH; Kivistö, KT; Lorenz, G; Mörike, K; Pröhmer, AM; Schaeffeler, E; Schwab, M, 2005)	0.56
" Possible adverse effects of metoprolol were systematically assessed over a 6-week period by means of standardized rating scales and questionnaires."	( Impact of CYP2D6 genotype on adverse effects during treatment with metoprolol: a prospective clinical study. Delabar, U; Eichelbaum, M; Fux, R; Gleiter, CH; Kivistö, KT; Lorenz, G; Mörike, K; Pröhmer, AM; Schaeffeler, E; Schwab, M, 2005)	0.86
" There was no significant association between CYP2D6 genotype-derived phenotype (EMs and UMs combined versus PMs and IMs combined) and adverse effects during treatment with metoprolol."	( Impact of CYP2D6 genotype on adverse effects during treatment with metoprolol: a prospective clinical study. Delabar, U; Eichelbaum, M; Fux, R; Gleiter, CH; Kivistö, KT; Lorenz, G; Mörike, K; Pröhmer, AM; Schaeffeler, E; Schwab, M, 2005)	0.76
"CYP2D6 genotype-derived phenotype was not significantly associated with a propensity for adverse effects to develop during treatment with metoprolol."	( Impact of CYP2D6 genotype on adverse effects during treatment with metoprolol: a prospective clinical study. Delabar, U; Eichelbaum, M; Fux, R; Gleiter, CH; Kivistö, KT; Lorenz, G; Mörike, K; Pröhmer, AM; Schaeffeler, E; Schwab, M, 2005)	0.77
"5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects."	( Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling. Benz, RD; Contrera, JF; Kruhlak, NL; Matthews, EJ; Weaver, JL, 2004)	0.32
" There were no serious adverse events or adverse events requiring study drug discontinuation among patients receiving active therapy."	( Efficacy and safety of extended release metoprolol succinate in hypertensive children 6 to 16 years of age: a clinical trial experience. Batisky, DL; Falkner, B; Hainer, JW; Klibaner, M; Llewellyn, M; Portman, RJ; Sorof, JM; Sugg, J, 2007)	0.61
"Infusion dosage and timing, vital signs and adverse events."	( Safety of a postoperative beta-blocker infusion protocol for nonmonitored units in a community hospital. Atlas, S; Drury, J; Zarraga, I, 2007)	0.34
"A significant decrease in heart rate was demonstrated without any significant adverse events."	( Safety of a postoperative beta-blocker infusion protocol for nonmonitored units in a community hospital. Atlas, S; Drury, J; Zarraga, I, 2007)	0.34
"Our novel metoprolol infusion protocol was safe on nonmonitored units."	( Safety of a postoperative beta-blocker infusion protocol for nonmonitored units in a community hospital. Atlas, S; Drury, J; Zarraga, I, 2007)	0.74
" Number of patients reporting adverse effects (AEs) and severity of AEs in both of the groups were compared."	( Comparative clinical study of the efficacy and safety of a S-metoprolol ER tablet versus a racemate metoprolol ER tablet in patients with chronic stable angina. Aneja, P; Biswas, AD; Srinivas, A, 2007)	0.58
" The main adverse event related to Felodipine was headache, and to Lisinopril was cough."	( [Efficacy, safety and tolerance of Felodipine controlled release tablets and Felodipine controlled release tablets associated combination therapy in the treatment of mild to moderate essential hypertension in China]. Chen, YY; Liu, HL; Shen, FR; Sun, NL; Tao, J; Wu, HY; Xiang, XP; Yu, ZQ; Zhang, FC; Zhang, L; Zhang, WZ; Zhao, JA, 2007)	0.34
" No adverse events resulted from rate control medication."	( Safety and efficacy of a rate control protocol for cardiac CT. Roberts, WT; Timmis, AD; Timmis, JB; Wright, AR, 2009)	0.35
"The total response rate of amiodarone does not seem to be superior to metoprolol in the treatment of premature ventricular contractions, and amiodarone is associated with higher incidence of adverse reactions."	( [Efficacy and safety of amiodarone and metoprolol in the treatment of ventricular premature beats: a meta-analysis]. Huang, ZJ; Li, T; Li, YL; Wu, YL; Yang, MQ, 2010)	0.86
" Moreover, toxic effects obtained at high dose level of each treatment groups were transient and reversible and no evidence of additive toxic effects were observed due to concomitant administration."	( Pharmacokinetics, pharmacodynamics and toxicity of a combination of metoprolol succinate and telmisartan in Wistar albino rats: safety profiling. Chatterjee, N; Das, AK; Ghosh, B; Karmakar, S; Nandi, U; Padman, A; Pal, TK, 2013)	0.63
" The most pronounced and selective toxic action of MET and products of its photodegradation was observed in the hepatic cell line."	( Toxicity assessment of metoprolol and its photodegradation mixtures obtained by using different type of TiO2 catalysts in the mammalian cell lines. Abramović, BF; Armaković, SJ; Četojević-Simin, DD; Šojić, DV, 2013)	0.7
" The results indicate that the oxidative treatment (O3 or UV/H2O2) of Bisphenol A, Metoprolol, Sulfamethoxazole or Ciprofloxacin in waste water did not result in toxic oxidation by-products, whereas the UV/H2O2 treatment of Bisphenol A and Ciprofloxacin in pure water resulted in by-products with cytotoxic but no estrogenic effects after 60min."	( Toxicity of the micropollutants Bisphenol A, Ciprofloxacin, Metoprolol and Sulfamethoxazole in water samples before and after the oxidative treatment. Bester, K; Boergers, A; Richard, J; Tuerk, J; Vom Eyser, C, )	0.6
" Even though BB are safe for human and veterinary usage, ecosystems may be exposed to these substances."	( Beta-blockers in the environment: part II. Ecotoxicity study. Białk-Bielińska, A; Caban, M; Kumirska, J; Maszkowska, J; Mioduszewska, K; Puckowski, A; Stepnowski, P; Stolte, S; Wagil, M; Łukaszewicz, P, 2014)	0.4
"5 hours of symptom onset in our subjects reduced infarct size and improved left ventricular ejection fraction with no excess of adverse events during the first 24 hours."	( Efficacy and safety of out-of-hospital intravenous metoprolol administration in anterior ST-segment elevation acute myocardial infarction: insights from the METOCARD-CNIC trial. Barreiro, MV; Bravo, J; Chayán-Zas, L; Corral, E; Fernández-Friera, L; Fernández-Jiménez, R; Flores-Arias, J; Fuster, V; García-Álvarez, A; García-Lunar, I; García-Ruiz, JM; Huertas, P; Ibáñez, B; Mateos, A; Pizarro, G; Sánchez-Brunete, V, 2015)	0.67
"A retrospective analysis of scan reports and hospital admissions data was conducted to identify adverse events occurring following CT coronary angiography in patients who had received intravenous metoprolol prior to the scan."	( Safety of intravenous β-adrenoceptor blockers for computed tomographic coronary angiography. Clayton, B; Morgan-Hughes, G; Raju, V; Roobottom, C, 2015)	0.61
" There was a single adverse incident, comprising transient loss of consciousness."	( Safety of intravenous β-adrenoceptor blockers for computed tomographic coronary angiography. Clayton, B; Morgan-Hughes, G; Raju, V; Roobottom, C, 2015)	0.42
" The primary outcome measure was the rate of serious adverse events (SAE), defined as a complication of intravenous metoprolol resulting in transfer to a critical-care environment, a medical emergency team call or death."	( Safety of intravenous metoprolol use in unmonitored wards: a single-centre observational study. Barrett, J; Cunningham, M; Hawdon, G; Kelly, D; Morris, A; Reeves, J, 2015)	0.94
"Many adverse drug reactions are caused by the cytochrome P450 (CYP)-dependent activation of drugs into reactive metabolites."	( Development of a cell viability assay to assess drug metabolite structure-toxicity relationships. Jones, LH; Nadanaciva, S; Rana, P; Will, Y, 2016)	0.43
" Adverse events were registered in 10 of 61 and 7 of 59 patients (16."	( [Comparative Assessment of Antianginal Efficacy and Safety of Nicorandil at the Background of Therapy With -Adrenoblockers in Ischemic Heart Disease Patients With Stable Angina]. Deev On Behalf Of The Kvazar Study, AD; Kutishenko, NP; Martsevitch, SY, 2016)	0.43
"Clinical efficacy and adverse effects of the β-blocking agents, carvedilol, bisoprolol, and metoprolol were analyzed theoretically, and then compared quantitatively, for the purpose of determining their proper use for chronic heart failure."	( Analysis of Clinical Efficacy and Adverse Effects of β-Blocking Agents Used Clinically for Chronic Heart Failure. Fujito, K; Kimura, K; Takayanagi, R; Yamada, Y, 2017)	0.68
"Acute severe hypertension occurs infrequently in pediatric patients and, consequently, data on the efficacy and safety of most antihypertensive agents, as well as the adverse events associated with these agents, are very limited in this population."	( Evaluation of the safety and efficacy of metoprolol infusion for children and adolescents with hypertensive crises: a retrospective case series. Saqan, R; Thiabat, H, 2017)	0.72
"An infusion of metoprolol for a hypertensive emergency is a safe and effective treatment for pediatric patients."	( Evaluation of the safety and efficacy of metoprolol infusion for children and adolescents with hypertensive crises: a retrospective case series. Saqan, R; Thiabat, H, 2017)	1.07
" Secondary: changes of a) LV-FS from baseline, b) blood pressure, c), heart rate and autonomic function in ECG and Holter-ECG, e) cardiac biomarkers and neurohumeral serum parameters, f) quality of life, and g) adverse events."	( Effect and safety of treatment with ACE-inhibitor Enalapril and β-blocker metoprolol on the onset of left ventricular dysfunction in Duchenne muscular dystrophy - a randomized, double-blind, placebo-controlled trial. Dittrich, S; Ebinger, F; Graf, E; Heilmann, A; Khalil, M; Kirschner, J; Korenke, C; Lange, M; Motz, R; Müller-Felber, W; Neudorf, U; Pattathu, J; Pozza, RD; Schara, U; Schröder, R; Stiller, B; Trollmann, R; von Au, K; von der Hagen, M; Weiss, K; Wiechmann, N; Wilichowski, E, 2019)	0.74
" As a single, yet important adverse event, the reversible deterioration of walking abilities of one DMD patient during the run-in period was observed."	( Effect and safety of treatment with ACE-inhibitor Enalapril and β-blocker metoprolol on the onset of left ventricular dysfunction in Duchenne muscular dystrophy - a randomized, double-blind, placebo-controlled trial. Dittrich, S; Ebinger, F; Graf, E; Heilmann, A; Khalil, M; Kirschner, J; Korenke, C; Lange, M; Motz, R; Müller-Felber, W; Neudorf, U; Pattathu, J; Pozza, RD; Schara, U; Schröder, R; Stiller, B; Trollmann, R; von Au, K; von der Hagen, M; Weiss, K; Wiechmann, N; Wilichowski, E, 2019)	0.74
"Real-world spontaneous adverse event reports and administrative health care data were utilized as one part of a multipronged approach to verify surveillance signals related to generic drug formulations."	( Real-World Data Approaches for Early Detection of Potential Safety and Effectiveness Signals for Generic Substitution: A Metoprolol Extended-Release Case Study. Brown, JD; Henriksen, C; Schmidt, S; Vozmediano, V, 2019)	0.72
"Provide a safe and efficient metoprolol dose protocol to be used in pediatric outpatients undergoing CCTA."	( Safety, Efficacy, and Dose Protocol of Metoprolol for Heart Rate Reduction in Pediatric Outpatients Undergoing Cardiac CT Angiography. Casey, SA; Caye, DJ; Han, BK; J Chu, B; Lesser, JR; Lindberg, BJ; Nunes, MO; Stanberry, LI; Witt, DR, 2021)	1.18
" No complications or adverse events were reported."	( Safety, Efficacy, and Dose Protocol of Metoprolol for Heart Rate Reduction in Pediatric Outpatients Undergoing Cardiac CT Angiography. Casey, SA; Caye, DJ; Han, BK; J Chu, B; Lesser, JR; Lindberg, BJ; Nunes, MO; Stanberry, LI; Witt, DR, 2021)	0.89
"Use of metoprolol in a pediatric outpatient setting for HR reduction prior to CCTA is safe and effective."	( Safety, Efficacy, and Dose Protocol of Metoprolol for Heart Rate Reduction in Pediatric Outpatients Undergoing Cardiac CT Angiography. Casey, SA; Caye, DJ; Han, BK; J Chu, B; Lesser, JR; Lindberg, BJ; Nunes, MO; Stanberry, LI; Witt, DR, 2021)	1.35
" This data suggest that intravitreal metoprolol may be a safe alternative for cCSC."	( Safety of intravitreal metoprolol in eyes with central serous chorioretinopathy. Chaves, L; de Azeredo Bastos, TM; Gonçalves, AN; Jorge, R; Messias, A, 2022)	1.3

Excerpt	Reference	Relevance
" Plasma levels of the drugs were also determined in order to calculate certain pharmacokinetic variables."	( Haemodynamic effects and pharmacokinetics of a new selective beta1-adrenoceptor agonist, prenalterol, and its interaction with metoprolol in man. Graffner, C; Johnsson, G; Jordö, L; Lundborg, P; Rönn, O; Wikstrand, J, 1979)	0.47
" Extensive and poor metabolizers after oral administrations of slow-release metoprolol tablets were classified by means of the frequency distribution of Cmax values."	( Variation of pharmacokinetics after oral administration of slow-release metoprolol tablets and pharmacogenetic considerations. Noguchi, H; Shimizu, H; Uno, K, 1992)	0.75
" There is evidence that the pharmacokinetics of metoprolol in the goat occurs stereoselectively and that enantiomer-enantiomer pharmacokinetic interactions occur."	( Rapid chiral separation of metoprolol in plasma--application to the pharmacokinetics/pharmacodynamics of metoprolol enantiomers in the conscious goat. Leloux, MS, )	0.68
" By using pharmacokinetic pharmacodynamic modeling the pharmacodynamics of racemic metoprolol and the active S-isomer, were quantitated in EMs and PMs in terms of IC50 values, representing metoprolol plasma concentrations resulting in half-maximum receptor occupancy."	( Debrisoquine phenotype and the pharmacokinetics and beta-2 receptor pharmacodynamics of metoprolol and its enantiomers. Jonkers, RE; Koopmans, RP; Portier, EJ; van Boxtel, CJ, 1991)	0.73
" This review describes the biopharmaceutical and pharmacokinetic properties of metoprolol CR/ZOK, a recently introduced formulation of a widely used beta 1-selective adrenoceptor antagonist intended for once daily usage."	( Pharmacokinetic and biopharmaceutic aspects of once daily treatment with metoprolol CR/ZOK: a review article. Abrahamsson, B; Bergstrand, R; Regårdh, CG; Sandberg, A; Wieselgren, I, 1990)	0.74
" The terminal plasma half-life (t1/2) on day 29 was 22 hours and systemic clearance was 490 mL/min on day 1 and 434 mL/min on day 29 (NS)."	( Acute and steady-state pharmacokinetics and antihypertensive effects of felodipine in patients with normal and impaired renal function. Aberg, J; Gelin, A; Karlberg, BE; Larsson, R; Regårdh, CG, 1990)	0.28
" The plasma concentration-time profile following metoprolol CR/ZOK 50 mg administration was more even compared to conventional metoprolol tablets, with significantly lower Cmax (mean: 71 vs 221 nmol/L) and significantly higher Cmin (mean: 39 vs 6 nmol/L) for the CR/ZOK formulation."	( Pharmacokinetic and pharmacodynamic evaluation of metoprolol controlled release (CR/ZOK) 50 mg in young subjects. Bergstrand, R; Lundborg, P; Olofsson, B; Sandberg, A; Wieselgren, I, 1990)	0.79
" The pharmacokinetic differences between the formulations also produced differences in the time profiles of exercise heart rate."	( A pharmacokinetic and pharmacodynamic comparison of metoprolol CR/ZOK with a conventional slow release preparation. Jonkman, J; Oosterhuis, B; Sollie, F; Zuiderwijk, P, 1990)	0.53
"Four double-blind, Latin-square studies were conducted to compare the pharmacokinetics and pharmacodynamic bioavailability of metoprolol OROS (oral osmotic) and the conventional tablet (CT) of metoprolol."	( Pharmacokinetic and pharmacodynamic comparison of an osmotic release oral metoprolol tablet and the metoprolol conventional tablet. Arnold, JD; Bouvet, AA; Castellana, J; Feliciano, NR; Leese, PT; Luders, RC; Redalieu, E; Schwartz, DJ; Shum, L; Zak, S, 1990)	0.72
" There was a significant decrease in the maximal plasma concentration and AUC of metoprolol after 28 days of treatment with felodipine, but its elimination half-life was not changed."	( Haemodynamic effects and pharmacokinetics of felodipine at rest and during exercise in hypertensive patients treated with metoprolol or atenolol. Bengtsson-Hasselgren, B; Elmfeldt, D; Moberg, L; Rönn, O, 1989)	0.71
"Comparative pharmacokinetic studies with the beta-receptor blocking drugs propranolol, metoprolol, sotalol and atenolol, differing greatly in lipophilicity, and their main route of elimination were performed in light-dark-synchronized rats after equimolar single (6 mumoles/kg) or multiple (6 X 6 mumoles/kg) drug application."	( Chronopharmacokinetics of beta-receptor blocking drugs of different lipophilicity (propranolol, metoprolol, sotalol, atenolol) in plasma and tissues after single and multiple dosing in the rat. Fink, M; Lemmer, B; Ohm, T; Winkler, H, 1985)	0.71
" The poor metaboliser phenotype is associated with increased plasma drug concentrations, a prolongation of elimination half-life and more intense and sustained beta-blockade."	( The polymorphic oxidation of beta-adrenoceptor antagonists. Clinical pharmacokinetic considerations. Lennard, MS; Tucker, GT; Woods, HF, )	0.13
"The pharmacodynamic profile of bisoprolol, a new beta 1-selective adrenoceptor antagonist, was investigated in four independent studies including 36 healthy male volunteers."	( Pharmacodynamic profile of bisoprolol, a new beta 1-selective adrenoceptor antagonist. Bühring, KU; Leopold, G; Pabst, J; Simane, Z; Ungethüm, W; Wiemann, H, 1986)	0.27
" Betaxolol (Kerlon, 8) was found to exhibit an appropriate preclinical pharmacological and human pharmacokinetic profile (elevated oral bioavailability and prolonged plasma half-life) for the treatment of chronic cardiovascular diseases such as hypertension and angina."	( Synthesis of a series of compounds related to betaxolol, a new beta 1-adrenoceptor antagonist with a pharmacological and pharmacokinetic profile optimized for the treatment of chronic cardiovascular diseases. Binet, JL; Cavero, IG; Lefèvre-Borg, F; Manoury, PM; Rousseau, J, 1987)	0.27
" These pharmacokinetic differences between metoprolol CR and metoprolol SR produced a different duration of clinically relevant beta 1-blockade, defined as a reduction in exercise heart rate of greater than 10%."	( Pharmacokinetic and pharmacodynamic comparison of a new controlled-release formulation of metoprolol with a traditional slow-release formulation. Jonkman, JH; Kerkhof, FA; Oosterhuis, B, 1988)	0.76
"Pharmacokinetic and pharmacodynamic properties of a new controlled-release (CR) formulation of metoprolol have been compared with those of atenolol."	( Pharmacokinetics and pharmacodynamics of controlled-release metoprolol: a comparison with atenolol. Blomqvist, I; Jonsson, UE; Lundborg, P; Sandberg, A; Westergren, G, 1988)	0.74
"The pharmacokinetic and pharmacodynamic properties of a new multiple-unit, controlled-release (CR) formulation of metoprolol (metoprolol succinate, 95 mg once daily), which has almost constant (zero-order) release properties over most of a 24-h dose interval, have been compared with those of conventional metoprolol tablets (metoprolol tartrate, 100 mg once daily and 50 mg twice daily), in 12 healthy male volunteers."	( Pharmacokinetic and pharmacodynamic properties of a new controlled-release formulation of metoprolol: a comparison with conventional tablets. Blomqvist, I; Jonsson, UE; Lundborg, P; Sandberg, A, 1988)	0.71
"The pharmacokinetic basis for using various experimental indices, (urinary drug: metabolite and metabolite:drug + metabolite ratios, urinary metabolite recovery and AUC values), for detecting polymorphic oxidative drug metabolism was examined."	( Polymorphic drug oxidation: pharmacokinetic basis and comparison of experimental indices. Jackson, PR; Lennard, MS; Tucker, GT; Woods, HF, 1986)	0.27
" There was at least a 7-day washout period between each pharmacokinetic study day."	( Pharmacokinetic interactions between felodipine and metoprolol. Jack, DB; Kendall, MJ; Laugher, S; Smith, SR; Wilkins, MR, 1987)	0.52
"1 The speed of onset of the pharmacodynamic activity of intravenous propranolol, practolol, oxprenolol and metoprolol was determined, using attenuation of isoprenaline-induced tachycardia as the end-point, in 16 patients with clinically coronary heart disease."	( Speed of onset of pharmacodynamic activity of propranolol, practolol, oxprenolol and metoprolol after intravenous infection in man. Lochan, R; Silke, B; Taylor, SH, 1981)	0.7
" Metoprolol is affected by hydralazine, the AUC and Cmax being significantly increased."	( The effect of hydralazine on the pharmacokinetics of three different beta adrenoceptor antagonists: metoprolol, nadolol, and acebutolol. Dean, S; Jack, DB; Kendall, MJ; Laugher, SJ; Tenneson, ME; Zaman, R, )	1.26
" The present study did not show significant pharmacokinetic and pharmacodynamic interactions between nifedipine and lipophilic beta-adrenoceptor blockers."	( Study of the influence of nifedipine on the pharmacokinetics and pharmacodynamics of propranolol, metoprolol and atenolol. Bellens, R; Degre, S; Degreve, M; Fitzsimons, TJ; Gangji, D; Herchuelz, A; Juvent, M; Niset, G; Poortmans, J; Wathieu, M, 1984)	0.48
" The study reported here was designed to show whether the pharmacokinetics of verapamil are influenced by concurrent treatment with three different beta-adrenoceptor blockers, and whether there is any pharmacodynamic interaction between these drugs."	( Pharmacokinetics and pharmacodynamics of verapamil in combination with atenolol, metoprolol and propranolol. Fitzsimons, TJ; Holt, D; Johnston, A; Warrington, SJ, 1984)	0.49
"Higher AUC and Cmax values were obtained for metoprolol, oxprenolol and propranolol in groups receiving the low-dose oestrogen-ethinyl oestradiol oral contraceptive, but statistical significance was reached only with metoprolol AUC."	( Beta-adrenoceptor blocker pharmacokinetics and the oral contraceptive pill. Jack, DB; Kendall, MJ; Quarterman, CP; Smith, SR; Zaman, R, 1984)	0.53
" Plasma and urine drug concentrations were measured and the relevant pharmacokinetic parameters calculated."	( Lack of a pharmacokinetic interaction between nifedipine and the beta-adrenoceptor blockers metoprolol and atenolol. Jack, DB; Kendall, MJ; Laugher, SJ; Lobo, J; Rolf Smith, S, 1984)	0.49
" With the exception of the volume term, V beta, the pharmacokinetic parameters were not significantly different between the elderly and the young individuals."	( Pharmacokinetics of metoprolol in healthy, elderly, non-smoking individuals after a single dose and two weeks of treatment. Landahl, S; Larsson, M; Lundborg, P; Regårdh, CG, 1984)	0.59
"In 6 normotensive, healthy male volunteers the pharmacodynamic responses (blood pressure, heart rate; sedation index, tracking test, reaction time) to metoprolol (100 mg bid orally), diazepam (0."	( Pharmacokinetic and pharmacodynamic interaction study of diazepam and metoprolol. Klotz, U; Reimann, IW, 1984)	0.7
" The elimination half-life of atenolol, about 10 h, was not affected by the health status of the subjects."	( Influence of inflammatory disease on the clinical pharmacokinetics of atenolol and metoprolol. Heinz, U; Kirch, W; Köhler, H; Mutschler, E; Ohnhaus, EE; Spahn, H, )	0.36
" The volume of distribution, elimination half-life and total body clearance were almost the same as previously observed in healthy, young subjects."	( Pharmacokinetics of metoprolol and its metabolite alpha-OH-metoprolol in healthy, non-smoking, elderly individuals. Hoffmann, KJ; Lagerström, PO; Landahl, S; Larsson, M; Lundborg, P; Regårdh, CG; Steen, B, 1983)	0.59
"A potential pharmacokinetic interaction between the beta-blocking drug, metoprolol, and the diuretic, chlorthalidone, has been investigated in three single or multiple dose studies in healthy volunteers."	( Comparative pharmacokinetic profiles of metoprolol and chlorthalidone administered alone or in combination to healthy volunteers. Gerardin, A; Godbillon, J; John, VA; Theobald, W, 1983)	0.77
" 3 Areas under the plasma concentration curve for metoprolol after repeated administration are greater than would be predicted from single dose data, and possible explanations for this are discussed."	( The effect of age on the pharmacokinetics of metoprolol and its metabolites. Jack, DB; Kendall, MJ; Quarterman, CP, 1981)	0.78
"Pharmacokinetic and pharmacodynamic profiles for metoprolol have been measured in six healthy volunteers after single and multiple dosing with 100 mg conventional formulation twice daily and 200 mg slow-release formulation once daily."	( A single and multiple dose pharmacokinetic and pharmacodynamic comparison of conventional and slow-release metroprolol. John, VA; Kendall, MJ; Quarterman, CP; Welling, PG, 1980)	0.52
"The bioavailability and pharmacodynamic bioequivalence of a conventional and an experimental sustained-release formulation of 100 mg metoprolol tartrate were studied in a randomised cross-over study in seven healthy volunteers by assessing over 24 h the plasma kinetics of R,S-metoprolol, its beta 1-adrenoceptor binding component, and by determining the extent to which the active drug moiety in plasma occupied rabbit lung beta 1- and rat reticulocyte beta 2-adrenoceptors."	( Receptor binding assays in analysing the bioavailability and pharmacodynamic bioequivalence of active drug moieties. A study of metoprolol. Kaila, T; Neuvonen, PJ; Roivas, L, 1994)	0.7
" The controlled-release formulation gave less variable plasma metoprolol concentrations, Cmax 138 nmol."	( The pharmacokinetics and pharmacodynamics of metoprolol after conventional and controlled-release administration in combination with hydrochlorothiazide in healthy volunteers. Abrahamsson, B; Lundborg, P; Walter, M; Wieselgren, I, 1993)	0.79
"Single and repeated oral doses pharmacokinetic studies of metoprolol sustained-release tablets (Sino-Swed Pharmaceutical Co Ltd) were performed on 12 Chinese healthy subjects in an open randomized crossover manner, using metoprolol tablets from Sweden Astra International Pharmaceutical Co Ltd as control."	( Pharmacokinetics of sustained-release tablets of metoprolol in Chinese. Diao, Y; Li, L, 1993)	0.78
" administration of racemic metoprolol in the rat, the plasma concentrations of (R)- and (S)-metoprolol were comparable, and no differences in pharmacokinetic parameters between the two enantiomers were found."	( Aging and the pharmacokinetics and metabolism of metoprolol enantiomers in the rat. Belpaire, FM; Bogaert, MG; De Smet, F; Vercruysse, I; Vermeulen, AM, 1993)	0.84
" The primary pharmacokinetic characteristics for extent and rate of absorption were AUC(0-24h) and % PTF, respectively."	( Pantoprazole has no influence on steady state pharmacokinetics and pharmacodynamics of metoprolol in healthy volunteers. Bliesath, H; Hartmann, M; Huber, R; Koch, HJ; Mascher, H; Steinijans, VW; Wurst, W, 1996)	0.52
" The pharmacokinetic analysis included enantioselective analysis in six subjects."	( Bioequivalence, pharmacokinetic and pharmacodynamic response to combined extended release formulations of felodipine and metoprolol in healthy volunteers. Aberg, J; Abrahamsson, B; Grind, M; Nyberg, G; Olofsson, B, 1997)	0.5
"Bioequivalence between the fixed combination and the free combination was observed for the two drugs (mean difference 27%) except for a minor deviation regarding Cmax of metoprolol in the elderly."	( Bioequivalence, pharmacokinetic and pharmacodynamic response to combined extended release formulations of felodipine and metoprolol in healthy volunteers. Aberg, J; Abrahamsson, B; Grind, M; Nyberg, G; Olofsson, B, 1997)	0.7
" Finally, felodipine and metoprolol do not interact on a pharmacokinetic level when administered as the fixed combination."	( Bioequivalence, pharmacokinetic and pharmacodynamic response to combined extended release formulations of felodipine and metoprolol in healthy volunteers. Aberg, J; Abrahamsson, B; Grind, M; Nyberg, G; Olofsson, B, 1997)	0.81
" Pharmacokinetic parameters were determined for each subject and statistically compared in two groups of 16 homozygous (CYP2D61/CYP2D61) and six heterozygous (CYP2D61/CYP2D64) volunteers."	( Influence of the cytochrome P4502D6*4 allele on the pharmacokinetics of controlled-release metoprolol. Alken, RG; Kaneva, R; Kirkov, V; Koytchev, R; Rehak, E; Thyroff-Friesinger, U; Vlahov, V, 1998)	0.52
"Significant differences between homozygous and heterozygous individuals were observed for all pharmacokinetic parameters."	( Influence of the cytochrome P4502D6*4 allele on the pharmacokinetics of controlled-release metoprolol. Alken, RG; Kaneva, R; Kirkov, V; Koytchev, R; Rehak, E; Thyroff-Friesinger, U; Vlahov, V, 1998)	0.52
" No statistically significant difference was observed between the logarithmically transformed AUC0-infinity values or the logarithmically transformed Cmax values of the two preparations."	( Pharmacokinetic and bioequivalent study of a generic Metoprolol tablet preparation. Chan, KL; Peh, KK; Toh, WT; Yuen, KH, 1998)	0.55
" The pharmacokinetic parameters and the PK-PD model parameters were calculated."	( Pharmacokinetic-pharmacodynamic modeling of metoprolol stereoisomers in spontaneously hypertensive rat. Ding, Y; Huang, DK; Huang, XP; Luo, JP; Shen, JP; Yin, XX; Zhang, YD, 1997)	0.56
" Subjects also completed a control pharmacodynamic study; the order of drug and control studies was randomized."	( Gender-related effects on metoprolol pharmacokinetics and pharmacodynamics in healthy volunteers. Forrest, A; Kazierad, DJ; Killian, A; Luzier, AB; Wilson, MF; Wilton, JH, 1999)	0.6
" Pharmacodynamic data were best fitted by the Hill equation with the effect site in the central compartment."	( Gender-related effects on metoprolol pharmacokinetics and pharmacodynamics in healthy volunteers. Forrest, A; Kazierad, DJ; Killian, A; Luzier, AB; Wilson, MF; Wilton, JH, 1999)	0.6
" The methods were employed to determine plasma concentrations of metoprolol enantiomers in a pharmacokinetic study of single dose administration of racemic metoprolol to a healthy Caucasian volunteer phenotyped as extensive metabolizer of debrisoquine."	( Enantioselective analysis of metoprolol in plasma using high-performance liquid chromatographic direct and indirect separations: applications in pharmacokinetics. Bonato, PS; Cerqueira, PM; Cesarino, EJ; Lanchote, VL; Pereira, VA, 2000)	0.84
" Enantiomer Cmax and AUC prediction errors (PEs) were estimated for model evaluation after convolution of in vivo release rates."	( Influence of stereoselective pharmacokinetics in the development and predictability of an IVIVC for the enantiomers of metoprolol tartrate. Eddington, ND; Sirisuth, N, 2000)	0.52
"The R-IVIVC and S-IVIVC accurately predicted the R- and S-metoprolol pharmacokinetic profiles, respectively."	( Influence of stereoselective pharmacokinetics in the development and predictability of an IVIVC for the enantiomers of metoprolol tartrate. Eddington, ND; Sirisuth, N, 2000)	0.76
" A secondary aim was to relate the efficacy of the free and fixed combinations with pharmacokinetic profiles."	( The pharmacodynamic and pharmacokinetic profiles of controlled-release formulations of felodipine and metoprolol in free and fixed combinations in elderly hypertensive patients. Elliott, HL; Hosie, J; MacDonald, TM; McLay, JS, 2000)	0.52
" Pharmacokinetic evaluation revealed identical plasma concentration-time curves for felodipine given as the free or fixed combination."	( The pharmacodynamic and pharmacokinetic profiles of controlled-release formulations of felodipine and metoprolol in free and fixed combinations in elderly hypertensive patients. Elliott, HL; Hosie, J; MacDonald, TM; McLay, JS, 2000)	0.52
" The present studies investigated the potential for pharmacokinetic or pharmacodynamic interaction between beta-adrenoceptor blockers and rizatriptan."	( Influence of beta-adrenoceptor antagonists on the pharmacokinetics of rizatriptan, a 5-HT1B/1D agonist: differential effects of propranolol, nadolol and metoprolol. De Smet, M; Goldberg, MR; Halpin, R; James, I; Kari, PH; Lee, Y; Lowry, R; Olah, TV; Sciberras, D; Tomasko, L; Vyas, KP; Zhao, J, 2001)	0.51
"5 days) increased the AUC(0, infinity) for rizatriptan by approximately 67% and the Cmax by approximately 75%."	( Influence of beta-adrenoceptor antagonists on the pharmacokinetics of rizatriptan, a 5-HT1B/1D agonist: differential effects of propranolol, nadolol and metoprolol. De Smet, M; Goldberg, MR; Halpin, R; James, I; Kari, PH; Lee, Y; Lowry, R; Olah, TV; Sciberras, D; Tomasko, L; Vyas, KP; Zhao, J, 2001)	0.51
" As a class, the beta blockers are quite diverse from a pharmacokinetic perspective, as they display a high range of values in plasma protein binding, percent of drug eliminated by metabolism or unchanged in the urine, and in hepatic extraction ratio."	( Stereospecific pharmacokinetics and pharmacodynamics of beta-adrenergic blockers in humans. Brocks, DR; Mehvar, R, )	0.13
" The confident limits show that the methods are compatible with pharmacokinetic investigations of the enantioselective metabolism of metoprolol."	( Enantioselective determination of metoprolol acidic metabolite in plasma and urine using liquid chromatography chiral columns: applications to pharmacokinetics. Bonato, PS; Boralli, VB; Cerqueira, PM; Coelho, EB; Guimarães, LF; Lanchote, VL; Lopes, NP, 2003)	0.8
" Pharmacokinetic studies have also been performed in heart failure patients and have demonstrated that ER metoprolol succinate is associated with a more pronounced and even beta1-blockade over a 24-h period than the IR formulation."	( Pharmacokinetic considerations of formulation: extended-release metoprolol succinate in the treatment of heart failure. Andersson, B; Kendall, MJ; Klibaner, M; Stanbrook, H; Wikstrand, J, 2003)	0.77
" The pharmacokinetic parameters of metoprolol in individual patients were obtained from population estimates according to Bayes' theorem."	( Effect of CYP2D6*10 on pharmacokinetic variability of routinely administered metoprolol in middle-aged and elderly Japanese patients. Hashimoto, Y; Inoue, H; Kameyama, T; Mizukami, A; Nozawa, T; Taguchi, M; Takesono, C, 2003)	0.82
"The present study indicated that CYP2D6*10 is mainly responsible for the large pharmacokinetic variability of routinely administered metoprolol in middle-aged and elderly Japanese patients."	( Effect of CYP2D6*10 on pharmacokinetic variability of routinely administered metoprolol in middle-aged and elderly Japanese patients. Hashimoto, Y; Inoue, H; Kameyama, T; Mizukami, A; Nozawa, T; Taguchi, M; Takesono, C, 2003)	0.75
" Pharmacokinetic parameters of metoprolol were investigated at day 5 and at day 13 in 44 subjects, 39 extensive metabolizers and five poor metabolizers for CYP2D6."	( Pharmacokinetic and pharmacodynamic interactions between metoprolol and dronedarone in extensive and poor CYP2D6 metabolizers healthy subjects. Caplain, H; Damy, T; Hulot, JS; Lechat, P; Pousset, F, 2004)	0.85
" A comparison is also presented between several methods based on animal pharmacokinetic data, using the same set of proprietary compounds, and it lends further support for the use of this method, as opposed to methods that require the gathering of pharmacokinetic data in laboratory animals."	( Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics. Gao, F; Lombardo, F; Obach, RS; Shalaeva, MY, 2004)	0.32
"The present study addressed possible alterations in the pharmacodynamic and pharmacokinetic properties of the beta1-adrenoceptor antagonist metoprolol in experimental hypertension induced by abdominal aortic coarctation (ACo)."	( Pharmacokinetic-pharmacodynamic properties of metoprolol in chronic aortic coarctated rats. Di Verniero, C; Höcht, C; Opezzo, JA; Taira, CA, 2004)	0.78
"The objective of the present study is to carry out pharmacokinetic evaluation of oral controlled release formulation (guar gum-based three-layer matrix tablets) containing highly soluble metoprolol tartrate as a model drug."	( Pharmacokinetic evaluation of guar gum-based three-layer matrix tablets for oral controlled delivery of highly soluble metoprolol tartrate as a model drug. Al-Saidan, SM; Bhaskar, P; Karthikeyan, RS; Krishnaiah, YS; Satyanarayana, V, 2004)	0.72
"This study was performed to estimate the mean pharmacokinetic parameters of routinely administered metoprolol in middle-aged and elderly Japanese patients."	( Nonlinear mixed effects model analysis of the pharmacokinetics of metoprolol in routinely treated Japanese patients. Hashimoto, Y; Inoue, H; Mizumaki, K; Nozawa, T; Taguchi, M; Tahara, K; Takesono, C, 2004)	0.78
"Beta-blockers differ in their pharmacokinetic and pharmacodynamic properties."	( Pharmacokinetics and pharmacodynamics of beta blockers in heart failure. Talbert, RL, 2004)	0.32
" General and dose-limiting adverse events and blood pressure responses were analyzed in relation to metoprolol steady-state pharmacokinetic profile and CYP2D6 genotype-derived phenotype."	( Pharmacokinetics and CYP2D6 genotypes do not predict metoprolol adverse events or efficacy in hypertension. Beitelshees, AL; Eberst, K; Gaedigk, A; Gelfand, CA; Johnson, JA; Leeder, JS; Pauly, DF; Phillips, MS; Walker, JR; Zineh, I, 2004)	0.79
" In vivo pharmacokinetic and in vitro metabolic studies were conducted using metoprolol and propranolol, which show substantial and marginal polymorphisms in humans, respectively."	( Pharmacokinetics and metabolism of metoprolol and propranolol in the female DA and female Wistar rat: the female DA rat is not always an animal model for poor metabolizers of CYP2D6. Iwaki, M; Komura, H, 2005)	0.83
" Furthermore, the over-the-counter antihistamine diphenhydramine inhibited the metabolism of the CYP2D6 substrate metoprolol in healthy, young men with pharmacokinetic and pharmacodynamic consequences."	( Modulation of metoprolol pharmacokinetics and hemodynamics by diphenhydramine coadministration during exercise testing in healthy premenopausal women. Arsenault, M; Bélanger, PM; Dumesnil, JG; Hamelin, BA; Meibohm, B; Pibarot, P; Pilote, S; Sharma, A, 2005)	0.9
" The objective of this study was to investigate differences in the pharmacokinetic patterns between a pulsatile drug delivery system using a pulsatile capsule, an immediate release tablet and a controlled release tablet."	( Pharmacokinetics of an immediate release, a controlled release and a two pulse dosage form in dogs. Amidon, GL; Kim, JS; Löbenberg, R, 2005)	0.33
"Human pharmacokinetic parameters are often predicted prior to clinical study from in vivo preclinical pharmacokinetic data."	( Extrapolation of human pharmacokinetic parameters from rat, dog, and monkey data: Molecular properties associated with extrapolative success or failure. Jolivette, LJ; Ward, KW, 2005)	0.33
" Based on these findings, three clinical studies were carried out to investigate pharmacokinetic drug interactions in vivo with gefitinib."	( Pharmacokinetic drug interactions of gefitinib with rifampicin, itraconazole and metoprolol. Laight, A; Leadbetter, J; McKillop, D; Ranson, M; Smith, RP; Swaisland, HC; Wild, MJ, 2005)	0.55
" In vitro kinetics and in vivo pharmacokinetic profiles after oral administration of timolol, metoprolol, and propranolol, were investigated in rats using the depletion assay."	( Application of substrate depletion assay for early prediction of nonlinear pharmacokinetics in drug discovery: assessment of nonlinearity of metoprolol, timolol, and propranolol. Iwaki, M; Kawase, A; Komura, H, 2005)	0.75
"The present work addressed possible alterations in the pharmacokinetics and the in vivo pharmacodynamic of metoprolol (MET) in spontaneously hypertensive (SH) rats and Wistar Kyoto (WKY) animals by means of the microdialysis technique."	( Pharmacokinetic-pharmacodynamic (PK-PD) modeling of cardiovascular effects of metoprolol in spontaneously hypertensive rats: a microdialysis study. Bramuglia, GF; Di Verniero, C; Höcht, C; Opezzo, JA; Taira, CA, 2006)	0.78
" The simulation-estimation study suggests that a greater separation between two subpopulations, a smaller variability in the parameter distribution, a larger sample size, and a smaller size subpopulation tend to be associated with a greater accuracy of subpopulation classification when a mixture model is applied to pharmacokinetic data."	( Mixture models and subpopulation classification: a pharmacokinetic simulation study and application to metoprolol CYP2D6 phenotype. Brundage, RC; Kaila, N; Straka, RJ, 2007)	0.55
" In summary, the present study provides the first evidence of a change in the in vitro pharmacodynamic properties of metoprolol in SHR."	( Changes in the in vitro pharmacodynamic properties of metoprolol in atria isolated from spontaneously hypertensive rats. Di Verniero, C; Höcht, C; Opezzo, JA; Taira, CA, 2007)	0.8
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."	( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds. Lombardo, F; Obach, RS; Waters, NJ, 2008)	0.35
"This study of metoprolol pharmacokinetic and pharmacodynamic properties investigates cardiac beta1-adrenoceptors activity and its involvement in the hypertensive stage in 6-week-old fructose-fed male Sprague-Dawley rats."	( In vitro and in vivo pharmacodynamic properties of metoprolol in fructose-fed hypertensive rats. Di Verniero, CA; Höcht, C; Mayer, MA; Opezzo, JA; Silberman, EA; Taira, CA, 2008)	0.96
" The pharmacokinetic parameters of metoprolol and its metabolite, alpha-hydroxymetoprolol, and the metabolic ratio for the three groups were estimated and compared."	( Influence of CYP2D6*10 on the pharmacokinetics of metoprolol in healthy Korean volunteers. Bang, S; Chung, HJ; Chung, MW; Jin, SK; Kang, JH; Kim, JI; Lee, HJ; Lee, SH; Roh, J; Woo, SW, 2008)	0.88
" Comparative pharmacokinetic-pharmacodynamic studies with four beta blockers were performed in conscious rats, using heart rate under isoprenaline-induced tachycardia as a pharmacodynamic endpoint."	( Influence of plasma protein binding on pharmacodynamics: Estimation of in vivo receptor affinities of beta blockers using a new mechanism-based PK-PD modelling approach. Boralli, VB; Danhof, M; de Lange, EC; Freijer, J; Krekels, EH; Slijkerman, P; van Steeg, TJ, 2009)	0.35
" The pharmacokinetic parameters of MET and META were measured after oral (15 mg/kg) administration of MET in rats in the presence and absence of SalB."	( The effects of salvianolic acid B from radix salvia miltiorrhizae on the oral pharmacokinetics of metoprolol and metoprolol acid in rats. Liu, CX; Wan, RZ; Zhou, MJ, 2010)	0.58
" These results demonstrate a pharmacokinetic interaction between paroxetine and both formulations of metoprolol."	( Influence of metoprolol dosage release formulation on the pharmacokinetic drug interaction with paroxetine. Bleske, BE; Brook, R; Kerber, K; Nielsen, J; Shea, M; Stout, SM; Welage, LS, 2011)	0.95
" The pharmacokinetic parameters were estimated using previously developed barrier-limited and space-distributed models."	( Liver fibrosis impairs hepatic pharmacokinetics of liver transplant drugs in the rat model. Asadian, P; Crawford, DH; Fletcher, LM; Khlentzos, AM; Li, P; Liu, X; Roberts, MS; Robertson, TA; Thorling, CA; Zou, YH, 2010)	0.36
" Studies were undertaken using an in situ-perfused rat liver and multiple indicator dilution, and outflow data were analyzed with a physiologically based organ pharmacokinetic model."	( Hepatic pharmacokinetics of cationic drugs in a high-fat emulsion-induced rat model of nonalcoholic steatohepatitis. Crawford, DH; Fletcher, LM; Li, P; Roberts, MS; Robertson, TA; Thorling, CA; Zhang, Q, 2011)	0.37
"In vitro anti-resorptive activity, mechanism of action, pharmacokinetic profile and in vivo anti-resorptive activity of N(1),N(1)-diisopropyl-N(2)-(diphenylphosphoryl)-2-(4-nitrophenyl)acetamidine (1) were evaluated."	( Anti-resorptive activity and pharmacokinetic study of N(1),N(1)-diisopropyl-N(2)-(diphenylphosphoryl)-2-(4-nitrophenyl)acetamidine. Kim, MH; Kim, SH; Park, M; Park, SJ; Song, JS, 2011)	0.37
"After receiving metoprolol on days 1 (before paroxetine) and 8 (after paroxetine), S- and R-metoprolol pharmacokinetic parameters and exercise heart rate and blood pressure responses were measured."	( Effects of paroxetine on the pharmacokinetics and pharmacodynamics of immediate-release and extended-release metoprolol. Parker, RB; Soberman, JE, 2011)	0.93
" Hepatic pharmacokinetic modelling was performed with a two-phase physiologically-based organ pharmacokinetic model with the vascular space and dispersion evaluated with the MID technique."	( Hepatocellular necrosis, fibrosis and microsomal activity determine the hepatic pharmacokinetics of basic drugs in right-heart-failure-induced liver damage. Crawford, DH; Fletcher, LM; Li, P; Roberts, MS; Robertson, TA; Weiss, M; Zhang, Q, 2012)	0.38
" Hepatic pharmacokinetic analysis showed that both the CL int and PS were significantly decreased in the RHF rat livers."	( Hepatocellular necrosis, fibrosis and microsomal activity determine the hepatic pharmacokinetics of basic drugs in right-heart-failure-induced liver damage. Crawford, DH; Fletcher, LM; Li, P; Roberts, MS; Robertson, TA; Weiss, M; Zhang, Q, 2012)	0.38
" Thus, the pharmacokinetic interaction between metoprolol (anti-hypertension drug) and SP-8203 (a new drug candidate for cerebral ischemia) with respect to the metabolism via CYP isozymes was evaluated."	( Pharmacokinetic interaction between metoprolol and SP-8203 in rats: competitive inhibition for the metabolism of metoprolol by SP-8203 via hepatic CYP2D subfamily. Chin, YW; Cho, IW; Choi, YH; Han, SY; Lee, MG; Yoon, I, 2012)	0.91
" We have used a pregnancy physiologically based pharmacokinetic (p-PBPK) model to assess the likely impact of pregnancy on three model compounds, namely caffeine, metoprolol and midazolam, based on the knowledge of their disposition in nonpregnant women and information from in vitro studies."	( A pregnancy physiologically based pharmacokinetic (p-PBPK) model for disposition of drugs metabolized by CYP1A2, CYP2D6 and CYP3A4. Abduljalil, K; Gaohua, L; Jamei, M; Johnson, TN; Rostami-Hodjegan, A, 2012)	0.57
" Plasma samples obtained, up to 24 hr after dosing, from four male and four female Microminipigs were analyzed by liquid chromatography tandem mass spectrometry to estimate typical pharmacokinetic parameters for each analyte."	( Simultaneous pharmacokinetics assessment of caffeine, warfarin, omeprazole, metoprolol, and midazolam intravenously or orally administered to Microminipigs. Iwasaki, K; Izumi, H; Kusumoto, S; Mogi, M; Murayama, N; Shimizu, M; Takehara, H; Toda, A; Utoh, M; Yamazaki, H, 2012)	0.61
" The validated assay was applied to a pharmacokinetic study in rats."	( Validated LC-ESI-MS/MS method for simultaneous quantitation of felodipine and metoprolol in rat plasma: application to a pharmacokinetic study in rats. Kallem, RR; Ramesh, M; Seshagirirao, JV, 2013)	0.62
"To develop a pharmacokinetic model able to describe the nonlinear pharmacokinetics of paroxetine (PRX) and to predict the drug-drug interaction between PRX and metoprolol under various dosage regimens."	( Pharmacokinetic model incorporating mechanism-based inactivation of CYP2D6 can explain both non-linear kinetics and drug interactions of paroxetine. Hori, S; Mikami, A; Ohtani, H; Sawada, Y, 2013)	0.59
"A pharmacokinetic model of PRX incorporating mechanism-based inhibition was developed."	( Pharmacokinetic model incorporating mechanism-based inactivation of CYP2D6 can explain both non-linear kinetics and drug interactions of paroxetine. Hori, S; Mikami, A; Ohtani, H; Sawada, Y, 2013)	0.39
" To increase robustness of metoprolol pharmacokinetic estimates, a systematic review and meta-analysis of pharmacokinetic studies that administered a single oral dose of immediate-release metoprolol were performed."	( A meta-analysis of CYP2D6 metabolizer phenotype and metoprolol pharmacokinetics. Blake, CM; Kharasch, ED; Nagele, P; Schwab, M, 2013)	0.94
" Pharmacokinetic and pharmacodynamic changes depend on the nature and degree of hepatic impairment and on the characteristics of the dosed drug."	( [Effect of liver cirrhosis on pharmacokinetics and pharmacodynamics of drugs]. Perlík, F, 2013)	0.39
" In this study, we evaluated pharmacokinetic changes following intravenous (i."	( Faster non-renal clearance of metoprolol in streptozotocin-induced diabetes mellitus rats. Kang, HE; Lee, BK; Lee, I; Lee, U, 2013)	0.68
" Maximum observed plasma concentration (Cmax) of metoprolol in treatment B significantly decreased, whereas Cmax in treatment C was slightly decreased."	( The effect of AST-120 on the single-dose pharmacokinetics of metoprolol extended-release tablets in healthy subjects. Akimoto, K; Arita, K; Inoue, S; Shimizu, M, 2014)	0.9
" The noncompartmental pharmacokinetic parameters were computed for metoprolol, its metabolite alpha-hydroxymetoprolol, and pyronaridine."	( Pharmacokinetic interaction between pyronaridine-artesunate and metoprolol. Arbe-Barnes, S; Borghini-Fuhrer, I; Duparc, S; Fleckenstein, L; Lopez-Lazaro, L; Miller, RM; Morris, CA; Pokorny, R; Shin, JS, 2014)	0.88
" Changes in heart rate and blood pressure were monitored as pharmacodynamic responses to metoprolol."	( Effect of the potent CYP2D6 inhibitor sarpogrelate on the pharmacokinetics and pharmacodynamics of metoprolol in healthy male Korean volunteers. Bae, SH; Bae, SK; Cho, DY; Kim, BT; Kim, YW; Lee, JK; Lee, S; Oh, E; Park, JB, 2015)	0.86
" Well-controlled GDM prolonged tmax for both enantiomers of metoprolol (1."	( Influence of gestational diabetes on the stereoselective pharmacokinetics and placental distribution of metoprolol and its metabolites in parturients. Antunes, Nde J; Cavalli, RC; Lanchote, VL; Marques, MP; Moisés, EC, 2015)	0.87
" Well-controlled GDM prolonged the tmax of metoprolol and O-desmethylmetoproloic acid enantiomers and the α-hydroxymetoprolol stereoisomers and reduced by about 20% the transplacental distribution of 1'S,2S-, 1'R,2R-, and 1'R,2S-OHM."	( Influence of gestational diabetes on the stereoselective pharmacokinetics and placental distribution of metoprolol and its metabolites in parturients. Antunes, Nde J; Cavalli, RC; Lanchote, VL; Marques, MP; Moisés, EC, 2015)	0.89
" Compared with the rats exposed to normal altitude, the rats with acute exposure to high altitude showed significant alterations in the pharmacokinetic parameters of the drugs, shown by increased Cmax and AUC, prolonged t1/2 and MRT, and lowered Clz/F of propranolol, and by increased Tmax and prolonged t1/2 and MRT of metoprolol without obvious changes of the parameters of the compartmental model."	( [Effect of acute exposure to high altitude on pharmacokinetics of propranolol and metoprolol in rats]. Jia, Z; Li, W; Wang, R; Xie, H; Yin, Q; Zhang, J, 2014)	0.8
"Volume of distribution is one of the most important pharmacokinetic properties of a drug candidate."	( Volume of Distribution in Drug Design. Beaumont, K; Di, L; Maurer, TS; Smith, DA, 2015)	0.42
"The pharmacokinetics of cytochrome P450 probes in humans can be extrapolated from corresponding data in cynomolgus monkeys using simplified physiologically based pharmacokinetic (PBPK) modeling."	( Human plasma concentrations of five cytochrome P450 probes extrapolated from pharmacokinetics in dogs and minipigs using physiologically based pharmacokinetic modeling. Shida, S; Yamazaki, H, 2016)	0.43
"Our data show a potential pharmacokinetic interaction, most likely via CYP3A4 between amlodipine and RIS, reflected in significantly different C/Ds for RIS, 9-OH-RIS and AM."	( Pharmacokinetic considerations in the treatment of hypertension in risperidone-medicated patients - thinking of clinically relevant CYP2D6 interactions. Gründer, G; Haen, E; Lammertz, SE; Paulzen, M; Schoretsanitis, G; Schruers, KR; Stegmann, B; Walther, S, 2016)	0.43
"The use of in vitro-in vivo extrapolation (IVIVE) techniques, mechanistically incorporated within physiologically based pharmacokinetic (PBPK) models, can harness in vitro drug data and enhance understanding of in vivo pharmacokinetics."	( The Constraints, Construction, and Verification of a Strain-Specific Physiologically Based Pharmacokinetic Rat Model. Harwood, MD; Jamei, M; Musther, H; Rostami-Hodjegan, A; Turner, DB; Yang, J, 2017)	0.46
" The mean hepatic clearances determined by in silico fitting for individual pharmacokinetic models of warfarin and midazolam in the aged group were, respectively, 23% and 56% smaller than those for the young group."	( Effects of aging and rifampicin pretreatment on the pharmacokinetics of human cytochrome P450 probes caffeine, warfarin, omeprazole, metoprolol and midazolam in common marmosets genotyped for cytochrome P450 2C19. Inoue, T; Kusama, T; Mogi, M; Sasaki, E; Shimizu, M; Toda, A; Uehara, S; Uno, Y; Utoh, M; Yamazaki, H, 2018)	0.68
"Physiologically based pharmacokinetic modeling is considered a valuable tool for predicting pharmacokinetic changes in pregnancy to subsequently guide in-vivo pharmacokinetic trials in pregnant women."	( A Physiologically Based Pharmacokinetic Model for Pregnant Women to Predict the Pharmacokinetics of Drugs Metabolized Via Several Enzymatic Pathways. Coboeken, K; Dallmann, A; Eissing, T; Hempel, G; Ince, I, 2018)	0.48
"Quantitative information on gestation-specific changes in enzyme activity available in the literature was incorporated in a pregnancy physiologically based pharmacokinetic model and the pharmacokinetics of eight drugs metabolized via one or multiple cytochrome P450 enzymes was predicted."	( A Physiologically Based Pharmacokinetic Model for Pregnant Women to Predict the Pharmacokinetics of Drugs Metabolized Via Several Enzymatic Pathways. Coboeken, K; Dallmann, A; Eissing, T; Hempel, G; Ince, I, 2018)	0.48
"The pregnancy physiologically based pharmacokinetic model successfully predicted the pharmacokinetics of all tested drugs."	( A Physiologically Based Pharmacokinetic Model for Pregnant Women to Predict the Pharmacokinetics of Drugs Metabolized Via Several Enzymatic Pathways. Coboeken, K; Dallmann, A; Eissing, T; Hempel, G; Ince, I, 2018)	0.48
"The presented pregnancy physiologically based pharmacokinetic model can quantitatively predict the pharmacokinetics of drugs that are metabolized via one or multiple cytochrome P450 enzymes by integrating prior knowledge of the pregnancy-related effect on these enzymes."	( A Physiologically Based Pharmacokinetic Model for Pregnant Women to Predict the Pharmacokinetics of Drugs Metabolized Via Several Enzymatic Pathways. Coboeken, K; Dallmann, A; Eissing, T; Hempel, G; Ince, I, 2018)	0.48
" Physiologically based pharmacokinetic (PBPK) modeling was conducted using a population-based simulator."	( Physiologically Based Pharmacokinetic Modeling to Evaluate the Systemic Exposure of Gefitinib in CYP2D6 Ultrarapid Metabolizers and Extensive Metabolizers. Al-Huniti, N; Chen, Y; Masson, E; Tang, W; Zhou, D; Zhou, W, 2018)	0.48
" This study aims to evaluate the possible pharmacokinetic changes in NAFLD as a result of reduced metabolic activity of CYP2D."	( Effects of Orotic Acid-Induced Non-Alcoholic Fatty Liver on the Pharmacokinetics of Metoprolol and its Metabolites in Rats. Bang, WS; Hwang, YR; Kang, HE; Lee, I; Li, Z, 2019)	0.74
"Physiologically based pharmacokinetic (PBPK) modelling and simulation is a useful tool in predicting the PK profiles of a drug, assessing the effects of covariates such as demographics, ethnicity, genetic polymorphisms and disease status on the PK, and evaluating the potential of drug-drug interactions."	( Development of a Korean-specific virtual population for physiologically based pharmacokinetic modelling and simulation. Chung, JY; Hatley, O; Kim, Y; Lee, H; Lee, HA; Rhee, SJ; Yi, S; Yoon, S; Yu, KS, 2019)	0.51
" In this study we developed and qualified a physiologically based pharmacokinetic model to systematically investigate the influence of drug- and formulation-related properties on the oral absorption and bioequivalence of modified-release products using metoprolol as an example."	( Physiologically Based Pharmacokinetic Modeling to Evaluate Formulation Factors Influencing Bioequivalence of Metoprolol Extended-Release Products. Basu, S; Fang, L; Gonzalez-Sales, M; Lesko, L; Schmidt, S; Trame, MN; Yang, H; Zhao, L, 2019)	0.91
"Recent CYP2D6 phenotype standardization efforts by CYP2D6 activity score (AS) are based on limited pharmacokinetic (PK) and pharmacodynamic (PD) data."	( Examination of Metoprolol Pharmacokinetics and Pharmacodynamics Across CYP2D6 Genotype-Derived Activity Scores. Binkley, PF; Cavallari, LH; Chapman, AB; Cooper-DeHoff, RM; El Rouby, N; Estores, DS; Fang, L; Feng, K; Frye, RF; Gong, Y; Gums, JG; Hamadeh, IS; Johnson, JA; Kim, H; Kim, S; Kinjo, M; Langaee, TY; Li, Z; Lingineni, K; Mosley, SA; Schmidt, S; Schmidt, SO; Thomas, CD; Wang, D; Zhao, L, 2020)	0.91
"The plasma concentrations of metoprolol were determined using Reverse Phase-High Performance Liquid Chromatography (RP-HPLC) on the 1st day in single-dose pharmacokinetic (PK) study (SDS) and on the 15th day in multiple dosing PK studies (MDS)."	( Effect of naringenin on the pharmacokinetics of metoprolol succinate in rats. Dirisala, VR; Gullapalli, Y; Kilaru, NB; Mullapudi, SS; Pingili, RB; Vemulapalli, S, 2021)	1.17
" A physiologically based pharmacokinetic model for tramadol and O-desmethyltramadol was developed and verified in PK-Sim version 8 and linked to respective models of quinidine and metoprolol to evaluate the impact of allosteric and competitive CYP2D6 inhibition on tramadol and O-desmethyltramadol exposure."	( Physiologically Based Pharmacokinetic Modeling to Assess the Impact of CYP2D6-Mediated Drug-Drug Interactions on Tramadol and O-Desmethyltramadol Exposures via Allosteric and Competitive Inhibition. Cicali, B; Cristofoletti, R; Dow, P; Long, T; Michaud, V; Schmidt, S; Turgeon, J, 2022)	0.91
" Although some studies have explored the roles of gut microbiota and host Cyp450s in drug pharmacokinetics, few have explored their effects on pharmacokinetic variability, especially in disease states."	( Gut microbiota and host Cyp450s co-contribute to pharmacokinetic variability in mice with non-alcoholic steatohepatitis: Effects vary from drug to drug. Chen, LJ; Chen, XP; Chen, Y; Guo, J; Liou, YL; Tan, ZR; Xu, Y; Zhang, SX; Zhang, W; Zhou, HH, 2022)	0.72
"In this study, we aim to investigate the effects of gut microbiota and host Cyp450s on pharmacokinetic variability in mice with non-alcoholic steatohepatitis (NASH), and to elucidate the contribution of gut microbiota and host Cyp450s to pharmacokinetic variability in this setting."	( Gut microbiota and host Cyp450s co-contribute to pharmacokinetic variability in mice with non-alcoholic steatohepatitis: Effects vary from drug to drug. Chen, LJ; Chen, XP; Chen, Y; Guo, J; Liou, YL; Tan, ZR; Xu, Y; Zhang, SX; Zhang, W; Zhou, HH, 2022)	0.72
"The pharmacokinetic variability of mice with NASH was explored under intragastric and intravenous administrations of a cocktail mixture of omeprazole, phenacetin, midazolam, tolbutamide, chlorzoxazone, and metoprolol, after which the results were compared with those obtained from the control group."	( Gut microbiota and host Cyp450s co-contribute to pharmacokinetic variability in mice with non-alcoholic steatohepatitis: Effects vary from drug to drug. Chen, LJ; Chen, XP; Chen, Y; Guo, J; Liou, YL; Tan, ZR; Xu, Y; Zhang, SX; Zhang, W; Zhou, HH, 2022)	0.91
" The pharmacokinetic variabilities of phenacetin, midazolam, omeprazole, and chlorzoxazone were mainly associated with decreased elimination activity in the gut microbiota."	( Gut microbiota and host Cyp450s co-contribute to pharmacokinetic variability in mice with non-alcoholic steatohepatitis: Effects vary from drug to drug. Chen, LJ; Chen, XP; Chen, Y; Guo, J; Liou, YL; Tan, ZR; Xu, Y; Zhang, SX; Zhang, W; Zhou, HH, 2022)	0.72
"Gut microbiota and host Cyp450s co-contribute to the pharmacokinetic variability in mice with NASH, and the degree of contribution varies from drug to drug."	( Gut microbiota and host Cyp450s co-contribute to pharmacokinetic variability in mice with non-alcoholic steatohepatitis: Effects vary from drug to drug. Chen, LJ; Chen, XP; Chen, Y; Guo, J; Liou, YL; Tan, ZR; Xu, Y; Zhang, SX; Zhang, W; Zhou, HH, 2022)	0.72
" This study aimed to build a physiologically based pharmacokinetic (PBPK) model reflecting observed changes in physiological and molecular parameters relevant to drug disposition that are associated with MAFLD."	( A Physiologically Based Pharmacokinetic Model to Predict the Impact of Metabolic Changes Associated with Metabolic Associated Fatty Liver Disease on Drug Exposure. Newman, EM; Rowland, A, 2022)	0.72

Excerpt	Reference	Relevance
" Metoprolol in combination with chlorathalidone appears to be an effective and well-tolerated treatment for mild and moderate hypertension in patients not responding to chlorthalidone alone."	( A controlled study on the anti-hypertensive effect of a new beta-adrenoreceptor-blocking drug, metoprolol, in combination with chlorthalidone. Jäättelä, A; Pyörälä, K, 1976)	1.38
" Altogether, 251 hypertensive patients with a diastolic blood pressure greater than 95 mm Hg after 4 weeks of treatment with placebo in combination with metoprolol CR 100 mg were randomized to four parallel groups."	( Optimal felodipine dose when combined with metoprolol in arterial hypertension: a Swedish multicenter study within primary health care. Swedish General Practitioner Felodipine Study Group. Bengtsson, C; Brun, J; Fröberg, L; Kronmann, P; Olsson, LB; Scherstén, B; Skoog, P; Tibblin, G; Tygesen, G, 1990)	0.74
" Inosine in combination with ADA antagonized the noradrenaline-induced positive inotropic effect and the increase in cardiac output."	( Hemodynamic effects of inosine in combination with positive and negative inotropic drugs: studies on rats in vivo. Seesko, RC; Zimmer, HG, 1990)	0.28
"9% NaCl solution; vehicle) was given, alone and in combination with lidocaine (L), to groups of six pentobarbital (32."	( Effects of metoprolol, alone and in combination with lidocaine, on ventricular fibrillation threshold: comparison with atenolol, propranolol, and pindolol. Beil, ME; Cabot, CF; Coram, WM; Olson, RW; Weiss, GB, 1987)	0.66
" We therefore studied its functional and metabolic effects in closed chest rats when given in combination with prazosin, verapamil or metoprolol, all of which have direct effects on the circulation."	( Functional and metabolic effects of ribose in combination with prazosin, verapamil and metoprolol in rats in vivo. Lortet, S; Zimmer, HG, 1989)	0.7
"In a double-blind trial, 545 out-patients with essential hypertension received 25 mg/day chlorthalidone alone (274 patients) or in fixed combination with 200 mg/day slow-release metoprolol (271 patients) for 8 weeks."	( Chlorthalidone alone or in fixed combination with slow-release metoprolol in the management of arterial hypertension: a long-term study of 545 patients. Alberti, D; Bichisao, E; Gambini, O; Merlini, L; Pollavini, G, )	0.56
"The study was a comparison of the effects on respiratory function produced by four antihypertensive agents with receptor-blocking properties (atenolol, oxprenolol, labetalol, metoprolol), when used in combination with a diuretic (chlorthalidone) in four homogeneous groups of hypertensive patients also suffering from chronic obstructive lung disease."	( Respiratory effects of four adrenergic blocking agents combined with a diuretic in treating hypertension with concurrent chronic obstructive lung disease. Dal Negro, RW; Pomari, C; Trevisan, F; Turco, P; Zoccatelli, O, 1986)	0.46
"The long-term safety and efficacy of ketanserin in the treatment of essential hypertension was assessed in monotherapy or in combination with the beta-blocker, metoprolol."	( Long-term safety and efficacy of ketanserin in essential hypertension: ketanserin versus or in combination with metoprolol. Mauersberger, H, 1986)	0.68
" 3 In four patients being treated with the drug combination first and thereafter with propafenone alone no changes in the steady-state levels of propafenone were observed between both treatment periods."	( Drug interaction between propafenone and metoprolol. Jähnchen, E; Kalusche, D; Roskamm, H; Trenk, D; Wagner, F, 1987)	0.54
"The widely used acetylsalicylic acid (ASA, Colfarit) was administered in combination with metoprolol (Lopresor) during 7 days."	( Pharmacokinetics of salicylates administered with metoprolol. Kirch, W; Langguth, P; Mutschler, E; Ohnhaus, EE; Spahn, H, 1986)	0.75
" 17 patients (group I) got fenoterol-monotherapy; in 18 patients (group II) fenoterol was combined with the cardioselective beta-1-blocking agent metoprolol."	( [Efficency of tocoylsis by fenoterol and fenoterol in combination with a beta-1-blocking compound (author's transl)]. Bernius, U; Hillemanns, HG; Irmer, M; Pohl, C; Steim, H; Trolp, R, 1980)	0.46
"The hemodynamic and myocardial metabolic effects of enoximone (phosphodiesterase III inhibitor), alone or in combination with metoprolol (beta-adrenergic blocker), were studied in patients with congestive heart failure."	( Effect of enoximone alone and in combination with metoprolol on myocardial function and energetics in severe congestive heart failure: improvement in hemodynamic and metabolic profile. Branzi, A; Caldarera, I; Galie, N; Grattoni, C; Magnani, B; Magnani, G; Melandri, G; Rapezzi, C, 1993)	0.75
"This prospective, randomized study assessed the safety and efficacy of metoprolol alone or combined with amlodipine on hemodynamic parameters at baseline, 2 hours after the first dose of study medication, and after 12 weeks of therapy in patients receiving background triple therapy for mild to severe heart failure."	( Short-term and long-term hemodynamic and clinical effects of metoprolol alone and combined with amlodipine in patients with chronic heart failure. Buchholz-Varley, C; Freudenberger, RS; Kalman, J; Kukin, ML; Mannino, MM; Ocampo, ON; Steinmetz, M, 1999)	0.78
" The autopsy and the consecutive chemical-toxicological investigation revealed that the deceased committed suicide by injecting an overdose of insulin in combination with a high therapeutic oral bolus application of a beta-blocker (Metoprolol)."	( Suicide by insulin injection in combination with beta-blocker application. Junge, M; Püschel, K; Tsokos, M, 2000)	0.49
"Treatment with growth hormone alone or in combination with metoprolol preserved left ventricular function after MI."	( Growth hormone alone or combined with metoprolol preserves cardiac function after myocardial infarction in rats. Bengtsson, BA; Bergh, CH; Bollano, E; Caidahl, K; Isgaard, J; Kjellström, C; Kujacic, V; Omerovic, E; Waagstein, F, 2001)	0.83
" We report the use of a short-acting intravenous beta blocker in combination with inotropic therapy as a means to bridge five patients with advanced heart failure to chronic oral beta blockade; two of these patients had been chronically managed with intravenous inotrope."	( Novel use of a short-acting intravenous beta blocker in combination with inotropic therapy as a bridge to chronic oral beta blockade in patients with advanced heart failure. Hauptman, PJ; Prirzker, MR; Woods, D, 2002)	0.31
" However, this component may take part in vivo and contribute to drug-drug interactions involving P-gp."	( pH-dependent bidirectional transport of weakly basic drugs across Caco-2 monolayers: implications for drug-drug interactions. Artursson, P; Neuhoff, S; Ungell, AL; Zamora, I, 2003)	0.32
" In this study, we aimed to assess the effect of low-dose cardio-selective beta blocker combination with sibutramine treatment."	( Effect of low-dose metoprolol in combination with sibutramine therapy in normotensive obese patients: a randomized controlled study. Baykan, M; Durmus, I; Erem, C; Ersoz, HO; Hacihasanoglu, A; Telatar, M; Ukinc, K, 2004)	0.65
"To compare efficacy and safety of nifedipin-retard (cordaflex-retard, Egis, Hungary) used in monotherapy and in combination with metoprolol (egilok, Egis, Hungary) in patients with arterial hypertension (AH)."	( [Assessment of the efficacy and tolerance of delayed-action nifedipine as the monotherapy or in combination with metoprolol in patients with arterial hypertension]. Andreeva, GF; Dmitrieva, NA; Gorbunov, VM; Isaĭkina, OIu; Martsevich, SIu, 2003)	0.73
" Nifedipin-retard was given in a daily dose 40 mg/day (20 mg twice a day) in monotherapy and 20 mg/day in combination with metoprolol which was administered 50 mg twice a day (a daily dose 100 mg/day)."	( [Assessment of the efficacy and tolerance of delayed-action nifedipine as the monotherapy or in combination with metoprolol in patients with arterial hypertension]. Andreeva, GF; Dmitrieva, NA; Gorbunov, VM; Isaĭkina, OIu; Martsevich, SIu, 2003)	0.74
" Side effects observed in nifedipin-retard monotherapy got much more weaker when this drug combined with metoprolol."	( [Assessment of the efficacy and tolerance of delayed-action nifedipine as the monotherapy or in combination with metoprolol in patients with arterial hypertension]. Andreeva, GF; Dmitrieva, NA; Gorbunov, VM; Isaĭkina, OIu; Martsevich, SIu, 2003)	0.74
" However it has important drug-drug interactions related to the cytochrome P450 system."	( Severe sinus bradycardia after initiation of bupropion therapy: a probable drug-drug interaction with metoprolol. Greene, JL; McCollum, DL; McGuire, DK, 2004)	0.54
"The purpose of this study was to propose a new method to predict in vivo drug-drug interactions (DDIs) for a high clearance drug from in vitro data."	( Prediction of drug-drug interactions for AUCoral of high clearance drug from in vitro data: utilization of a microtiter plate assay and a dispersion model. Kohno, Y; Nagata, K; Suzuki, A; Yamamoto, T; Yamazoe, Y, 2006)	0.33
" This study examined the effects of treatment with Ran alone and in combination with metoprolol (Met) or enalapril (Ena) on LV function and remodeling in dogs with HF."	( Ranolazine combined with enalapril or metoprolol prevents progressive LV dysfunction and remodeling in dogs with moderate heart failure. Belardinelli, L; Blackburn, B; Gupta, RC; Mishra, S; Rastogi, S; Sabbah, HN; Sharov, VG; Stanley, WC, 2008)	0.84
" The CYP2D6 inhibitor paroxetine has previously been shown to interact with metoprolol tartrate."	( Influence of metoprolol dosage release formulation on the pharmacokinetic drug interaction with paroxetine. Bleske, BE; Brook, R; Kerber, K; Nielsen, J; Shea, M; Stout, SM; Welage, LS, 2011)	0.97
" Metoprolol in combination with chlorthalidone appears to be an effective and well-tolerated treatment for mild and moderate hypertension in those patients not responding to chlorthalidone alone."	( A controlled study on the antihypertensive effect of a new beta-adrenergic receptor blocking drug, metoprolol, in combination with chlorthalidone. Jäättelä, A; Pyörälä, K, 1976)	1.38
"The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug-drug interactions."	( Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. Artursson, P; Haglund, U; Karlgren, M; Kimoto, E; Lai, Y; Norinder, U; Vildhede, A; Wisniewski, JR, 2012)	0.38
"To develop a pharmacokinetic model able to describe the nonlinear pharmacokinetics of paroxetine (PRX) and to predict the drug-drug interaction between PRX and metoprolol under various dosage regimens."	( Pharmacokinetic model incorporating mechanism-based inactivation of CYP2D6 can explain both non-linear kinetics and drug interactions of paroxetine. Hori, S; Mikami, A; Ohtani, H; Sawada, Y, 2013)	0.59
"The developed model enabled us to quantitatively estimate drug-drug interactions of PRX and CYP2D6 substrate drugs, and to predict optimal dosage regimens."	( Pharmacokinetic model incorporating mechanism-based inactivation of CYP2D6 can explain both non-linear kinetics and drug interactions of paroxetine. Hori, S; Mikami, A; Ohtani, H; Sawada, Y, 2013)	0.39
"To investigate the effects of ivabradine in combination with perindopril on cerebral blood flow and endothelial functional activity."	( [Cerebral blood flow and endothelial functional activity in patients with coronary heart disease and arterial hypertension during therapy with ivabradine in combination with perindopril]. Gapon, LI; Kolesnikova, SN; Musikhina, NA; Petelina, TI; Utesheva, AB, 2012)	0.38
" Group 1 (n = 38) patients took ivabradine in combination with perindopril and Group 2 (n = 26) received metoprolol."	( [Cerebral blood flow and endothelial functional activity in patients with coronary heart disease and arterial hypertension during therapy with ivabradine in combination with perindopril]. Gapon, LI; Kolesnikova, SN; Musikhina, NA; Petelina, TI; Utesheva, AB, 2012)	0.59
"By unidirectionally affecting the vasomotor function of the endothelium, ivabradine in combination with perindopril versus metoprolol has a more favorable effect on circulatory resistance and blood flow velocity in the brachiocephalic arteries of patients with CHD and AH."	( [Cerebral blood flow and endothelial functional activity in patients with coronary heart disease and arterial hypertension during therapy with ivabradine in combination with perindopril]. Gapon, LI; Kolesnikova, SN; Musikhina, NA; Petelina, TI; Utesheva, AB, 2012)	0.59
" The results suggested that breviscapine have negligible effect on pharmacokinetics of MET in rats; the information may be beneficial for the application of breviscapine in combination with MET in clinical therapy."	( Development of a LC-MS/MS method for simultaneous determination of metoprolol and its metabolites, α-hydroxymetoprolol and O-desmethylmetoprolol, in rat plasma: application to the herb-drug interaction study of metoprolol and breviscapine. Ma, YR; Qin, HY; Rao, Z; Wang, XD; Wang, YF; Wei, YH; Wu, XA; Zhang, GQ; Zhou, Y, 2015)	0.65
"The ability of a chronic treatment with indacaterol, a new ultra-long-acting β2 -adrenoceptor agonist, to reverse cardiac remodelling and its effects in combination with metoprolol, a selective β1 -adrenoceptor antagonist, were investigated on myocardial infarction in a rat model of heart failure (HF)."	( Effects of chronic treatment with the new ultra-long-acting β2 -adrenoceptor agonist indacaterol alone or in combination with the β1 -adrenoceptor blocker metoprolol on cardiac remodelling. Calzetta, L; Capuano, A; Donniacuo, M; Gritti, G; Martuscelli, E; Matera, MG; Orlandi, A; Rafaniello, C; Rinaldi, B; Rossi, F; Sodano, L, 2015)	0.81
"ADDITIONS (prActical Daily efficacy anD safety of Procoralan® In combinaTION with betablockerS) was a multicenter, 4-month, noninterventional, prospective, open-label trial that involved stable-angina patients."	( Ivabradine in Combination with Metoprolol Improves Symptoms and Quality of Life in Patients with Stable Angina Pectoris: A post hoc Analysis from the ADDITIONS Trial. Ebelt, H; Höpfner, F; Müller-Werdan, U; Nuding, S; Stöckl, G; Werdan, K, 2016)	0.72
"Ivabradine combined with metoprolol safely and effectively reduces heart rate, angina attacks and nitrate use, and improves QoL in stable-angina patients."	( Ivabradine in Combination with Metoprolol Improves Symptoms and Quality of Life in Patients with Stable Angina Pectoris: A post hoc Analysis from the ADDITIONS Trial. Ebelt, H; Höpfner, F; Müller-Werdan, U; Nuding, S; Stöckl, G; Werdan, K, 2016)	1.02
"The aim of the present study was to evaluate the contribution of metabolites to drug-drug interaction and drug-herb interaction using the inhibition of CYP2D6 and CYP3A4 by metoprolol (MET) and its metabolites."	( An evaluation of the CYP2D6 and CYP3A4 inhibition potential of metoprolol metabolites and their contribution to drug-drug and drug-herb interaction by LC-ESI/MS/MS. Banerjee, SK; Bhandi, MM; Borkar, RM; Dubey, AP; Ganga Reddy, V; Kamal, A; Komirishetty, P; Nandekar, PP; Sangamwar, AT; Srinivas, R, 2016)	0.87
" The biosensor was optimized regarding the type of cantilever, temperature and exchange of media; in combination with standardized protocol, it allowed testing of compounds and conditions affecting the biomechanical properties of EB."	( Atomic force microscopy combined with human pluripotent stem cell derived cardiomyocytes for biomechanical sensing. Acimovic, I; Dvorak, P; Jelinkova, S; Lacampagne, A; Meli, AC; Pesl, M; Pribyl, J; Rotrekl, V; Salykin, A; Skladal, P; Vilotic, A, 2016)	0.43
" The new model is useful for estimating the risk of drug interaction in clinical practice when AST-120 is used in combination with other drugs."	( Prediction of drug interaction between oral adsorbent AST-120 and concomitant drugs based on the in vitro dissolution and in vivo absorption behavior of the drugs. Kotegawa, T; Koya, Y; Machi, Y; Namiki, N; Shobu, Y; Uchida, S, 2016)	0.43
" This leads to CYP2D6-mediated drug-drug interactions (DDI)."	( The burden and management of cytochrome P450 2D6 (CYP2D6)-mediated drug-drug interaction (DDI): co-medication of metoprolol and paroxetine or fluoxetine in the elderly. Bahar, MA; Borgsteede, SD; Bos, JHJ; Hak, E; Wilffert, B, 2017)	0.67
"Metoprolol (a CYP2D6 substrate) is often co-prescribed with paroxetine/fluoxetine (a CYP2D6 inhibitor) because the clinical relevance of this drug-drug interaction (DDI) is still unclear."	( The impact of CYP2D6 mediated drug-drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine. Bahar, MA; Borgsteede, SD; Hak, E; Kamp, J; Wilffert, B, 2018)	2.14
" As the management of drug-drug interactions (DDIs) constitutes a key aspect of the care of PLWH, the magnitude of pharmacokinetic DDIs between cardiovascular and anti-HIV drugs needs to be more thoroughly characterized."	( UHPLC-MS/MS assay for simultaneous determination of amlodipine, metoprolol, pravastatin, rosuvastatin, atorvastatin with its active metabolites in human plasma, for population-scale drug-drug interactions studies in people living with HIV. Alves Saldanha, S; Buclin, T; Cavassini, M; Courlet, P; Csajka, C; Decosterd, LA; Desfontaine, V; Marzolini, C; Spaggiari, D, 2019)	0.75
" Based on in vitro data, clinical trials were conducted to assess the potential for drug-drug interactions between eliglustat and digoxin (P-glycoprotein substrate), metoprolol (sensitive CYP2D6 substrate), a combined oral contraceptive (CYP3A substrate), and acid-reducing agents."	( Effect of eliglustat on the pharmacokinetics of digoxin, metoprolol, and oral contraceptives and absorption of eliglustat when coadministered with acid-reducing agents. Ibrahim, J; Peterschmitt, MJ; Puga, AC; Ross, L; Thibault, N; Turpault, S; Vu, L; Xue, Y, 2020)	1
"To investigate the effects of metoprolol succinate combined with Entresto (Sacubitril Valsartan Sodium Tablets) on cardiac function and coagulation function in patients with congestive heart failure (CHF)."	( Effects of Metoprolol Succinate Combined with Entresto on Cardiac Function Indexes and Coagulation Function in Patients with Congestive Heart Failure. Ding, Y; Li, J; Wei, Z; Zhu, L, 2022)	1.4
" The control group was cured with metoprolol succinate sustained-release tablets, and the study group was cured with metoprolol succinate sustained-release tablets combined with Entresto."	( Effects of Metoprolol Succinate Combined with Entresto on Cardiac Function Indexes and Coagulation Function in Patients with Congestive Heart Failure. Ding, Y; Li, J; Wei, Z; Zhu, L, 2022)	1.39
"Clinical practice demonstrated that LVESD and LVEDD decreased and LVEF increased after treatment with Entresto combined with metoprolol in CHF patients, which can effectively facilitate cardiac function and vascular endothelial function, reduce oxidative stress reaction, and improve blood coagulation indexes, suggesting that Entresto combined with metoprolol can improve ventricular remodeling with good safety."	( Effects of Metoprolol Succinate Combined with Entresto on Cardiac Function Indexes and Coagulation Function in Patients with Congestive Heart Failure. Ding, Y; Li, J; Wei, Z; Zhu, L, 2022)	1.32
"To find the effects of dapagliflozin in combination with metoprolol sustained-release tablets on cardiac function and prognosis in acute myocardial infarction patients after PCI."	( Effects of Dapagliflozin in Combination with Metoprolol Sustained-Release Tablets on Prognosis and Cardiac Function in Patients with Acute Myocardial Infarction after PCI. Liu, Z; Zhang, H, 2022)	1.23
" In order to explore the demand for cardiovascular disease treatment, make up for the lack of chronic diseases affecting people's physical harm, and improve the success rate of cardiovascular disease treatment, a method to observe the efficacy and myocardial remodeling of trimetazidine combined with metoprolol in elderly patients with coronary heart disease and heart failure based on integrated traditional Chinese and Western medicine was proposed."	( Observation of Curative Effect of Trimetazidine Combined with Metoprolol in Elderly Patients with Coronary Heart Disease Complicated with Heart Failure and the Effect of Myocardial Remodeling by Integrated Traditional Chinese and Western Medicine. Lu, Y; Ni, H; Shi, H; Sun, Y; Wang, F, 2022)	1.14
"In the present study, five simple, feasible, and sensitive Ultra-high-speed liquid chromatography combined with mass spectrometry detection methods, using electrospray ionization are proposed."	( Ultra-high-speed liquid chromatography combined with mass spectrometry detection analytical methods for the determination of nitrosamine drug substance-related impurities. Bessa-Jambrina, S; Galán-Rodríguez, C; López-García, R; Marlés-Torres, A, 2023)	0.91
"To observe the effect of amlodipine besylate combined with metoprolol in treating hypertension and heart failure."	( Improvement in hemodynamics of amlodipine besylate combined with metoprolol in patients with hypertension complicated by heart failure. Chen, C; Jiao, D; Shen, J; Zhang, W; Zhang, X; Zhu, G, 2023)	1.39
" They were divided into a control group (CG, metoprolol, n = 156) and an observation group (OG, moracizine combined with metoprolol, n = 160) based on the treatment they received."	( Effects of Moracizine Combined with Metoprolol on Hemodynamic Indices of the Left Atrium and Quality of Life in Patients with Atrial Fibrillation. Fu, T; Han, G; Zhang, Y, 2023)	1.44
"Moracizine combined with metoprolol is an effective treatment for AF patients."	( Effects of Moracizine Combined with Metoprolol on Hemodynamic Indices of the Left Atrium and Quality of Life in Patients with Atrial Fibrillation. Fu, T; Han, G; Zhang, Y, 2023)	1.49
"This research was designed to unveil the impacts of percutaneous coronary intervention via transradial artery access (TRA-PCI) combined with metoprolol on cardiac function and vascular endothelial function in elderly patients with coronary heart disease (CHD)."	( Effects of percutaneous coronary intervention via transradial artery access combined with metoprolol on cardiac function and vascular endothelial function in elderly patients with coronary heart disease. Cheng, F; Xu, J, 2023)	1.33

Excerpt	Reference	Relevance
" Metoprolol did not significantly influence the bioavailability or the time-course of HCT."	( Bioavailability and disposition of metoprolol and hydrochlorothiazide combined in one tablet and of separate doses of hydrochlorothiazide. Johnsson, G; Jordö, L; Lundborg, P; Persson, BA; Regärdh, CG; Rönn, O, 1979)	1.45
"The possible influence of food intake on the bioavailability of one nonselective and one cardioselective beta adrenoceptor antagonist, propranolol and metoprolol, was examined by serial determinations of the drug concentrations in blood of healthy subjects, taking single doses of the drugs both on an empty stomach and together with a standardized breakfast."	( Enhancement of the bioavailability of propranolol and metoprolol by food. Danielson, K; Melander, A; Scherstén, B; Wåhlin, E, 1977)	0.7
" These studies showed metoprolol CR/ZOK to have a similar beta 1-blocking activity to metoprolol CT but that the bioavailability of the new formulation was lower."	( The relationship between metoprolol plasma concentration and beta 1-blockade in healthy subjects: a study on conventional metoprolol and metoprolol CR/ZOK formulations. Abrahamsson, B; Bergstrand, R; Lücker, P; Olofsson, B; Regårdh, CG; Sandberg, A; Wieselgren, I, 1990)	0.9
" Considerations for a new drug preparation such as bioavailability and variability in relation to a standard treatment and the clinical significance of taking the drug with food and in increasing doses, are potential concerns that do not seem to be a problem for the therapeutic use of metoprolol CR/ZOK."	( Pharmacokinetic and biopharmaceutic aspects of once daily treatment with metoprolol CR/ZOK: a review article. Abrahamsson, B; Bergstrand, R; Regårdh, CG; Sandberg, A; Wieselgren, I, 1990)	0.69
" The bioavailability of the oral dose on day 1 and day 29 was 13% and 12."	( Acute and steady-state pharmacokinetics and antihypertensive effects of felodipine in patients with normal and impaired renal function. Aberg, J; Gelin, A; Karlberg, BE; Larsson, R; Regårdh, CG, 1990)	0.28
"The influence of food intake on the bioavailability of metoprolol from an OROS system has been investigated."	( Influence of food on the bioavailability of metoprolol from an OROS system; a study in healthy volunteers. Cohen, AF; de Boer, AG; Gubbens-Stibbe, JM; Schoemaker, HC; van den Berg, G; van Steveninck, F, 1990)	0.79
" The method has been applied to investigate the pharmacokinetics and bioavailability of metoprolol and also applied to clinical monitoring of metoprolol levels in patients."	( [Determination of metoprolol in plasma by gas chromatography and electron-capture detection]. Hu, YS; Tu, XD; Wang, GJ; Yang, XJ; Zheng, X, 1990)	0.84
" The oral bioavailability of metoprolol was lower (6-22%) during pregnancy than in non-pregnancy (9-49%)."	( The rhesus monkey as a model for studies of pregnancy induced changes in metoprolol metabolism. Högstedt, S; Lindberg, BS; Moström, U; Rane, A; Regårdh, CG, 1990)	0.8
" In all four studies the AUCs were significantly lower after metoprolol CR/ZOK compared to CT with the mean relative bioavailability being approximately similar (73-84%)."	( Pharmacokinetic and pharmacodynamic comparison of metoprolol CR/ZOK once daily with conventional tablets once daily and in divided doses. Bergstrand, R; Lücker, P; Moore, G; Olofsson, B; Wieselgren, I, 1990)	0.77
"In this steady state, cross-over study, the bioavailability and beta 1-blocking effects of metoprolol CR/ZOK 50 mg, conventional metoprolol 50 mg tablets and placebo were evaluated in 12 healthy male subjects (mean age 25 years) after once daily treatment in 5 days."	( Pharmacokinetic and pharmacodynamic evaluation of metoprolol controlled release (CR/ZOK) 50 mg in young subjects. Bergstrand, R; Lundborg, P; Olofsson, B; Sandberg, A; Wieselgren, I, 1990)	0.75
" The relative bioavailability of CR/ZOK to CT was 69."	( Pharmacokinetic and pharmacodynamic properties of controlled release (CR/ZOK) metoprolol in healthy Oriental subjects: a comparison with conventional formulations of metoprolol and atenolol. Darmansjah, I; Irawati, D; Moeloek, D; Muchtar, A; Setiawati, A; Siagian, M; Wong, E, 1990)	0.51
" administration of the beta blockers, no significant increase in area under the plasma drug concentration-time curve was observed for propranolol and metoprolol as a function of age, but for atenolol, a significant increase in area under the plasma drug concentration-time curve was seen in the 24-month-old rats, due to a decrease in renal function, as bioavailability of atenolol did not change in function of age."	( Effect of aging on the pharmcokinetics of atenolol, metoprolol and propranolol in the rat. Belpaire, FM; Bogaert, MG; Chauvelot-Moachon, L; de Smet, F; Rosseel, MT; Vermeulen, AM; Vynckier, LJ, 1990)	0.73
"Four double-blind, Latin-square studies were conducted to compare the pharmacokinetics and pharmacodynamic bioavailability of metoprolol OROS (oral osmotic) and the conventional tablet (CT) of metoprolol."	( Pharmacokinetic and pharmacodynamic comparison of an osmotic release oral metoprolol tablet and the metoprolol conventional tablet. Arnold, JD; Bouvet, AA; Castellana, J; Feliciano, NR; Leese, PT; Luders, RC; Redalieu, E; Schwartz, DJ; Shum, L; Zak, S, 1990)	0.72
" Betaxolol (Kerlon, 8) was found to exhibit an appropriate preclinical pharmacological and human pharmacokinetic profile (elevated oral bioavailability and prolonged plasma half-life) for the treatment of chronic cardiovascular diseases such as hypertension and angina."	( Synthesis of a series of compounds related to betaxolol, a new beta 1-adrenoceptor antagonist with a pharmacological and pharmacokinetic profile optimized for the treatment of chronic cardiovascular diseases. Binet, JL; Cavero, IG; Lefèvre-Borg, F; Manoury, PM; Rousseau, J, 1987)	0.27
" Although not affecting the pharmacodynamics of metoprolol, cimetidine did produce an increase in the bioavailability of metoprolol through inhibition of enzymes responsible for the first-pass elimination of the beta-blocker."	( The racemic metoprolol H2-antagonist interaction. Batra, H; Bowes, RJ; Davidson, EM; Garstang, FM; Rowland, M; Toon, S, 1988)	0.91
" There were no differences in half-life, systemic clearance or bioavailability (f)."	( Influence of smoking and gender on the disposition kinetics of metoprolol. Campbell, SC; Mayersohn, MB; Perrier, DG; Schaaf, LJ; Vagedes, T, 1987)	0.51
"The concomitant administration of hydralazine with metoprolol or propranolol substantially increases the oral bioavailability of these beta-blockers, presumably via reduction of the first-pass effect."	( Effect of hydralazine on the elimination of antipyrine in the rat. Knowlton, PW; Svensson, CK; Ware, JA, 1987)	0.52
" The absorption rate of metoprolol perfused in the jejunum in a saline solution appeared to be lower than that observed after gastric administration of the drug incorporated in a meal."	( Investigation of drug absorption from the gastrointestinal tract of man. II. Metoprolol in the jejunum and ileum. Bernier, JJ; Duval, M; Evard, D; Godbillon, J; Hirtz, J; Rongier, M; Schoeller, JP; Vidon, N, 1985)	0.81
"The influence of nutrients and digestive secretions on the intestinal absorption and bioavailability of the beta-adrenoceptor antagonist, metoprolol, was investigated in an isolated segment of jejunum using an intestinal perfusion technique."	( Investigation of drug absorption from the gastrointestinal tract of man. IV. Influence of food and digestive secretions on metoprolol jejunal absorption. Bernier, JJ; Bovet, M; Duval, M; Evard, D; Godbillon, J; Hirtz, J; Schoeller, JP; Vidon, N, 1985)	0.68
" The appearance of drug in plasma was delayed for both treatments, and for Oros the apparent absorption rate slowed 6 h after dosing."	( Influence of site of drug delivery on the systemic availability of metoprolol: comparison of intragastric infusion and 14/190 Oros administration. Barclay, SP; Good, W; John, VA; Shotton, PA; Wardle, HM; Warrington, SJ, 1985)	0.51
" There were no significant differences in the extent of bioavailability or rate of elimination of the drug between the 2 groups."	( Pharmacokinetic and pharmacodynamic properties of metoprolol in patients with impaired renal function. Attman, PO; Aurell, M; Johansson, L; Johnsson, G; Jordö, L; Regårdh, CG, )	0.38
" 2 Cimetidine caused no significant changes in the bioavailability of any of the two beta-adrenoceptor blockers and the rate of elimination of metoprolol was unaffected by the histamine H2-receptor blocker."	( The effect of pretreatment with cimetidine on the bioavailability and disposition of atenolol and metoprolol. Houtzagers, JJ; Regårdh, CG; Streurman, O, 1982)	0.68
"The bioavailability of metoprolol was studied in eight healthy young and seven healthy elderly volunteers."	( Bioavailability of metoprolol in young adults and the elderly, with additional studies on the effects of metoclopramide and probanthine. Briant, RH; Dorrington, RE; Ferry, DG; Paxton, JW, 1983)	0.9
" The technique was applied in a study of the bioavailability of metoprolol after oral administration to man; mean plasma concentrations are reported."	( Gas chromatographic determination of metoprolol in human plasma. Leroux, F; Sandrenan, N; Sioufi, A, 1983)	0.78
" It is concluded that the negative effect of the antacid on the bioavailability of atenolol is caused by a reduction in the in vivo dissolution rate due to increased gastric pH."	( The effect of antacid, metoclopramide, and propantheline on the bioavailability of metoprolol and atenolol. Lundborg, P; Persson, BA; Regårdh, CG, )	0.36
" This increase may be associated with a change in the bioavailability and/or clearance of the drug and is currently being investigated."	( A single and multiple dose pharmacokinetic and pharmacodynamic comparison of conventional and slow-release metroprolol. John, VA; Kendall, MJ; Quarterman, CP; Welling, PG, 1980)	0.26
" In the present experiments, 33 ketamine-anesthetized Sprague-Dawley rats were exposed to 2450-MHz microwaves at an average power density of 60 mW/sq cm (whole-body average specific absorption rate of approximately 14 W/kg) until death occurred."	( Microwave-induced lethal heat stress: effects of phentolamine, prazosin and metoprolol. Berger, RE; Chang, KS; Frei, MR; Jauchem, JR, 1995)	0.52
" The bioavailability of 7/95, 14/190 and 21/285 Oros tablets was compared to that of either 100 mg conventional or 200 mg slow-release Lopresor tablets in 3 two-period change over experiments."	( Stable isotope methodology for studying the performance of metoprolol Oros tablets in comparison to conventional and slow release formulations. Cardot, JM; Godbillon, J; Richard, J, )	0.37
"The absolute bioavailability of metoprolol (MP) was evaluated following oral and transdermal administration in hairless rats."	( Transdermal delivery of metoprolol. II: In-vitro skin permeation and bioavailability in hairless rats. Adir, J; Ghosh, TK; Onyilofur, S; Xiang, SL, 1995)	0.88
"The relative bioavailability of metoprolol and pindolol from capsules containing the drug preadsorbed onto activated charcoal (100 mg metoprolol tartrate/120 mg charcoal and 10 mg pindolol/20 mg charcoal) was studied in two separate studies, in healthy volunteers, using randomized, crossover designs."	( The bioavailability of two beta-blockers preadsorbed onto charcoal. Neuvonen, PJ; Ojala-Karlsson, P; Roivas, L, 1994)	0.57
"The bioavailability and pharmacodynamic bioequivalence of a conventional and an experimental sustained-release formulation of 100 mg metoprolol tartrate were studied in a randomised cross-over study in seven healthy volunteers by assessing over 24 h the plasma kinetics of R,S-metoprolol, its beta 1-adrenoceptor binding component, and by determining the extent to which the active drug moiety in plasma occupied rabbit lung beta 1- and rat reticulocyte beta 2-adrenoceptors."	( Receptor binding assays in analysing the bioavailability and pharmacodynamic bioequivalence of active drug moieties. A study of metoprolol. Kaila, T; Neuvonen, PJ; Roivas, L, 1994)	0.7
"Steady-state bioavailability and day-to-day variability of plasma levels were evaluated in 18 healthy male subjects in a crossover study of multiple once-daily administration of two novel oral drug delivery systems of metoprolol and an immediate-release tablet (100 mg metoprolol tartrate)."	( Steady-state bioavailability and day-to-day variability of a multiple-unit (CR/ZOK) and a single-unit (OROS) delivery system of metoprolol after once-daily dosing. Abrahamsson, B; Bergstrand, R; Olofsson, B; Sandberg, A; Svenheden, A, 1993)	0.68
" The primary pharmacokinetic characteristics for extent and rate of absorption were AUC(0-24h) and % PTF, respectively."	( Pantoprazole has no influence on steady state pharmacokinetics and pharmacodynamics of metoprolol in healthy volunteers. Bliesath, H; Hartmann, M; Huber, R; Koch, HJ; Mascher, H; Steinijans, VW; Wurst, W, 1996)	0.52
"The bioavailability patterns of a 100 mg metoprolol controlled release tablet and a 10 mg bisoprolol normal release tablet were compared in a single dose crossover study in 12 healthy subjects."	( Comparative bioavailability of a metoprolol controlled release formulation and a bisoprolol normal release tablet after single oral dose administration in healthy volunteers. Demblon, C; Deroubaix, X; Jeanbaptiste, B; Lens, S; Lins, RL; Poelaert, D; Stockis, A, 1996)	0.84
" The therapeutic time interval may be modulated influencing the rate of absorption by controlling dissolution rate and changing the transport through the membranes."	( [Role of mass transfer processes in drug formulation]. Antal, I; Csóka, G; Marton, S; Plachy, J; Rácz, I, 1996)	0.29
"A reverse-phase High Performance Liquid Chromatographic (HPLC) method was developed for the analysis of metoprolol in the large number of human plasma samples obtained in in vitro-in vivo correlations (IVIVC) and bioavailability studies of extended release formulations of metoprolol tartrate."	( A sensitive assay of metoprolol and its major metabolite alpha-hydroxy metoprolol in human plasma and determination of dextromethorphan and its metabolite dextrorphan in urine with high performance liquid chromatography and fluorometric detection. Eddington, NE; Leslie, J; Mistry, B, 1998)	0.83
" To examine the impact of formulation and processing variables on in vivo absorption, three batches were selected for a bioavailability study based on their dissolution profiles."	( Evaluation of in vitro release rate and in vivo absorption characteristics of four metoprolol tartrate immediate-release tablet formulations. Augsburger, LL; Eddington, ND; Fossler, MJ; Lesko, LJ; Rekhi, GS; Schwartz, P, 1997)	0.52
" The average percent prediction error of less than 10% indicates that the correlation is predictive and allows the associated dissolution data to be used as a surrogate for bioavailability studies."	( Development and internal validation of an in vitro-in vivo correlation for a hydrophilic metoprolol tartrate extended release tablet formulation. Augsburger, L; Eddington, ND; Hussain, A; Marroum, P; Uppoor, R, 1998)	0.52
"A study was conducted to compare the in vivo bioavailability of a generic metoprolol tablet preparation (Metoprolol) with that of the innovator product, Betaloc."	( Pharmacokinetic and bioequivalent study of a generic Metoprolol tablet preparation. Chan, KL; Peh, KK; Toh, WT; Yuen, KH, 1998)	0.78
" Metoprolol showed a considerable rectal bioavailability (AUC, C max) and was absorbed quickly from the rectum (T max)."	( The relative bioavailability of metoprolol following oral and rectal administration to volunteers and patients. Beysens, AJ; de Stoppelaar, FM; Gorgels, AP; Stappers, JL; Stolk, LM, 1999)	1.5
"The quantitative structure-bioavailability relationship of 232 structurally diverse drugs was studied to evaluate the feasibility of constructing a predictive model for the human oral bioavailability of prospective new medicinal agents."	( QSAR model for drug human oral bioavailability. Topliss, JG; Yoshida, F, 2000)	0.31
" The new methodology may, therefore, be used for fast bioavailability screening of virtual libraries having millions of molecules."	( Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. Ertl, P; Rohde, B; Selzer, P, 2000)	0.31
"This paper describes a graphical model for simplifying in vitro absorption, metabolism, distribution, and elimination (ADME) data analysis through the estimation of oral bioavailability (%F) of drugs in humans and other species."	( Graphical model for estimating oral bioavailability of drugs in humans and other species from their Caco-2 permeability and in vitro liver enzyme metabolic stability rates. Hwang, KK; Mandagere, AK; Thompson, TN, 2002)	0.31
"This study evaluated the effects of batch size on the in vitro dissolution and the in vivo bioavailability of immediate release formulations of propranolol hydrochloride and metoprolol tartrate."	( Scale-up effects on dissolution and bioavailability of propranolol hydrochloride and metoprolol tartrate tablet formulations. Augsburger, LL; Eddington, ND; Lesko, LJ; Rekhi, GS, 2000)	0.72
" Addition of dronedarone (800-1600 mg daily) to metoprolol (200 mg daily) increases bioavailability of metoprolol in CYP2D6 extensive metabolizers and induces an additive dronedarone dose-dependent negative inotropic effect."	( Pharmacokinetic and pharmacodynamic interactions between metoprolol and dronedarone in extensive and poor CYP2D6 metabolizers healthy subjects. Caplain, H; Damy, T; Hulot, JS; Lechat, P; Pousset, F, 2004)	0.82
"To investigate the mechanism responsible for the increased bioavailability of propranolol in bilateral ureter-ligated (BUL) rats, the intestinal absorption and hepatic extraction of propranolol and metoprolol were evaluated."	( Intestinal absorption and hepatic extraction of propranolol and metoprolol in rats with bilateral ureteral ligation. Hashimoto, Y; Higashi, T; Ohta, T; Okabe, H, 2004)	0.75
" The delayed T(max) lower C(max) decreased K(a) unaltered bioavailability and prolonged t(1/2) indicated a slow and prolonged release of metoprolol tartrate from guar gum three-layer matrix tablets in comparison with the immediate release tablet dosage form."	( Pharmacokinetic evaluation of guar gum-based three-layer matrix tablets for oral controlled delivery of highly soluble metoprolol tartrate as a model drug. Al-Saidan, SM; Bhaskar, P; Karthikeyan, RS; Krishnaiah, YS; Satyanarayana, V, 2004)	0.73
" The results suggest that the pharmacokinetic variability of metoprolol in Japanese extensive metabolizers of CYP2D6 is very large, probably because CYP2D6*10 is responsible not only for the decreased systemic clearance (CL) but also for the increased bioavailability (F) of the drug."	( Nonlinear mixed effects model analysis of the pharmacokinetics of metoprolol in routinely treated Japanese patients. Hashimoto, Y; Inoue, H; Mizumaki, K; Nozawa, T; Taguchi, M; Tahara, K; Takesono, C, 2004)	0.8
"To study the correlation between the absorption rate constants of beta-adrenoreceptor antagonists in rat small intestinal segments and their molecular structural parameters."	( [Correlation between absorption rates of beta-adrenoreceptor antagonists in rat small intestine and their molecular structures]. Fu, XC; Sun, Q, 2005)	0.33
"The absorption rate constants of beta-adrenoreceptor antagonists in rat jejunum or ileum were well linearly correlated with the sum of the net charges of all hydrogen atoms and the molecular volumes."	( [Correlation between absorption rates of beta-adrenoreceptor antagonists in rat small intestine and their molecular structures]. Fu, XC; Sun, Q, 2005)	0.33
"The absorption rate constants of beta-adrenoreceptor antagonists in rat small intestinal segments are mainly related with their lipophilicity,hydrogen-bonding potential and molecular size."	( [Correlation between absorption rates of beta-adrenoreceptor antagonists in rat small intestine and their molecular structures]. Fu, XC; Sun, Q, 2005)	0.33
" For such drugs, the bioavailability is influenced by the time of administration."	( Pharmacokinetics of an immediate release, a controlled release and a two pulse dosage form in dogs. Amidon, GL; Kim, JS; Löbenberg, R, 2005)	0.33
" The relative bioavailability of two FDA approved (Orange Book AB rating) solid oral dosage forms of metoprolol and propranolol/hydrochlorothiazide (combination tablets) was evaluated in human volunteers under fed conditions using a two-way crossover design."	( The effect of food on the relative bioavailability of rapidly dissolving immediate-release solid oral products containing highly soluble drugs. Asafu-Adjaye, E; Ciavarella, AB; Conner, DP; Faustino, PJ; Hussain, AS; Lesko, LJ; Mehta, MU; Parekh, A; Straughn, AB; Yang, Y; Yu, LX, )	0.35
"The FDA has published recommendations for sponsors who wish to request a waiver of in vivo bioavailability (BA) or bioequivalence (BE) studies for immediate release (IR) solid oral dosage forms based on the Biopharmaceutics Classification System (BCS)."	( The suitability of an in situ perfusion model for permeability determinations: utility for BCS class I biowaiver requests. Amidon, GL; Hilfinger, J; Kijek, P; Kim, JS; Mitchell, S; Tsume, Y, )	0.13
" These results suggested that the decreased CL/F of metoprolol in rats with glycerol-induced ARF is mainly a result of the increased initial absorption rate in the intestine followed by partial saturation of hepatic first-pass metabolism."	( Pharmacokinetics and hepatic extraction of metoprolol in rats with glycerol-induced acute renal failure. Hashimoto, Y; Taguchi, M; Taira, S; Tanabe, H, 2007)	0.85
" In this pharmacokinetics study, in which the patients acted as their own controls, we have evaluated the bioavailability of perioperative metoprolol tablets in CABG surgery patients."	( Does coronary artery bypass surgery affect metoprolol bioavailability. Gergov, M; Hakala, T; Kokki, H; Ojanperä, I; Ranta, VP; Valtola, A, 2007)	0.8
"This study indicates that the bioavailability of metoprolol is markedly reduced when administered in tablet form during the early phase after CABG."	( Does coronary artery bypass surgery affect metoprolol bioavailability. Gergov, M; Hakala, T; Kokki, H; Ojanperä, I; Ranta, VP; Valtola, A, 2007)	0.86
" Plasma concentrations found with terbutaline and metoprolol are presented showing that terbutaline has its best uptake in the upper small intestine, whereas metoprolol shows the same bioavailability along the whole gut."	( A convenient method for local drug administration at predefined sites in the entire gastrointestinal tract: experiences from 13 phase I studies. Abrahamsson, B; Borgå, O; Månsson, W; Nyberg, L; Seidegård, J, 2007)	0.59
" This study compares the bioavailability of metoprolol tartrate from a TDDS with that from a conventional marketed tablet in healthy human volunteers."	( Comparative bioavailability of metoprolol tartrate after oral and transdermal administration in healthy male volunteers. Ali, A; Aqil, M; Saha, N; Sultana, Y, 2007)	0.89
"A 3-fold improvement in bioavailability was observed with the TDDS form over oral therapy as shown by the extent of absorption indicated by the mean area under the concentration-time curve from time zero to time t values for tablets (451."	( Comparative bioavailability of metoprolol tartrate after oral and transdermal administration in healthy male volunteers. Ali, A; Aqil, M; Saha, N; Sultana, Y, 2007)	0.63
"To prepare transdermal drug delivery system (TDDS) of felodipine and metoprolol and to study its pharmaceutical characteristics, pharmacokinetics and bioavailability in rabbits, an HPLC assay was established for the simultaneous determination of felodipine and metoprolol in the permeation receptor and patch."	( [Preparation of transdermal drug delivery system of felodipine-metoprolol and its bioavailability in rabbits]. Fu, GY; Liu, ZY; Wang, R; Wang, WG; Yun, LH, 2007)	0.81
" The bioavailability of metoprolol tartrate after nasal administration of this powder to rabbits was compared with powders manufactured via other procedures: (a) freeze-drying of a dispersion prepared using the co-spray-dried powder, (b) freeze-drying of a dispersion prepared using a physical mixture of drug and mucoadhesive polymers."	( Effect on the nasal bioavailability of co-processing drug and bioadhesive carrier via spray-drying. Adriaensens, P; Carleer, R; Coucke, D; Foreman, P; Remon, JP; Vervaet, C, 2009)	0.66
" The observed changes in product stability may adversely affect the products bioavailability profile, even though the potency of the active drug remained within USP specification range of 90-110%."	( Comparative stability of repackaged metoprolol tartrate tablets. Carlin, AS; Ellison, CD; Faustino, PJ; Gupta, A; Khan, MA; Lyon, RC; Rothman, B; Yang, Y, 2010)	0.64
"Oral bioavailability (F) is a product of fraction absorbed (Fa), fraction escaping gut-wall elimination (Fg), and fraction escaping hepatic elimination (Fh)."	( Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination. Chang, G; El-Kattan, A; Miller, HR; Obach, RS; Rotter, C; Steyn, SJ; Troutman, MD; Varma, MV, 2010)	0.36
"The Biopharmaceutical Classification System (BCS) guidance issued by the FDA allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release (IR) solid oral dosage forms only for BCS class I drugs."	( The biowaiver extension for BCS class III drugs: the effect of dissolution rate on the bioequivalence of BCS class III immediate-release drugs predicted by computer simulation. Amidon, GL; Tsume, Y, 2010)	0.36
" To show the importance of physicochemical properties, the classic QSAR and CoMFA of neonicotinoids and prediction of bioavailability of pesticides in terms of membrane permeability in comparison with drugs are described."	( Importance of physicochemical properties for the design of new pesticides. Akamatsu, M, 2011)	0.37
"This study sought to determine if metoprolol succinate ER (MET), and nebivolol (NEB), a β1-AR with increased bioavailability of nitric oxide (NO), would have differing effects on plasma asymmetric dimethylarginine concentration in hypertensives."	( The effect of nebivolol versus metoprolol succinate extended release on asymmetric dimethylarginine in hypertension. Blackstock, C; Chen, W; Delafontaine, P; Giles, TD; Higashi, Y; Kandavar, R; Roffidal, LE; Sander, GE; Sukhanov, S; Vaughn, C, )	0.7
"5) and 30% (w/w) MPT had a low relative bioavailability compared with the commercial product Lopressor®, which significantly improved at higher MPT concentration (50%, w/w)."	( Sustained-release and swelling characteristics of xanthan gum/ethylcellulose-based injection moulded matrix tablets: in vitro and in vivo evaluation. De Beer, T; Mendez-Montealvo, G; Onofre, FO; Quinten, T; Remon, JP; Vervaet, C; Wang, YJ, 2011)	0.37
" The in vivo study of new SR tablets showed significant improvement in the oral bioavailability of MS in rabbits after a single oral dose of 25 mg."	( Modulation of drug (metoprolol succinate) release by inclusion of hydrophobic polymer in hydrophilic matrix. Bose, A; Khanam, J; Siddique, S, 2011)	0.69
" Nebivolol is a third-generation β-blocker that increases the bioavailability of nitric oxide."	( Differential effects of nebivolol and metoprolol on insulin sensitivity and plasminogen activator inhibitor in the metabolic syndrome. Ayers, K; Brown, NJ; Byrne, LM; DeMatteo, A, 2012)	0.65
"Metoprolol, a cardioselective β-blocker, is well absorbed in colon after oral administration with mean elimination half life of 3 h with bioavailability 50% due to extensive first pass effect, thus it was aimed to develop its modified release dosage form to reduce dosing frequency."	( Eudragit FS based colonic microparticls of metoprolol tartrate. Ahmad, M; Khan, HM; Khan, SA; Murtaza, G; Rasool, F, )	1.84
" The bioavailability of EVA 40 and 28 matrices in dogs was not significantly different, independent of PEO 7M concentration."	( Sustained release from hot-melt extruded matrices based on ethylene vinyl acetate and polyethylene oxide. Almeida, A; Bouquet, W; Brabant, L; De Beer, T; Remon, JP; Siepmann, F; Siepmann, J; Van Hoorebeke, L; Vervaet, C, 2012)	0.38
" On the other hand, following oral administration, pseudoephedrine fraction dose absorbed (F(abs)) and systemic bioavailability approaches 100%."	( Regional-dependent intestinal permeability and BCS classification: elucidation of pH-related complexity in rats using pseudoephedrine. Dahan, A; Fairstein, M; Swissa, R, 2013)	0.39
" The bioavailability of MPT, after oral administration to dogs as prills containing 30% and 40% MPT using behenic acid as matrix former, was not significantly different from a commercial sustained release reference formulation, although the 40% MPT prills showed a burst release."	( Prilling of fatty acids as a continuous process for the development of controlled release multiparticulate dosage forms. Adriaensens, P; Carleer, R; De Beer, T; De Geest, BG; Remon, JP; Saerens, L; Vervaeck, A; Vervaet, C, 2013)	0.39
" A clear influence of pH on the absorption was seen and a significant higher absolute bioavailability was obtained after buccal dosing (58-107%) compared to oral (3%) administration, ranging 58-107% and 3%, respectively."	( In vitro, ex vivo and in vivo examination of buccal absorption of metoprolol with varying pH in TR146 cell culture, porcine buccal mucosa and Göttingen minipigs. Andersen, MB; Garmer, M; Holm, R; Jacobsen, J; Jespersen, ML; Jørgensen, EB; Karlsson, JJ; Meng-Lund, E, 2013)	0.63
" The bioavailability of sustained release tablets, F7 was compared with commercially available tablets, MetXL50 in 12 healthy human volunteers in a crossover design."	( Compritol®888 ATO a lipid excipient for sustained release of highly water soluble active: formulation, scale-up and IVIVC study. Desai, NS; Farah, N; Gogtay, N; Jain, AS; Kadam, PP; Kapadia, CJ; Nagarsenker, MS; Patere, SN; Thatte, UM, 2013)	0.39
"We previously reported that aging and/or cytochrome P450 2D6 polymorphism are responsible for the interindividual variability in the systemic clearance (CL) and bioavailability (F) of metoprolol."	( Variability of bioavailability and intestinal absorption mechanisms of metoprolol. Fukao, M; Hashimoto, Y; Horie, A; Inoue, H; Ishida, K; Nozawa, T; Taguchi, M, 2014)	0.83
" In conclusion, this study suggests that the increase of the bioavailability of propranolol in ESRD is partly induced by the inhibition of the hepatic metabolism of CYP1A2 by xanthine in the uremic serum."	( Possibility of decrease in CYP1A2 function in patients with end-stage renal disease. Furukubo, T; Izumi, S; Minegaki, T; Nagatomo, M; Nishiguchi, K; Sugimoto, S; Tsujimoto, M; Yamakawa, T, 2014)	0.4
"Metoprolol succinate is a very potent drug for the treatment of hypertension but suffers from poor bioavailability due to its erratic absorption in lower GI tract."	( Bilayer mucoadhesive microparticles for the delivery of metoprolol succinate: Formulation and evaluation. Dhawan, N; Kumar, K; Patwal, PS; Sharma, H; Vaidya, B; Vaidya, S, 2015)	2.11
" It was found that there is a significant increase in the bioavailability of metoprolol succinate from BG formulation which was evident from the high AUC and MRT values compared with the commercial formulation."	( Badam gum: a natural polymer in mucoadhesive drug delivery. Design, optimization, and biopharmaceutical evaluation of badam gum-based metoprolol succinate buccoadhesive tablets. Beeravelli, S; Kolapalli, VR; Medikonda, J; Mylangam, CK; Pidaparthi, JS, 2016)	0.87
" The absorption rate coefficients of all the assayed compounds did not show statistically significant differences between male and female rats consequently all the individual values were combined to compare between reabsorption methods."	( Validation of phenol red versus gravimetric method for water reabsorption correction and study of gender differences in Doluisio's absorption technique. Bermejo, M; Gonzalez-Alvarez, I; Gonzalez-Alvarez, M; Tuğcu-Demiröz, F, 2014)	0.4
" Though several lipophilic derivatives of CPT have shown interesting oral bioavailability in preclinical and clinical studies, only Topotecan has been approved for this route of administration."	( A promising camptothecin derivative: Semisynthesis, antitumor activity and intestinal permeability. Bermejo, M; Corma, A; Díaz Cabañas, MJ; García-Giménez, JL; Gonzalez-Alvarez, I; Gonzalez-Alvarez, M; Mangas-Sanjuán, V; Rodríguez-Berna, G, 2014)	0.4
" Compared to a fixed-dose reference, oral co-administration of the MPT and HCT prills to dogs yielded a similar bioavailability for the HCT prills, while the MPT prills resulted in a significant higher bioavailability."	( Prilling as manufacturing technique for multiparticulate lipid/PEG fixed-dose combinations. De Beer, T; Monteyne, T; Remon, JP; Saerens, L; Vervaeck, A; Vervaet, C, 2014)	0.4
"The aim of the present study was to evaluate the disposition of metoprolol after oral administration of an immediate and controlled-release formulation before and after Roux-en-Y gastric bypass (RYGB) surgery in the same individuals and to validate a physiologically based pharmacokinetic (PBPK) model for predicting oral bioavailability following RYGB."	( Drug disposition and modelling before and after gastric bypass: immediate and controlled-release metoprolol formulations. Augustijns, P; Darwich, AS; de Hoon, J; Foulon, V; Gesquiere, I; Lannoo, M; Matthys, C; Rostami, A; Van der Schueren, B, 2015)	0.87
" The intestinal absorption rate for each drug was acquired by deconvolution, using historical intravenous data as reference, and used with the intestinal surface area and the dose remaining in the lumen to estimate the Peff."	( Human in vivo regional intestinal permeability: quantitation using site-specific drug absorption data. Dahlgren, D; Lennernäs, H; Roos, C; Sjögren, E, 2015)	0.42
" Bioavailability of midazolam was 4% in marmosets, presumably because of contribution of marmoset P450 3A4 expressed in small intestine and liver, with a high catalytic efficiency for midazolam 1'-hydroxylation as evident in the recombinant system."	( Simultaneous pharmacokinetics evaluation of human cytochrome P450 probes, caffeine, warfarin, omeprazole, metoprolol and midazolam, in common marmosets (Callithrix jacchus). Inoue, T; Sasaki, E; Shimizu, M; Toda, A; Uehara, S; Uno, Y; Utoh, M; Yamazaki, H, 2016)	0.65
" Metoprolol and Verapamil absorption rate coefficients were determined using the in situ closed loop perfusion model in four strains of rats and in both genders."	( Drug gastrointestinal absorption in rat: Strain and gender differences. Bermejo, M; Colon-Useche, S; González-Álvarez, I; González-Álvarez, M; Mangas-Sanjuan, V; Oltra-Noguera, D, 2015)	1.33
" Standard bioavailability variables were determined."	( Validation of the IntelliCap® system as a tool to evaluate extended release profiles in human GI tract using metoprolol as model drug. Abrahamsson, B; Erlandsson, F; Iordanov, V; Söderlind, E; von Corswant, C; Wanke, C, 2015)	0.63
" As a consequence of these CYP2D6 metabolizer phenotypes, pharmacokinetics and bioavailability of carvedilol and metoprolol can range from therapeutically ineffective levels (in the UM patients) to excessive (overdose) and potentially toxic concentrations (in PM patients)."	( Impact of CYP2D6 Genetic Variation on the Response of the Cardiovascular Patient to Carvedilol and Metoprolol. Brill, A; Lymperopoulos, A; McCrink, KA, 2015)	0.84
" Pharmacokinetic study performed in rabbit model showed that the relative oral bioavailability of MT after administration of oral solution, sustain release and optimized formulation was 51%, 67% and 87%, respectively."	( Tapioca starch blended alginate mucoadhesive-floating beads for intragastric delivery of Metoprolol Tartrate. Biswas, N; Sahoo, RK, 2016)	0.66
" The similar absorption rate between felodipine and metoprolol in beagles was also obtained by this osmotic pump formulation."	( Synchronous delivery of felodipine and metoprolol tartrate using monolithic osmotic pump technology. Di, Z; Li, Y; Li, Z; Liu, N; Liu, Y; Mei, X; Yan, K; Yang, Y; Yang, Z; Yu, F; Zhang, H; Zhao, S, 2016)	0.95
"The development of oral modified-release (MR) dosage forms requires an active pharmaceutical ingredient (API) with a sufficiently high absorption rate in both the small and large intestine."	( Regional Intestinal Permeability in Dogs: Biopharmaceutical Aspects for Development of Oral Modified-Release Dosage Forms. Abrahamsson, B; Dahlgren, D; Johansson, P; Lennernäs, H; Lundqvist, A; Roos, C; Sjögren, E; Tannergren, C, 2016)	0.43
" Niosomes were utilized to allow for prolonged release of the drug, whereas the films were used to increase the drug's bioavailability via the sublingual route."	( Sublingual fast dissolving niosomal films for enhanced bioavailability and prolonged effect of metoprolol tartrate. Allam, A; Fetih, G, 2016)	0.65
"98) was obtained when comparing apparent permeability coefficient to the absolute bioavailability of metoprolol administered buccally to mini-pigs."	( Use of Permeapad® for prediction of buccal absorption: A comparison to in vitro, ex vivo and in vivo method. Bauer-Brandl, A; Bibi, HA; Holm, R, 2016)	0.65
" In the present study, the effects of gallic acid and ellagic acid pretreatment on intestinal transport and oral bioavailability of metoprolol were investigated."	( Enhanced oral bioavailability of metoprolol with gallic acid and ellagic acid in male Wistar rats: involvement of CYP2D6 inhibition. Athukuri, BL; Neerati, P, 2016)	0.92
" The bioavailability study was conducted to evaluate the pharmacokinetic parameters of orally administered metoprolol in rats."	( Enhanced oral bioavailability of metoprolol with gallic acid and ellagic acid in male Wistar rats: involvement of CYP2D6 inhibition. Athukuri, BL; Neerati, P, 2016)	0.93
"Gallic acid and ellagic acid significantly enhanced the oral bioavailability of metoprolol by inhibiting CYP2D6-mediated metabolism in the rat liver."	( Enhanced oral bioavailability of metoprolol with gallic acid and ellagic acid in male Wistar rats: involvement of CYP2D6 inhibition. Athukuri, BL; Neerati, P, 2016)	0.94
"Short-term fasting can alter drug exposure but it is unknown whether this is an effect of altered oral bioavailability and/or systemic clearance."	( Effect of Short-Term Fasting on Systemic Cytochrome P450-Mediated Drug Metabolism in Healthy Subjects: A Randomized, Controlled, Crossover Study Using a Cocktail Approach. Achterbergh, R; Lammers, LA; Mathôt, RAA; Romijn, JA; van Schaik, RHN, 2017)	0.46
" The high throughput, accurate and sensitive method for FDP and MPL was validated and applied to the bioavailability research of FDP and MPL in beagle dogs."	( Simultaneous Determination of Felodipine and Metoprolol in Beagle Dog Plasma by Online SPE-LC-MS/MS and Its Application in a Pharmacokinetic Study. Chen, M; Li, Y; Liu, Y; Mei, L; Mei, X; Xie, X; Yang, Y; Yu, F; Zhou, J, 2017)	0.71
"Cardiac surgery and conventional extracorporeal circulation (CECC) impair the bioavailability of drugs administered by mouth."	( How do different extracorporeal circulation systems affect metoprolol bioavailability in coronary artery bypass surgery patients. Ellam, S; Halonen, J; Hartikainen, J; Kokki, H; Lindberg, O; Maaroos, M; Ojanperä, I; Ranta, M; Ranta, VP; Tolonen, A; Viitala, M, 2018)	0.72
"The bioavailability of metoprolol by mouth was markedly reduced in the early phase after CABG with no difference between the CECC-, MECC-, and OPCAB-groups."	( How do different extracorporeal circulation systems affect metoprolol bioavailability in coronary artery bypass surgery patients. Ellam, S; Halonen, J; Hartikainen, J; Kokki, H; Lindberg, O; Maaroos, M; Ojanperä, I; Ranta, M; Ranta, VP; Tolonen, A; Viitala, M, 2018)	1.03
"The aim of my study was to find the effect of co-administrating orange juice and hesperidin on the bioavailability of metoprolol tartrate in rabbits."	( Role of hesperidin and fresh orange juice in altering the bioavailability of beta-blocker, metoprolol tartrate. An Batool Rizvi, SN; Firdous, S; Hussain, N; Naeem, M; Salam, R; Zaheer, M, 2022)	1.15

Excerpt	Relevance	Reference
" The results indicate that metoprolol in a dosage of 150-450 mg daily is an effective and well tolerated therapy both in patients previously untreated and in patients unsatisfactorily treated with other antihypertensive agents."	( Antihypertensive effect and tolerability of metoprolol during long-term treatment: a multicentre study. Rosengard, S, 1977)	0.82
" Dose-response curves of isoprenaline were constructed in nine hypertensive patients before and after either propranolol or metoprolol."	( Effect of selective and non-selective beta-adrenoreceptor blockade on calf blood flow in hypertensive patients. Clement, DL, 1978)	0.47
" Follow-up a year later produced no evidence of unusual side effects but there was a reduction in the mean daily dosage without loss of efficacy."	( The first year of metroprolol (Lopresor): an analysis of a newly released drug in general practice. Duncan, T; Stephens, EJ, 1979)	0.26
" It is important to know how the pharmacokinetics of a drug vary with different disease states so that appropriate adjustments to dosage can be made."	( Series on pharmacology in practice. 2. Antiarrhythmic drug therapy. Federman, J; Vlietstra, RE, 1979)	0.26
" In terms of the chronotropic effect, this dose of metoprolol produced a substantial shift to the right of the dose-response curve to isoprenaline; substantial reductions of arterial pressure (10%), cardiac output (21%), aortic blood acceleration (13%), left ventricular dP/dt max (13%) and left ventricular power (25%) were observed."	( Effects of metoprolol on systemic haemodynamics, myocardial performance and the coronary circulation during halothane anaesthesia. Burt, G; Foëx, P, 1979)	0.9
" The mean resting blood pressures were 168/108 mmHg, 151/98 mmHg and 150/96 mmHg at pre-trial, after the twice-daily dosage period and after the once-daily dosage period, respectively."	( A fixed combination of metoprolol and hydrochlorothiazide for hypertension: a multi-centre study. Goodfellow, RM, 1979)	0.57
" Midway through each four-week period, drug dosage was doubled; thus, regimes were metoprolol, 150 and 300 mg/day, propranolol, 120 and 240 mg per day and placebo, 3 and 6 tablets per day."	( Assessment of metoprolol, a cardioselective beta-blocking agent, during chronic therapy in patients with angina pectoris. Borer, JS; Comerford, MB; Sowton, E, 1976)	0.84
" The optimal dose should be determined on a case-by-case basis, by increasing the daily dosage gradually."	( [Beta-blockers and migraine]. Bousser, MG; Massiou, H, 1992)	0.28
" Four pts (6%) did not tolerate the first test dosage of metoprolol and twenty-two patients were excluded from analysis because of inadequate follow-up or because they were enrolled in an international trial."	( [Beta blocking agents in the treatment of dilated cardiomyopathy: review of the literature and clinical experience with 67 patients]. Camerini, F; Di Lenarda, A; Lardieri, G; Mestroni, L; Miani, D; Perkan, A; Pinamonti, B; Sinagra, G, 1992)	0.53
" Selection of the dosage was individual under the control of circulation parameters."	( [The action of the new beta-adrenoblocker Lopressor on the hemodynamics of hypertension patients]. Maev, IV; V'iuchnova, ES, 1992)	0.28
"The anti-ischemic efficacy of diltiazem may improve with increments in dosage and with additional beta-blocking therapy."	( Acute hemodynamic and electrophysiologic effects and safety of high-dose intravenous diltiazem in patients receiving metoprolol. Kruijssen, DA; Look, MP; Remme, WJ; van Hoogenhuyze, DC; Wiesfeld, AC, 1992)	0.49
" Blood glucose increased in metoprolol treated healthy and liver damaged rats after a single dosage likewise following prolonged treatment."	( Metoprolol and propranolol treatment in carbon tetrachloride-induced hepatic injury. Kulcsár, A; Kulcsár-Gergely, J, 1992)	2.02
" During chronic therapy, at the end of the dosing interval (12 hours), significant decreases in BP persisted with minimal changes in the other variables."	( Antihypertensive effect of felodipine associated with persistent sympathetic activation and minimal regression of left ventricular hypertrophy. Holliwell, DL; Leenen, FH, 1992)	0.28
" This phenomenon contributes to the normal dose-response curve for epinephrine, according to our analysis, but only in combination with the apparent high efficiency of the receptor in the epinephrine-bound state at cyclase activation."	( Comparisons of the combined contributions of agonist binding frequency and intrinsic efficiency to receptor-mediated activation of adenylate cyclase. Barber, R; Stickle, D, 1991)	0.28
"General well-being, adverse effects and anti-hypertensive efficacy have been investigated in a double blind, parallel-group, dose-response multicentre study of diltiazem and metoprolol monotherapy for hypertension."	( Effects of diltiazem and metoprolol on blood pressure, adverse symptoms and general well-being. The Swedish Diltiazem-Metoprolol Multi-Centre Study Group. Dahlöf, C; Gustafsson, S; Hedner, T; Olsson, SO; Thulin, T, 1991)	0.78
" 20 of them suffered from essential hypertension (group A) and were treated with metoprolol with a dosage of 50 to 200 mg per day."	( [Effect of metoprolol on microcirculation and blood viscoelasticity]. Eber, O; Klima, G; Költringer, P; Langsteger, W; Lind, P; Pierer, G; Reisecker, F, 1991)	0.9
" Numerous questions concerning the exact indications of these drugs, the nature and dosage of the beta-blocker to be used, the possible combinations with other therapies and the responses to be expected remain to be answered."	( [Beta-blockers in the treatment of heart failure]. Grosgogeat, Y; Komajda, M; Lechat, P; Salloum, J, 1990)	0.28
" In a double-blind dose-finding study, 58 patients were treated in five consecutive dosage steps each lasting 1-3 months."	( Responders and non-responders to metoprolol, propranolol and nifedipine treatment in migraine prophylaxis: a dose-range study based on time-series analysis. Diener, HC; Gerber, WD; Niederberger, U; Scholz, E, 1991)	0.56
" Three hours after dosing beta-adrenoceptor blocker treatments significantly reduced exercise heart rate, prolonged time to complete exercise, and increased subjective fatigue measured by visual analogue scale."	( Influence of debrisoquine oxidation phenotype on exercise tolerance and subjective fatigue after metoprolol and atenolol in healthy subjects. Jackson, PR; Lennard, MS; Lewis, RV; Ramsay, LE; Tucker, GT; Yeo, WW, 1991)	0.5
" The metoprolol CR/ZOK preparation provides reproducible dissolution and absorption properties resulting in stable plasma concentrations with minimum fluctuations over a 24-hour dosage interval."	( Pharmacokinetic and biopharmaceutic aspects of once daily treatment with metoprolol CR/ZOK: a review article. Abrahamsson, B; Bergstrand, R; Regårdh, CG; Sandberg, A; Wieselgren, I, 1990)	1.02
"In a randomized double-blind multicenter study in 100 hypertensive patients, the effect of once daily (od) dosing with a new controlled release (CR/ZOK) formulation of metoprolol was compared with that of twice daily (bid) dosing with metoprolol conventional tablets."	( A comparison of a controlled release (CR/ZOK) formulation of metoprolol, once daily, with conventional metoprolol tablets, twice daily, in mild to moderate hypertension. Carruthers, G; Moore, M; Shearer, R; Taylor, W, 1990)	0.72
" Study I: The impact of metoprolol CR/ZOK 50 mg once daily for 4 weeks compared with placebo 24 hours post dosing was to produce a significant reduction in supine (P = ."	( The efficacy of low dose metoprolol CR/ZOK in mild hypertension and in elderly patients with mild to moderate hypertension. Baandrup, S; Houtzagers, J; Jäättelä, A; Westergren, G, 1990)	0.89
"Cardioselectivity of a single oral dose of metoprolol oral osmotic (OROS) (14/190 mg) and atenolol (100 mg) was compared in 12 patients with reversible obstructive airway disease by assessing the dose-response curve to increasing doses of inhaled salbutamol."	( Comparative evaluation of cardioselectivity of metoprolol OROS and atenolol: a double-blind, placebo-controlled crossover study. Bruni, B; Dottorini, ML; Grassi, V; Lecaillon, JB; Motolese, M; Peccini, F; Sorbini, CA; Tantucci, C, 1990)	0.8
" The results suggest that metoprolol can be safely used and offers the advantages of desired clinical response, shorter preoperative preparation time, simplicity of dosage and shorter postoperative hospital stay in comparison to propranolol for preoperative treatment of hyperthyroidism."	( The role of selective beta 1-blocker in the preoperative preparation of thyrotoxicosis: a comparative study with propranolol. Arya, R; Garg, KM; Godha, U; Jain, S; Mathur, P; Vickers, P, )	0.43
" No dosage adjustment of felodipine seems to be necessary in patients with hypertension and renal impairment."	( Acute and steady-state pharmacokinetics and antihypertensive effects of felodipine in patients with normal and impaired renal function. Aberg, J; Gelin, A; Karlberg, BE; Larsson, R; Regårdh, CG, 1990)	0.28
" The trough plasma concentration, Cmin, was significantly higher after 100 mg metoprolol CR/ZOK compared to CT dosed once daily; CminS were comparable between the two preparations in the 200 mg and 300 mg studies and lower after metoprolol CR/ZOK in the 400 mg study (278 nmol/L vs 469 nmol/L)."	( Pharmacokinetic and pharmacodynamic comparison of metoprolol CR/ZOK once daily with conventional tablets once daily and in divided doses. Bergstrand, R; Lücker, P; Moore, G; Olofsson, B; Wieselgren, I, 1990)	0.76
" The total effect over a dosage interval, defined as area under the effect curve, was significantly higher for metoprolol CR/ZOK compared to conventional tablets (90% confidence limits: 123-213%)."	( Pharmacokinetic and pharmacodynamic evaluation of metoprolol controlled release (CR/ZOK) 50 mg in young subjects. Bergstrand, R; Lundborg, P; Olofsson, B; Sandberg, A; Wieselgren, I, 1990)	0.74
" At the start and the end of the dosing interval, the CR/ZOK formulation was significantly more effective (P less than ."	( A pharmacokinetic and pharmacodynamic comparison of metoprolol CR/ZOK with a conventional slow release preparation. Jonkman, J; Oosterhuis, B; Sollie, F; Zuiderwijk, P, 1990)	0.53
" Lidocaine dosage was 2 mg/kg followed by a 70 micrograms/kg/min infusion and metoprolol dosage was a 75 micrograms/kg bolus."	( Interaction of metoprolol and lidocaine on the ventricular fibrillation threshold in the anesthetized dog. Balke, CW; de Langen, CD; Levine, JH; Moore, EN; Spear, JF, 1988)	0.86
" They were submitted to clinical exam, stress testing and plasma lipids dosage before and after four weeks of treatment."	( [Effect of beta blockers with intrinsic sympathomimetic activity on blood pressure and blood lipids in patients with essential hypertension]. Bellotti, G; Braga, A; Pileggi, F; Santomauro, A; Serro-Azul, JB; Serro-Azul, LG; Wajngarten, M; Yazbek Júnior, P, 1989)	0.28
" The amounts of metoprolol and alpha-hydroxy metoprolol excreted in 0-8 h urine collection, after dosing with 100 mg metoprolol, were measured and the metabolic ratio (% dose excreted as metoprolol/% dose excreted as alpha-hydroxy metoprolol) calculated."	( Metoprolol alpha-hydroxylation polymorphism in the San Bushmen of southern Africa. Avenant, J; Moncrieff, J; Sommers, DK, 1989)	2.07
"02) and practically unchanged after metoprolol, at a time and at a drug dosage when only minor changes in blood pressure and serum lipids were detectable."	( Adrenergic blocking agents and lipoprotein lipase activity. De Simone, B; Ferrara, LA; Leccia, G; Marotta, T; Rubba, P; Soro, S, 1989)	0.55
" However, as dosage adjustment and close observation may be necessary to minimise side effects, the use of this combination should be limited to hospital practice."	( Tolerability of combined treatment with verapamil and beta-blockers in angina resistant to monotherapy. McGourty, JC; Silas, JH; Solomon, SA, 1985)	0.27
" If standard doses of beta-blockers are used in PM subjects, they may be susceptible to concentration-related adverse reactions and they may also require lower and less frequent dosing for control of angina pectoris."	( Oxidation phenotype and the metabolism and action of beta-blockers. Lennard, MS, 1985)	0.27
" If standard doses of beta-blockers are used in poor metabolisers, these subjects may be susceptible to concentration-related adverse reactions and they may also require less frequent dosing for control of angina pectoris."	( The polymorphic oxidation of beta-adrenoceptor antagonists. Clinical pharmacokinetic considerations. Lennard, MS; Tucker, GT; Woods, HF, )	0.13
" PRA activity was significantly and markedly reduced by both bunolol and metoprolol shortly after dosing at a time when HR was significantly reduced but MBP was not."	( Antihypertensive effects of 12 beta adrenoceptor antagonists in conscious spontaneously hypertensive rats: relationship to changes in plasma renin activity, heart rate and sympathetic nerve function. Antonaccio, MJ; DeForrest, JM; High, J; Sybertz, E, 1986)	0.5
" If standard doses of some beta-blockers are used in poor metabolizers, these patients may be susceptible to concentration-related adverse reactions and they may also require lower and less frequent dosing for control of angina pectoris."	( Debrisoquine polymorphism and the metabolism and action of metoprolol, timolol, propranolol and atenolol. Lennard, MS; Silas, JH; Tucker, GT; Woods, HF, 1986)	0.51
" The dose-response relationship using individual maximal reduction of ET showed, on a molar basis, that bisoprolol is about 5, 7 and 10 times more effective than propranolol, atenolol and metoprolol, respectively."	( Pharmacodynamic profile of bisoprolol, a new beta 1-selective adrenoceptor antagonist. Bühring, KU; Leopold, G; Pabst, J; Simane, Z; Ungethüm, W; Wiemann, H, 1986)	0.46
" Blood pressure, ventricular rate, and echocardiographically determined ejection fraction, ejection time, and mean rate of circumferential fiber shortening (mVcf) were measured before dosing and at multiple time points during 10 hours after each dose, with subjects maintained in the supine position."	( Pharmacodynamic comparison of L-bunolol with propranolol, metoprolol, and placebo. Bahrmann, H; Greenblatt, DJ; Labedzki, L; Ochs, HR, 1988)	0.52
" Its hemodynamic profile was compared in a dose-response study with that of metoprolol, which is also cardioselective but lacks cardiostimulatory activity."	( Comparative effects of metoprolol and celiprolol on cardiac hemodynamics and left ventricular volume at rest and during exercise-induced angina. Frais, MA; Reynolds, G; Silke, B; Taylor, SH; Verma, SP, 1986)	0.81
" In controlled double-blind studies involving approximately 550 patients on doxazosin 1-16 mg once daily, significant reductions in both standing and supine BP were maintained throughout the 24 h dosing interval."	( The antihypertensive effects of doxazosin: a clinical overview. Cox, DA; Leader, JP; Milson, JA; Singleton, W, 1986)	0.27
" Although a twice daily dosage regimen is normally used, satisfactory control can be maintained in many patients with single daily doses of conventional or, more frequently, slow release formulations."	( Metoprolol. An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in hypertension, ischaemic heart disease and related cardiovascular disorders. Benfield, P; Brogden, RN; Clissold, SP, 1986)	1.71
" Sixteen patients achieved the target DBP of 90 mmHg measured 12 hours after dosing and only one patient still had a DBP greater than 95 mmHg."	( The effects of combining felodipine and metoprolol in moderate to severe hypertension--a one year study. Chow, J, 1988)	0.54
"Indirect automatic 24-hour blood pressure monitoring has been found to be reliable and valid and thus has been introduced for the evaluation of dosage and efficacy of antihypertensive drugs."	( Follow-up of a method of twenty-four-hour indirect blood pressure monitoring: evaluation of carvedilol, a new antihypertensive agent. Distler, A; Gotzen, R; Meyer-Sabellek, W; Schulte, KL, 1987)	0.27
" Terbutaline in the chosen dosage slightly decreased diastolic blood pressure and did not increase heart rate."	( Beta-adrenoceptor stimulating and blocking agents in essential hypertension: single and combined therapy with terbutaline and metoprolol. Gotzen, R; Meyer-Sabellek, W; Röcker, L; Schulte, KL; Thiede, HM, 1987)	0.48
" It seems probable that the optimal dose of alinidine was not used in this trial and that the dosage could have been higher."	( ST 567 (alinidine) in stable angina: a comparison with metoprolol. Balakumaran, K; Bokslag, M; Fels, PW; Hugenholtz, PG; Jovanovic, A; Lubsen, J; van Es, GA, 1987)	0.52
" A significantly greater effect 24 h after administration was achieved with the CR formulation, when compared with once-daily dosing with metoprolol tablets, 100 mg."	( Pharmacokinetic and pharmacodynamic properties of a new controlled-release formulation of metoprolol: a comparison with conventional tablets. Blomqvist, I; Jonsson, UE; Lundborg, P; Sandberg, A, 1988)	0.7
" The dosage of metoprolol used resulted in mean plasma levels of about 200 nmol/l, which should induce a rapid and sustained degree of beta-blockade."	( Central haemodynamics in acute myocardial infarction. Natural history, relation to enzyme release and effects of metoprolol. Held, P, 1986)	0.83
" and oral dosage regimen of metoprolol early in acute myocardial infarction has been evaluated."	( Metoprolol in acute myocardial infarction. A pharmacokinetic and pharmacodynamic study. Held, PH; Regårdh, CG, 1986)	2.01
" In 8 experiments metoprolol was infused into a fetal vein in increasing dosage (0,04-0,32 mg/min)."	( [Effect of the beta-blocker metoprolol on the cardiovascular system and plasma catecholamines of the fetus in normoxia and acute hypoxia--animal experiment studies]. Kastendieck, E; Martius, J; Paulick, R; Wernze, H, )	0.76
" Dosing was stopped if symptoms warranted or if there was a fall of greater than or equal to 20% in the forced expiratory volume in 1 second."	( Respiratory and cardiac effects of metoprolol and bevantolol in patients with asthma. Ahmad, D; Carruthers, SG; Darke, AC; Parsons, J; Wilcox, PG, 1986)	0.55
" However, the drugs were not equivalent: In addition to its greater potency, nadolol differed from propranolol and metoprolol in the slope of its dose-response curve."	( Comparison of four beta-blockers as assessed by 24-hour ECG recording. Coumel, P; Delhotal-Landes, B; Escoubet, B; Gourmel, B; Leclercq, JF; Maison-Blanche, P; Poirier, JM, 1986)	0.48
" Oral dosing of metoprolol produced no significant changes in reaction time."	( The relationship between serum concentrations and central nervous system actions of metoprolol. Carey, C; Ermer, JC; Gengo, FM; Kalonaros, GC; McHugh, WB, 1985)	0.84
" The plasma concentration-time profiles for both Oros dosage forms were consistent with an extended duration of release and absorption from the gastrointestinal tract."	( Osmotically controlled-delivery of metoprolol in man: in vivo performance of Oros systems with different durations of drug release. Gerardin, A; Godbillon, J; Leroy, D; Moppert, J; Richard, J, 1985)	0.55
"5 h intragastric infusion and a 14/190 Oros controlled-release dosage form, on two separate occasions."	( Influence of site of drug delivery on the systemic availability of metoprolol: comparison of intragastric infusion and 14/190 Oros administration. Barclay, SP; Good, W; John, VA; Shotton, PA; Wardle, HM; Warrington, SJ, 1985)	0.51
"Plasma concentrations and haemodynamic effects at rest and during exercise have been measured in six healthy volunteers after single oral dosing with two Oros drug delivery systems containing 190 mg metoprolol fumarate but with initial release rates of 14 and 19 mg/h, respectively."	( Comparison of single-dose pharmacokinetic and pharmacodynamic properties of two metoprolol Oros systems with different initial zero-order release rates. Barclay, SP; Good, W; John, VA; Shotton, PA; Warrington, SJ, 1985)	0.68
" The results of the first study with a 19 mg/h Oros system indicated that this rate was too rapid to provide the required response under steady-state dosing conditions."	( Oros controlled-release formulations of metoprolol: an approach to the development of a system for once daily administration. Arnold, JD; Good, W; Leeson, LJ; Meeker, JB; Wagner, WE; Zak, SL, 1985)	0.54
"Plasma metoprolol concentrations and haemodynamic effects have been measured in six healthy male volunteers during once daily dosing with a 19/285 Oros system and twice daily dosing with 100 mg conventional tablets, on two separate occasions."	( A multiple dose pharmacokinetic and pharmacodynamic evaluation of conventional and 19/285 Oros formulations of metoprolol in healthy volunteers. Grainger, SL; John, VA; Shotton, PA; Smith, SE, 1985)	0.94
" These results provide some justification for the development of oral dosage forms with extended durations of release even for drugs which undergo significant first-pass metabolism."	( Evaluation of oxprenolol and metoprolol Oros systems in the dog: comparison of in vivo and in vitro drug release, and of drug absorption from duodenal and colonic infusion sites. Fara, JW; Myrback, RE; Swanson, DR, 1985)	0.56
" As a result, after oral dosing the peak plasma concentrations during pregnancy were only 12% to 55% those after delivery, and the plasma AUCs were reduced to the same extent."	( Pregnancy-induced increase in metoprolol metabolism. Högstedt, S; Lindberg, B; Peng, DR; Rane, A; Regårdh, CG, 1985)	0.56
" Blood pressure and heart rate were measured 22 hours after the last tablet of a 2-week dosing period."	( Comparison of the duration of antihypertensive action of atenolol and metoprolol over a 24-hour period. Crowe, PF; Ferguson, RJ, 1985)	0.5
" It is concluded that for the majority of patients metoprolol should be prescribed twice daily when using currently available dosage forms."	( Polymorphic metabolism of metoprolol: clinical studies. Lennard, MS; McGourty, JC; Silas, JH; Tucker, GT; Woods, HF, 1985)	0.82
" Heart rate and contractile force dose-response curves to isoproterenol were equally shifted to the right in a dose-dependent, parallel fashion by constant infusion of ASL-8052."	( Beta-blocking and hemodynamic effects of ASL-8052. Gorczynski, RJ; Hwang, TF; Murthy, VS, )	0.13
" Exercise tests were performed after each dosing period; isoprenaline stimulation was studied at the highest dose level."	( Comparative pharmacodynamics and plasma levels of beta-adrenoceptor blocking drugs. Bodem, G; Gugler, R; Höffgen, K; Krist, R; Raczinski, H, 1980)	0.26
" Metoprolol, a selective beta-1 receptor antagonist, significantly inhibited the glandular enlargement induced by dobutamine or isoproterenol and produced a parallel shift in the isoproterenol dose-response curve."	( Adrenergic beta receptors mediating submandibular salivary gland hypertrophy in the rat. Brenner, GM; Wulf, RG, 1981)	1.17
" 4 The fact that the shift of the dose-response curve of isoprenaline-induced tachycardia was smaller after metoprolol than after propranolol supports the hypothesis that beta 2-adrenoceptors are present in the heart."	( Relevance of selectivity and non-selectivity in beta-adrenoceptor blocking drugs. Bonelli, J, 1982)	0.48
" What remains to be solved is the dosage level."	( Clinical experiences with prenalterol as an antidote to Beta-adrenoceptor blockade. Kulling, P, 1982)	0.26
" After the terbutaline dose-response curve was determined, terbutaline was inhaled three times in increasing doses."	( Pafenolol, a highly selective beta 1-adrenoceptor-antagonist, in asthmatic patients: interaction with terbutaline. Löfdahl, CG; Marlin, GE; Svedmyr, N, 1983)	0.27
" In patients who respond to modest doses of pindolol, twice or even once daily dosing is often adequate."	( Pindolol: a review of its pharmacology, pharmacokinetics, clinical uses, and adverse effects. Golightly, LK, )	0.13
" However, in EM subjects twice-daily dosing is required even if slow release preparations are used, since plasma metoprolol concentrations may remain negligible 24 h after dosing."	( Polymorphic metabolism of beta-adrenoceptor antagonists. Lennard, MS; Ramsay, LE; Silas, JH; Tucker, GT; Woods, HF, 1984)	0.48
" These differences account for many of the observed variations in drug action and dosage scheduling as well as for some of the side effects."	( Beta-adrenergic blockers. Choosing among them. McGoon, MD; Vlietstra, RE, 1984)	0.27
" Bronchial beta-adrenoceptor blockade was assessed as the displacement of the bronchodilator dose-response curve to inhaled isoprenaline after each beta-adrenoceptor blocking drug compared to placebo and expressed as the dose ratio."	( Assessment of beta-adrenoceptor selectivity of a new beta-adrenoceptor antagonist, bisoprolol, in man. Bacon, RJ; Cragg, DJ; Tattersfield, AE, 1984)	0.27
" Three days post-AMI the dose-response curve for isoproterenol of right ventricular dP/dtmax was significantly depressed, while the inotropic effect of histamine was not impaired."	( Impaired beta-adrenergic stimulation in the uninvolved ventricle post-acute myocardial infarction: reversible defect due to excessive circulating catecholamine-induced decline in number and affinity of beta-receptors. Baumann, G; Blömer, H; Blümel, G; Erhardt, WD; Felix, SB; Ludwig, L; Riess, G, 1981)	0.26
" It is concluded that, for similar reductions in heart rate reflecting satisfactory beta-receptor blockade, the antihypertensive effect of metoprolol given at a dosage of 200 mg per day was more rapid in onset after the ordinary tablet formulation but less marked at 12 hours than at 24 hours after the sustained-release formulation."	( A comparative trial of ordinary metoprolol tablets and metoprolol sustained-release tablets in hypertensive patients at rest and on exercise. Kolsky, H; Moisson, P; Witchitz, S, 1984)	0.75
" Simplification of the dosage regimen to once-daily therapy appears to improve the patient's willingness to comply with the physician's instructions."	( A study of efficacy, tolerance and compliance of once-daily versus twice-daily metoprolol (Betaloc) in hypertension. Betaloc Compliance Canadian Cooperative Study Group. Baird, MG; Bentley-Taylor, MM; Carruthers, SG; Dawson, KG; Laplante, LE; Larochelle, P; MacCannell, KL; Marquez-Julio, A; Silverberg, LR; Talbot, P, 1984)	0.5
"The effects of once daily dosage of the two cardioselective beta-adrenoceptor blocking agents, atenolol and metoprolol, were studied in 26 patients with primary hypertension."	( A comparison of 100 mg atenolol and 100 mg metoprolol once a day at rest and during exercise in hypertensives. Atterhög, JH; Castenfors, J; Jorfelt, L; Karlberg, BE; Nilsson, OR; Ohman, KP; Thulin, T; Tolagen, K; Wettre, S, 1984)	0.74
"In a double-blind, cross-over study the effect and tolerance of the non-selective beta-blocker propranolol in a dosage of 80 mg twice daily was compared to that of the beta 1-selective beta-blocker metoprolol 200 mg once daily in Durules (a controlled-release formulation)."	( Metoprolol and propranolol in the prophylactic treatment of classical and common migraine. A double-blind study. Hedman, C; Kangasniemi, P, 1984)	1.9
" The beta 1,2 antagonist employed in the test decreased the contrast dosage by 13 per cent, causing the LD50."	( Diazepam, alpha and beta neurotransmission modifying drugs and contrast media mortality in mice. Johansson, G; Luostarinen, M; Virkkunen, P, 1984)	0.27
" Simultaneous intake of metoprolol and of alcohol in high dosage should be avoided."	( [Effect of metoprolol on the elimination kinetics of ethanol]. Beyer, H; Dittmann, V; Preuss, KJ; Pribilla, O, 1984)	0.96
" The latter, however, was taking antiarrhythmic drugs at a dosage less than that proved to be effective during electropharmacological testing."	( [Value of a serial electropharmacologic study in survivors of a cardiac arrest secondary to ventricular tachycardia or ventricular fibrillation]. Delise, P; Di Pede, F; Piccolo, E; Raviele, A, 1984)	0.27
" Mean reduction in exercise tachycardia at 24 hours after dosing was significantly greater with atenolol and metoprolol SA than with metoprolol SR and conventional metoprolol."	( Duration of beta-blockade with metoprolol and atenolol: influence of drug oxidation. Freestone, S; Lennard, MS; Ramsay, LE; Silas, JH, 1983)	0.76
" Prenalterol dosage was simple and could be guided by blood pressure response."	( Massive metoprolol poisoning treated with prenalterol. Hulting, J; Wallin, CJ, 1983)	0.7
" Propranolol (PROP) in sufficient dosage abolished the chemoreceptor response to NE and also markedly reduced the chemoreceptor response to hypoxia."	( Interaction between norepinephrine and hypoxia on carotid body chemoreception in rabbits. Milsom, WK; Sadig, T, 1983)	0.27
" Co-administration of metoprolol, but not atenolol, increased mean plasma phenprocoumon concentrations 4 and 6 h after dosing and was caused by a decrease in the apparent volume of distribution."	( Pharmacokinetic and pharmacodynamic interactions between phenprocoumon and atenolol or metoprolol. Kirch, W; Kitteringham, NR; Lögering, HJ; Mutschler, E; Ohnhaus, EE; Paar, D; Spahn, H, 1984)	0.8
" Both atenolol and metoprolol lowered resting heart rate and FEV1 significantly and produced a down- and rightward shift of the dose-response curves to infused terbutaline."	( Cardioselectivity of atenolol and metoprolol. A study in asthmatic patients. Löfdahl, CG; Svedmyr, N, 1981)	0.87
"The results of an uncontrolled and open study of a once-a-day dosage of metoprolol (Betaloc) in the management of mild to moderate hypertension are described."	( Metoprolol for hypertension. Open trial in general practice. Fredman, RM, 1982)	1.94
" Long-acting propranolol in a once daily dosage of 160 mg proved to be effective over a 6-week period of treatment with no significant side-effects."	( Comparison of sustained-release clonidine and long-acting propranolol in the treatment of hypertension. Lawson, AA; Rodrigues, E, 1982)	0.26
"Seventeen patients suffering from angina pectoris completed a double-blind trial comparing the efficacy and safety of metoprolol Durules administered once daily and metoprolol tablets administered twice daily both at a daily dosage of 200 mg."	( Treatment of angina pectoris with metoprolol. A comparison between Durules administered once daily and tablets administered twice daily. Orö, L, 1981)	0.75
" and may be preferred by some patients because of the simple dosage regimen."	( Metoprolol in angina pectoris complicated by essential hypertension. A clinical comparison of the antianginal efficacy of metoprolol slow-release tablets (Durules) given once daily and propranolol tablets given twice daily. BLoem, TJ; Lindner, PC, 1981)	1.71
" The once daily dosing schedule may considerably improve patient's compliance."	( A fixed combination of metoprolol slow-release and chlorthalidone, given once daily, in the long-term treatment of arterial hypertension. Bichisao, E; Floris, B; Franchetta, G; Palestini, N; Sonaglioni, G; Verdecchia, P, 1982)	0.57
"The effect of once-daily dosage of the two most widely prescribed cardioselective beta-adrenoceptor antagonists used to treat hypertension--namely, atenolol and metoprolol--was studied in nine carefully selected hypertensive outpatients."	( Atenolol and metoprolol once daily in hypertension. Hawksworth, GM; Lovell, HG; Petrie, JC; Rigby, JW; Scott, AK; Webster, J, 1982)	0.83
" The dosage of each drug was adjusted at monthly clinic visits until satisfactory control of blood pressure was achieved (140/90 mm Hg or less by cuff) or the maximum dose in the study protocol was reached."	( Ambulatory blood pressure during once-daily randomised double-blind administration of atenolol, metoprolol, pindolol, and slow-release propranolol. Floras, JS; Hassan, MO; Jones, JV; Sleight, P, 1982)	0.48
" Each treatment was given for a period of 4 weeks at two different dosage regimens (150 and 300 mg daily for metoprolol, 120 and 240 mg daily for propranolol)."	( Controlled study of metoprolol and propranolol during prolonged administration in patients with essential tremor. Calzetti, S; Findley, LJ; Perucca, E; Richens, A, 1982)	0.8
" After the establishment of these measurements Fenoterol has been given in an increasing dosage up to the upper therapeutical range."	( [The cardiac hazard of tocolysis and antagonising possibilities. I. The haemodynamic situation of the patient during tocolysis/Protection of the myocardium by means of cardioselective beta-blockade. Experimental results (author's transl)]. Heimisch, W; Mendler, N; Schroll, A; Weidenbach, A; Wischnik, A, 1982)	0.26
" We can look forward to newer agents that are efficacious as monotherapy and on a daily or twice daily dosage regimen for the treatment of the vast majority of hypertensive patients."	( Newer antihypertensive agents. Thind, GS, 1980)	0.26
" Patients who responded (diastolic BP less than 95 mmHg) continued on the initial dosage regimen."	( Metoprolol and atenolol administered once daily in primary hypertension. A clinical comparison of the efficacy of two selective beta-adrenoceptor blocking agents. Lyngstam, O; Rydén, L, 1981)	1.71
" After a 2-week period on placebo, patients received either 200 mg slow-release metoprolol once daily or 200 mg conventional metoprolol once daily for 6 weeks before crossing over to the alternative dosage form for a further 6 weeks."	( A double-blind crossover comparative study of the efficacy of single daily doses of conventional and slow-release metoprolol. Harvard, CW; Nievel, JG, 1981)	0.7
"1 A new osmotic pressure mediated delivery system for metoprolol (Lopresor Oros) has been evaluated by measuring the haemodynamic effects and pharmacokinetics after single and multiple oral dosing in young healthy volunteers."	( Comparison of the pharmacodynamic and pharmacokinetic profiles of single and multiple doses of a commercial slow-release metoprolol formulation with a new Oros delivery system. Jack, DB; John, VA; Kendall, MJ; Laugher, SJ; Quarterman, CP; Woods, KL, 1982)	0.72
" These data show that abrupt withdrawal of pindolol after long-term dosing leads to transient cardiac hyperresponsiveness of resting and exercise heart rate at the same time as persistent cardiac hyporesponsiveness to isoproterenol."	( Cardiac hyper- and hyporesponsiveness after pindolol withdrawal. Langlois, S; Rangno, RE; Stewart, J, 1982)	0.26
" The daily dosage of nifedipine during this phase was 10 mg 3 times daily."	( Effects of treatment with nifedipine and metoprolol in essential hypertension. Eggertsen, R; Hansson, L, 1982)	0.53
" 4 In comparison to conventional metoprolol only metoprolol SA was associated with significantly higher plasma metoprolol concentrations at the end of a dosing interval (mean values: conventional, 25 ng/ml, SR 37 ng/ml, SA 51 ng/ml)."	( Comparison of two long-acting preparations of metoprolol with conventional metoprolol and atenolol in healthy men during chronic dosing. Freestone, S; Lennard, MS; Ramsay, LE; Silas, JH, 1982)	0.8
" Concentrations of the pharmacologically active metabolite, H119/66, remain unaltered during chronic dosing of metoprolol."	( The effect of age on the pharmacokinetics of metoprolol and its metabolites. Jack, DB; Kendall, MJ; Quarterman, CP, 1981)	0.73
" There were statistically significant dose-response reductions in systolic and diastolic pressures, heart rate and cardiac output together with a dose-related increase in pulmonary wedge pressure."	( Haemodynamic dose-response effects of i.v. metoprolol in coronary heart disease. Hendry, WG; Silke, B; Taylor, SH, 1981)	0.53
" The flatter dose-response curve of pindolol for exercise heart rate (EHR) has been reported from practolol and oxprenolol, which also exert partial agonist activity."	( Measurement of partial agonist activity of pindolol. Carruthers, SG; Twum-Barima, Y, 1981)	0.26
" This may justify a once daily dosing schedule of the 200 mg dose, aimed at improving patient compliance."	( [Exercise tolerance in angina patients 3 and 24 hours after administration of a new delayed-action preparation of metoprolol]. Bongini, AM; Cordoni, M; Giusti, C; Pentimone, F; Regoli, F; Verdecchia, P, 1981)	0.47
"Pharmacokinetic and pharmacodynamic profiles for metoprolol have been measured in six healthy volunteers after single and multiple dosing with 100 mg conventional formulation twice daily and 200 mg slow-release formulation once daily."	( A single and multiple dose pharmacokinetic and pharmacodynamic comparison of conventional and slow-release metroprolol. John, VA; Kendall, MJ; Quarterman, CP; Welling, PG, 1980)	0.52
"The kinetics and dose-response characteristics of metoprolol were examined in a series of hypertensive patients."	( Metoprolol kinetics and dose response in hypertensive patients. Myers, MG; Thiessen, JJ, 1980)	1.96
" In preliminary studies on three patients the effective dosage for heart rate reduction was determined."	( [Effect of metoprolol on the circulation after head trauma. Studies during continuous intravenous administration (author's transl)]. Fuchs, HJ; Herden, HN; Welter, J, 1980)	0.65
" After a 4-week run-in period when placebo therapy was given, the patients were given oral metoprolol at a starting dosage of 100 mg twice daily."	( A comparison between once-daily and twice-daily administration of metoprolol in the management of hypertension. Chia, BL, 1980)	0.72
" In addition, the findings support the assumption that therapeutic failure with beta-blockers in hyperthyroidism may be due to suboptimal treatment, and that individualized dosage is necessary."	( Effects and plasma levels of propranolol and metoprolol in hyperthyroid patients. Melander, A; Nilsson, OR; Tegler, L, 1980)	0.52
" There were no side-effects related to this cardioselective beta-blocker in the dosage used."	( Intravenous metoprolol and cardiac dysrhythmias. An evaluation in the management of dysrhythmias in outpatient dental anaesthesia. Rollason, WN; Russell, JG, 1980)	0.64
" This finding highlights the need for new treatment strategies that are sufficiently effective throughout the dosing interval, well tolerated, and available in a convenient, once-daily regimen."	( Improving the therapeutic balance between efficacy and tolerability in antihypertensive drugs--the rationale and benefits of combining felodipine and metoprolol. Elmfeldt, D; Trenkwalder, P, 1995)	0.49
" The dose-response curve of isoprenaline/HR was significantly shifted to the right after hypoglycemia."	( Reduced beta-adrenergic sensitivity in healthy volunteers induced by hypoglycemia. Jaeger, R; Jorde, R; Sager, G; Trovik, TS, 1995)	0.29
"Metoprolol Oros tablets were designed to deliver their drug content as a constant rate over a period of time longer than that currently recorded with slow-release dosage forms."	( Stable isotope methodology for studying the performance of metoprolol Oros tablets in comparison to conventional and slow release formulations. Cardot, JM; Godbillon, J; Richard, J, )	1.82
" The variability in plasma concentrations over the dosing interval was found to be markedly less with the felodipine-metoprolol combination than with the combination of nifedipine and atenolol."	( Aiming for steady 24-hour plasma concentrations: a comparison of two calcium antagonist and beta-blocker combinations. Bergstrand, R; Eriksson, M; Lidman, K; Nyberg, G; Olofsson, B, 1993)	0.5
"This study investigated the effects of an osmotic release oral drug delivery system of metoprolol on the changes induced by cumulative doses of inhaled salbutamol on bronchomotor tone, skeletal muscle, and the circulatory system after single (day 1) and multiple (day 7) dosing in 18 hypertensive asthmatic patients (forced expiratory volume in 1 second > 50% predicted; diastolic blood pressure > 90 mm Hg)."	( Osmotic release oral drug delivery system of metoprolol in hypertensive asthmatic patients. Pharmacodynamic effects on beta 2-adrenergic receptors. Bauer, K; Kaik, B; Kaik, G, 1994)	0.77
" After a 4-week placebo run-in period, each beta 1-adrenoceptor blocker was administered at a dosage of 100 mg once daily for 6 weeks."	( Effects of 100 mg of controlled-release metoprolol and 100 mg of atenolol on blood pressure, central nervous system-related symptoms, and general well being. Albrektsen, T; Dimenäs, E; Olofsson, B; Walle, PO; Westergren, G, 1994)	0.56
"A new, once-daily combination tablet containing felodipine and metoprolol has been developed, using extended-release techniques to obtain even plasma concentrations throughout the dosing interval."	( Design and pharmacokinetics of Logimax, a new extended-release combination tablet of felodipine and metoprolol. Abrahamsson, B; Edgar, B; Lidman, K; Wingstrand, K, 1993)	0.74
" After 12 weeks of active treatment, reductions in supine systolic/diastolic blood pressure 24 h after dosing were 20/14, 13/10 and 11/8 mmHg with felodipine-metoprolol, felodipine and metoprolol, respectively."	( Antihypertensive efficacy and tolerability of a new once-daily felodipine-metoprolol combination compared with each component alone. The Swedish/UK Study Group. Dahlöf, B; Hosie, J, 1993)	0.71
" Four subjects withdrew during the randomised phases because of probable drug-related adverse events and six subjects required dosage reductions during the felodipine or combination phases."	( Felodipine, metoprolol and their combination compared with placebo in isolated systolic hypertension in the elderly. Bune, AJ; Chalmers, JP; Russell, AE; Tonkin, AL; West, MJ; Wing, LM, 1994)	0.67
" Pulse rate, blood pressure and dosage of the additional antihypertensive medication as signs of sympathetic disturbance were registered."	( Beta-blockade in acute aneurysmal subarachnoid haemorrhage. Haass, A; Hamann, G; Schimrigk, K, 1993)	0.29
" Before dosing and after placebo, the aortic flow velocity, acceleration and velocity integral increased progressively during exercise, as did heart rate, blood pressure and cardiac output."	( A placebo controlled comparison of the effects of metoprolol and celiprolol on echo-Doppler measurements of cardiovascular function in normal volunteers. Leitch, A; Riddell, JG; Silke, B; Thompson, A, 1995)	0.54
"To discover whether in hypertensives with left ventricular hypertrophy (LVH) the increased muscle mass will completely regress under antihypertensive treatment and drug dosage can in consequence be reduced."	( [Decreasing the antihypertensive dosage during longterm treatment and complete regression of left ventricular hypertrophy]. Behr, U; Franz, IW; Ketelhut, R; Tönnesmann, U, 1996)	0.29
" The drug dosage could either be reduced or the drug completely discontinued in 11 patients (group 1): after 102 +/- 5 months four patients took no drug, while seven were on 100 mg metoprolol."	( [Decreasing the antihypertensive dosage during longterm treatment and complete regression of left ventricular hypertrophy]. Behr, U; Franz, IW; Ketelhut, R; Tönnesmann, U, 1996)	0.49
" In half of them the drug dosage can be reduced or the drug even discontinued."	( [Decreasing the antihypertensive dosage during longterm treatment and complete regression of left ventricular hypertrophy]. Behr, U; Franz, IW; Ketelhut, R; Tönnesmann, U, 1996)	0.29
"The stability of drugs commonly prescribed for use in oral liquid dosage forms but not commercially available as such was studied."	( Stability of labetalol hydrochloride, metoprolol tartrate, verapamil hydrochloride, and spironolactone with hydrochlorothiazide in extemporaneously compounded oral liquids. Allen, LV; Erickson, MA, 1996)	0.57
"Antihypertensive drug combinations have two major advantages: First, dosage of the single components can be reduced, and second, putative side effects can be minimized."	( [Combination antihypertensive therapy in patients with an increased risk profile]. Bartens, W; Nauck, M; Wanner, C, 1996)	0.29
" A dosing algorithm was used to achieve clinically significant beta-adrenergic blockade."	( Beta blockade to prevent atrial dysrhythmias following coronary bypass surgery. Anderson, RP; Guyton, SW; Harvey, E; Holmes, JR; Paull, DL; Tidwell, SL; Woolf, RA, 1997)	0.3
"Metoprolol is not efficacious for the prevention of post-CABG AF even when dosage is titrated to achieve clinical evidence of beta blockade."	( Beta blockade to prevent atrial dysrhythmias following coronary bypass surgery. Anderson, RP; Guyton, SW; Harvey, E; Holmes, JR; Paull, DL; Tidwell, SL; Woolf, RA, 1997)	1.74
") pretreatment with the alpha 1-adrenoceptor antagonist, prazosin, caused the dose-response curve for the effect of gamma 2-MSH on MAP to shift to the right with a decrease in slope, whereas it had no effect on the dose-response curve for the effect on HR."	( Influence of blockade of alpha 1-adrenoceptors, beta 1-adrenoceptors and vasopressin V1A receptors on the cardiovascular effects of gamma 2-melanocyte-stimulating hormone (gamma 2-MSH). De Wildt, DJ; De Winter, TY; Van Bergen, P; Versteeg, DH, 1997)	0.3
" Accordingly, the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF) has been designed to investigate the effect of once-daily dosing of metoprolol succinate controlled release/extended release (CR/XL) when added to standard therapy in patients with CHF."	( Rationale, design, and organization of the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF). The International Steering Committee. , 1997)	0.89
" The possibility of an association between absorption kinetics from dosage forms in humans and Caco-2 monolayer permeability may allow for a direct kinetic interpretation of human oral absorption from Caco-2 monolayer permeability values."	( Human drug absorption kinetics and comparison to Caco-2 monolayer permeabilities. Ginski, MJ; Polli, JE, 1998)	0.3
" The dosage from 50 to 100 mg/day made no difference."	( Preliminary study of the effects of metoprolol and propafenone on ventricular arrhythmia with positive ventricular late potential. Duan, Y; Gao, E; Li, H; Yang, C; Zhou, Y, 1997)	0.57
"This research study was designed to develop model extended-release (ER) matrix tablet formulations for metoprolol tartrate (100 mg) sufficiently sensitive to manufacturing variable and to serve as the scientific basis for regulatory policy development on scale-up and post approval changes for modified-release dosage forms (SUPAC-MR)."	( Development of metoprolol tartrate extended-release matrix tablet formulations for regulatory policy consideration. Augsburger, LL; Hussain, AS; Nellore, RV; Rekhi, GS; Tillman, LG, 1998)	0.87
" After ICD implantation, 70 patients were randomly assigned to treatment with either metoprolol (mean dosage 104+/-37 mg/day in 35 patients) or d,l-sotalol (mean dosage 242+/-109 mg/day in 35 patients)."	( Comparison of metoprolol and sotalol in preventing ventricular tachyarrhythmias after the implantation of a cardioverter/defibrillator. Hauer, B; Schwick, NG; Seidl, K; Senges, J; Zahn, R, 1998)	0.88
"While the analysis of in vitro dissolution-in vivo absorption relationships from oral solid dosage forms provides biopharmaceutical insight and regulatory benefit, no well developed method exists to predict dissolution-absorption relationships a priori to human studies."	( Prediction of dissolution-absorption relationships from a dissolution/Caco-2 system. Ginski, MJ; Polli, JE, 1999)	0.3
"The objective of this study, was to examine the influence of critical formulation and processing variables as described in the AAPS/FDA Workshop II report on scale-up of oral extended-release dosage forms, using a hydrophilic polymer hydroxypropyl methylcellulose (Methocel K100LV)."	( Identification of critical formulation and processing variables for metoprolol tartrate extended-release (ER) matrix tablets. Augsburger, LL; Hussain, AS; Malinowski, HJ; Nellore, RV; Rekhi, GS; Tillman, LG, 1999)	0.54
"Thirty consecutive DCM patients with persistent LV dysfunction (ejection fraction < or =40%) and reduced exercise tolerance (peak oxygen consumption <25 ml/kg/min) despite chronic (>1 year) tailored treatment with metoprolol and angiotensin-converting enzyme inhibitors were enrolled in a 12-month, open-label, parallel trial and were randomized either to continue on metoprolol (n = 16, mean dosage 142+/-44 mg/day) or to cross over to maximum tolerated dosage of carvedilol (n = 14, mean dosage 74+/-23 mg/day)."	( Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol. The Heart-Muscle Disease Study Group. Camerini, F; Ciani, F; Di Lenarda, A; Gregori, D; Klugmann, S; Mestroni, L; Muzzi, A; Pinamonti, B; Sabbadini, G; Salvatore, L; Sinagra, G, 1999)	0.69
" Metoprolol 25 mg capsules were used as a control oral dosage form."	( The relative bioavailability of metoprolol following oral and rectal administration to volunteers and patients. Beysens, AJ; de Stoppelaar, FM; Gorgels, AP; Stappers, JL; Stolk, LM, 1999)	1.5
"5 mg once per day (NYHA class III or IV), titrated for 6 to 8 weeks up to a target dosage of 200 mg once per day (n = 1990); or matching placebo (n = 2001)."	( Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group. Aldershvile, J; Ball, S; Deedwania, P; Dietz, R; Dunselman, PH; El Allaf, D; Fagerberg, B; Goldstein, S; Gottlieb, S; Gullestad, L; Halinen, M; Herlitz, J; Hjalmarson, A; Jánosi, A; Kjekshus, J; Kuch, J; Neuhaus, KL; Rickenbacher, P; Thorgeirsson, G; Vítovec, J; Waagstein, F; Wedel, H; Wikstrand, J, 2000)	0.6
" In one study that titrated dosages to effect, fewer felodipine/metoprolol than felodipine or metoprolol monotherapy recipients required dosage increases to achieve BP control (45 vs 60 and 67%, respectively)."	( Felodipine/metoprolol: a review of the fixed dose controlled release formulation in the management of essential hypertension. Haria, M; Markham, A; Plosker, GL, 2000)	0.94
" It has been applied to the determination of (R)-(+)-metoprolol and (S)-(-)-metoprolol in urine from healthy volunteers dosed with racemic metoprolol tartrate."	( Determination of metoprolol enantiomers in human urine by coupled achiral-chiral chromatography. Kang, JS; Kim, HJ; Kim, KH; Mar, W, 2000)	0.9
" Liver blood flow through individual hepatic vessels was measured up to 8 hours after dosage administration using a duplex Doppler ultrasound technique."	( Effect of metoprolol and verapamil administered separately and concurrently after single doses on liver blood flow and drug disposition. Bauer, LA; Easterling, TR; Horn, JR; Maxon, MS; Shen, DD; Strandness, DE, 2000)	0.71
" The study medication was titrated over 6 weeks, the mean final dosage was 135 mg/day."	( MIC trial: metoprolol in patients with mild to moderate heart failure: effects on ventricular function and cardiopulmonary exercise testing. Böhm, M; Darius, H; Genth-Zotz, S; Hanrath, P; Hartmann, D; Meyer, J; Sigmund, M; Treese, N; Waagstein, F; Zotz, RJ, 2000)	0.7
" The enantiomeric disposition of MET is reported following racemic administration as a single and as multiple oral dosing four times per day for four days in male Sprague-Dawley rats (n=6 in each group)."	( Pharmacokinetics of metoprolol enantiomers following single and multiple administration of racemate in rat. Foster, RT; Mostafavi, SA, 2000)	0.63
"The MERIT-HF study was designed to investigate the effect of once-daily dosing of metoprolol succinate CR/XL added to standard therapy in patients with chronic heart failure."	( Screening, endpoint classification, and safety monitoring in the Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Fagerberg, B, 2000)	0.77
" Treatment with metoprolol CR/XL was initiated at a low dosage of 12."	( Metoprolol: a review of its use in chronic heart failure. Markham, A; Prakash, A, 2000)	2.1
" It is also necessary to define the initiation and increase of dosage and the target dose of the beta-blocker."	( [Beta-blockers in the treatment of chronic heart failure. How should results of clinical studies be introduced into clinical practice]. Spinar, J; Vítovec, J, 2000)	0.31
" Metoprolol was dosed to achieve a resting predobutamine heart rate below 65 beats/minute or a total intravenous dose of 20 mg."	( Effect of intravenous metoprolol or intravenous metoprolol plus glucagon on dobutamine-induced myocardial ischemia. Ahlberg, AW; Heller, GV; Katten, D; Murthy, DR; Salloum, A; White, CM, 2000)	1.53
" Therefore, it is quite possible that both drugs produce adverse immunological effects in vivo in cases of high dosage or obstruction of elimination."	( [Effect of migraine medications on monocyte chemotaxis] . Krumholz, W; Menges, T; Ogal, H; Szalay, G, 2000)	0.31
"The results suggest that once-daily dosing with either the free or fixed combination of felodipine 5 mg and metoprolol 50 mg produces a significant sustained reduction in systolic and diastolic BP with similar plasma concentration profiles over a 24-h period."	( The pharmacodynamic and pharmacokinetic profiles of controlled-release formulations of felodipine and metoprolol in free and fixed combinations in elderly hypertensive patients. Elliott, HL; Hosie, J; MacDonald, TM; McLay, JS, 2000)	0.73
" Taking the half-life of metoprolol into account this yields an even plasma concentration over 24 hours with a once daily dosage scheme."	( Achieving optimal beta1-blockade with metoprolol CR/Zok. Wikstrand, J, 2000)	0.88
" This dosage regimen could be modified according to the judgement of the investigator."	( MERIT-HF--description of the trial. Wikstrand, J, 2000)	0.31
" A thorough patient evaluation should be performed to determine optimal dosage and titration of this drug, as with any beta-blocker, and to assess the potential for drug-drug or drug-disease interactions."	( Metoprolol CR/XL in the treatment of chronic heart failure. Gattis, WA, 2001)	1.75
", dosing rate or enantiomer-enantiomer interaction) or the patient (e."	( Stereospecific pharmacokinetics and pharmacodynamics of beta-adrenergic blockers in humans. Brocks, DR; Mehvar, R, )	0.13
" Patients who could not be dosed with up to 40 mg daily of metoprolol or 20 mg daily of carvedilol were defined as intolerant."	( Comparative left ventricular functional and neurohumoral effects of chronic treatment with carvedilol versus metoprolol in patients with dilated cardiomyopathy. Hanatani, A; Hirooka, K; Hori, M; Ishida, Y; Komamura, K; Miyatake, K; Nakatani, S; Yamagishi, M; Yasumura, Y, 2001)	0.77
" These results suggest a dissolution/Caco-2 system to be an experimentally based tool that may predict dissolution-absorption relationships from oral solid dosage forms, and hence the relative contributions of dissolution and permeation to oral drug absorption kinetics."	( Prediction of dissolution-absorption relationships from a continuous dissolution/Caco-2 system. Ginski, MJ; Polli, JE; Taneja, R, 1999)	0.3
" It is suggested that patients can safely be switched from multiple dosing of metoprolol IR 50 mg to a once-daily dose of metoprolol CR/XL."	( Dose-related effects of metoprolol on heart rate and pharmacokinetics in heart failure. Aberg, J; Andersson, B; Lindelöw, B; Täng, MS; Wikstrand, J, 2001)	0.85
" There was no change in diuretic or ACE inhibitor dosing with beta-blocker titration."	( Tolerability of beta-blocker initiation and titration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF). Deedwania, P; Fisher, ML; Gottlieb, SS; Gullestad, L; Kjekshus, J; Vitovec, J; Wikstrand, J, 2002)	0.56
" Pharmacopeia (USP) apparatus 3 can be used as an alternative to USP apparatus 2 for dissolution testing of immediate-release (IR) dosage forms."	( Evaluation of USP apparatus 3 for dissolution testing of immediate-release products. Hussain, AS; Wang, JT; Yu, LX, 2002)	0.31
"We performed a post-hoc subgroup analysis in the Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) with the aim of reporting on the heart rate (HR) response during the titration phase and clinical outcomes from the three-month follow-up visit to end of study in two dosage subgroups: one that had reached more than 100 mg of metoprolol CR/XL once daily (high-dose group; n = 1,202; mean 192 mg) and one that had reached 100 mg or less (low-dose group; n = 412; mean 76 mg)."	( Dose of metoprolol CR/XL and clinical outcomes in patients with heart failure: analysis of the experience in metoprolol CR/XL randomized intervention trial in chronic heart failure (MERIT-HF). Fagerberg, B; Goldstein, S; Hjalmarson, A; Kjekshus, J; Waagstein, F; Wedel, H; Wikstrand, J, 2002)	1
" Once-daily dosing of ER metoprolol succinate 12."	( Pharmacokinetic considerations of formulation: extended-release metoprolol succinate in the treatment of heart failure. Andersson, B; Kendall, MJ; Klibaner, M; Stanbrook, H; Wikstrand, J, 2003)	0.86
" All centres were provided with carvedilol, metoprolol, and bisoprolol at appropriate doses; the choice of the drug and dosage was left to the responsible clinician."	( Treatment of chronic heart failure with beta adrenergic blockade beyond controlled clinical trials: the BRING-UP experience. Balli, E; Geraci, E; Gorini, M; Gronda, E; Lucci, D; Maggioni, AP; Opasich, C; Sinagra, G; Tavazzi, L; Tognoni, G, 2003)	0.58
" Starting treatment with beta blockers did not affect the prescription or dosage of other recommended drugs."	( Treatment of chronic heart failure with beta adrenergic blockade beyond controlled clinical trials: the BRING-UP experience. Balli, E; Geraci, E; Gorini, M; Gronda, E; Lucci, D; Maggioni, AP; Opasich, C; Sinagra, G; Tavazzi, L; Tognoni, G, 2003)	0.32
"ER metoprolol succinate is a controlled-release tablet designed to produce even and consistent beta(1)-blockade throughout the 24-hour dosing interval, with less fluctuation in metoprolol plasma concentrations compared with immediate-release metoprolol."	( Extended-release metoprolol succinate in chronic heart failure. Patterson, JH; Tangeman, HJ, 2003)	1.28
" ER metoprolol succinate is administered once daily, is well tolerated, and provides consistent beta(1)-blockade over the 24-hour dosing interval."	( Extended-release metoprolol succinate in chronic heart failure. Patterson, JH; Tangeman, HJ, 2003)	1.22
" However, nicardipine did not alter the R/S metoprolol ratio in plasma 3 h after dosing, the plasma concentration of S-(-)-metoprolol 3 h after dosing or the beta-adrenoceptor blockade produced by metoprolol in subjects of both phenotypes."	( Influence of CYP2D6-dependent metabolism on the steady-state pharmacokinetics and pharmacodynamics of metoprolol and nicardipine, alone and in combination. Decolin, D; Funck-Brentano, C; Jaillon, P; Laurent-Kenesi, MA; Poirier, JM, 1993)	0.76
" All of the subjects were given 25, 50, or 75 mg of metoprolol every 8 hours; the dosages were given in a random order, and each dosage was given for 1 day."	( Gly389Arg polymorphism of beta1-adrenergic receptor is associated with the cardiovascular response to metoprolol. Chen, XP; Liu, J; Liu, ZQ; Tan, ZR; Wang, LS; Zhou, G; Zhou, HH, 2003)	0.78
"Intravenous dosing was initially done via jugular cannula."	( Iontophoretic in vivo transdermal delivery of beta-blockers in hairless rats and reduced skin irritation by liposomal formulation. Banga, AK; Betageri, GV; Chaturvedula, A; Conjeevaram, R; Sunkara, G, 2003)	0.32
" Pharmacokinetic and pharmacodynamic analyses, however, indicate that the dosing regimen of metoprolol selected for use in the COMET trial produces a magnitude and time course of beta(1)-blockade during a 24-hour period that is similar to the dose of carvedilol targeted for use in the trial."	( Do beta-blockers prolong survival in heart failure only by inhibiting the beta1-receptor? A perspective on the results of the COMET trial. Packer, M, 2003)	0.54
" We analyze the problems with the trial design of COMET from the standpoint of comparing 2 therapeutic agents at different positions on a common dose-response curve, and discuss the theoretical reasons why postjunctional adrenergic receptor blockade that is in addition to beta1-receptor antagonism will likely produce only minimal or no incremental benefit in chronic heart failure."	( Selective versus nonselective beta-blockade for heart failure therapy: are there lessons to be learned from the COMET trial? Adams, KF; Bristow, MR; Feldman, AM; Goldstein, S, 2003)	0.32
" These include the choice of dose and dosage regimen of immediate-release metoprolol tartrate, a dosage form that has never been shown to reduce mortality in patients with heart failure."	( Pharmacodynamics of beta-blockers in heart failure: lessons from the carvedilol or metoprolol European trial. Bauman, JL; Talbert, RL, 2004)	0.78
" The delayed T(max) lower C(max) decreased K(a) unaltered bioavailability and prolonged t(1/2) indicated a slow and prolonged release of metoprolol tartrate from guar gum three-layer matrix tablets in comparison with the immediate release tablet dosage form."	( Pharmacokinetic evaluation of guar gum-based three-layer matrix tablets for oral controlled delivery of highly soluble metoprolol tartrate as a model drug. Al-Saidan, SM; Bhaskar, P; Karthikeyan, RS; Krishnaiah, YS; Satyanarayana, V, 2004)	0.73
" Results from the recently published trials are summarized to emphasize the proper selection and dosage of beta blocker therapy to optimize the care of this high risk population."	( The effects of beta blockers on morbidity and mortality in heart failure. Jafri, SM, 2004)	0.32
" Furthermore, the dosing of metoprolol tartrate in COMET may have been inadequate based on prior studies."	( Pharmacokinetics and pharmacodynamics of beta blockers in heart failure. Talbert, RL, 2004)	0.62
"Data from electronic dosing monitors and published pharmacokinetic parameters were used to derive medication adherence measures for immediate-release metoprolol and examine their association with health care utilization of outpatients aged 50 years or older with heart failure."	( Association between adherence measurements of metoprolol and health care utilization in older patients with heart failure. Brater, DC; Li, J; Morris, AB; Murray, MD; Tu, W; Wu, J; Young, J, 2005)	0.79
" Projected mean plasma concentrations (Cp(ave)) were estimated by use of data from recorded dosing times."	( Association between adherence measurements of metoprolol and health care utilization in older patients with heart failure. Brater, DC; Li, J; Morris, AB; Murray, MD; Tu, W; Wu, J; Young, J, 2005)	0.59
" The dosage forms were administered to four dogs and the plasma levels were measured using LC-MS/MS."	( Pharmacokinetics of an immediate release, a controlled release and a two pulse dosage form in dogs. Amidon, GL; Kim, JS; Löbenberg, R, 2005)	0.33
" The relative bioavailability of two FDA approved (Orange Book AB rating) solid oral dosage forms of metoprolol and propranolol/hydrochlorothiazide (combination tablets) was evaluated in human volunteers under fed conditions using a two-way crossover design."	( The effect of food on the relative bioavailability of rapidly dissolving immediate-release solid oral products containing highly soluble drugs. Asafu-Adjaye, E; Ciavarella, AB; Conner, DP; Faustino, PJ; Hussain, AS; Lesko, LJ; Mehta, MU; Parekh, A; Straughn, AB; Yang, Y; Yu, LX, )	0.35
"The Carvedilol or Metoprolol European Trial (COMET) compared the effects of a comprehensive adrenergic antagonist, carvedilol (target dosage 25 mg twice daily), with a beta-1-selective agent, metoprolol tartrate (target dosage 50 mg twice daily), in 3029 patients with chronic heart failure caused by left ventricular systolic dysfunction."	( Comprehensive adrenergic receptor blockade with carvedilol is superior to beta-1-selective blockade with metoprolol in patients with heart failure: COMET. Cleland, JG, 2004)	0.87
" If blood pressure was above normal on the 15th day of follow-up, the metoprolol dosage was doubled."	( Beta blocker effects on plasma homocysteine levels in patients with hypertension. Atar, I; Atar, IA; Aydinalp, A; Bozbaş, H; Demircan, S; Korkmaz, ME; Müderrisoğlu, H; Ozin, B; Yildirir, A, 2005)	0.56
" Therefore we analyzed 24-h ECG Holter recordings from a study which compared the long-term clinical efficacy of metoprolol tartrate to carvedilol in chronic heart failure patients using the same dosing regimen as in COMET."	( Do metoprolol and carvedilol have equivalent effects on diurnal heart rate in patients with chronic heart failure? Chan, SK; Fung, JW; Leung, LY; Sanderson, JE; Yip, GW; Yu, CM, 2005)	1.16
" Exposure to gefitinib is increased by coadministration with CYP3A4 inhibitors, but since gefitinib is known to have a good tolerability profile, a dosage reduction is not recommended."	( Pharmacokinetic drug interactions of gefitinib with rifampicin, itraconazole and metoprolol. Laight, A; Leadbetter, J; McKillop, D; Ranson, M; Smith, RP; Swaisland, HC; Wild, MJ, 2005)	0.55
" The dosage of metoprolol was determined on an individual basis and could be freely adjusted on clinical grounds."	( Impact of CYP2D6 genotype on adverse effects during treatment with metoprolol: a prospective clinical study. Delabar, U; Eichelbaum, M; Fux, R; Gleiter, CH; Kivistö, KT; Lorenz, G; Mörike, K; Pröhmer, AM; Schaeffeler, E; Schwab, M, 2005)	0.92
"Our data suggest that pharmacogenetic measures could be used to design a more individualized metoprolol dosage regimen for patients."	( The relevance of CYP2D6 genetic polymorphism on chronic metoprolol therapy in cardiovascular patients. Ismail, R; Teh, LK, 2006)	0.8
" Dosage of metoprolol was adjusted according to heart rate."	( Intravenous administration of metoprolol is more effective than oral administration in the prevention of atrial fibrillation after cardiac surgery. Auvinen, T; Hakala, T; Halonen, J; Halonen, P; Hartikainen, J; Hippeläinen, M; Karjalainen, J; Turpeinen, A; Uusaro, A, 2006)	1.01
" In males, NEB at either dosing time decreased HR and BP to a greater extent than did MET."	( Gender dependency of circadian blood pressure and heart rate profiles in spontaneously hypertensive rats: effects of beta-blockers. Grundt, C; Lemmer, B; Meier, K, 2006)	0.33
" All patients received metoprolol at a dosage titrated to achieve a diastolic blood pressure below 90 mm Hg."	( Discordant beta-blocker effects on clinic, ambulatory, resting, and exercise hemodynamics in patients with hypertension. Beitelshees, AL; Johnson, JA; Pauly, DF; Yarandi, HN; Zineh, I, 2006)	0.64
" Based on this knowledge, the effects of the films' composition and thickness on the resulting drug release kinetics (also from coated solid dosage forms) can be predicted in a quantitative way."	( Drugs acting as plasticizers in polymeric systems: a quantitative treatment. Le Brun, V; Siepmann, F; Siepmann, J, 2006)	0.33
"The FDA has published recommendations for sponsors who wish to request a waiver of in vivo bioavailability (BA) or bioequivalence (BE) studies for immediate release (IR) solid oral dosage forms based on the Biopharmaceutics Classification System (BCS)."	( The suitability of an in situ perfusion model for permeability determinations: utility for BCS class I biowaiver requests. Amidon, GL; Hilfinger, J; Kijek, P; Kim, JS; Mitchell, S; Tsume, Y, )	0.13
" Based on this evidence, it is now recommended to add beta-blockers such as metoprolol CR/XL with an escalating dosage regimen to the treatment of patients with symptomatic heart failure who already are receiving a stable medical regimen including angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, diuretics, vasodilators, or digitalis."	( The use of metoprolol CR/XL in the treatment of patients with diabetes and chronic heart failure. De Freitas, O; Fornoni, A; Lenz, O; Materson, BJ, 2006)	0.95
"The present study investigates if drug diffusion through plasticized isolated ethylcellulose (EC)/hydroxypropyl methylcellulose (HPMC) films prepared by solvent casting can be used as a tool to develop spray-coated dosage forms."	( Correlation between the permeability of metoprolol tartrate through plasticized isolated ethylcellulose/hydroxypropyl methylcellulose films and drug release from reservoir pellets. Remon, JP; Rombout, P; Van den Mooter, G; Vervaet, C; Ye, ZW, 2007)	0.61
"Infusion dosage and timing, vital signs and adverse events."	( Safety of a postoperative beta-blocker infusion protocol for nonmonitored units in a community hospital. Atlas, S; Drury, J; Zarraga, I, 2007)	0.34
" The maximum volume of drug solution absorbed was limited (2x100 microl), revealing that these porous carriers were ideal for low dosed formulations."	( Porous hydroxyapatite tablets as carriers for low-dosed drugs. Cnudde, V; Cosijns, A; Luyten, J; Masschaele, B; Mullens, S; Remon, JP; Siepmann, F; Van Hoorebeke, L; Vervaet, C, 2007)	0.34
" Beta-blocker dosages were titrated, and three patients achieved the target beta-blocker dosage established for stage A-C heart failure."	( Tolerability of beta-blockers in outpatients with refractory heart failure who were receiving continuous milrinone. Earl, GL; Fitzpatrick, JM; Narula, J; Verbos-Kazanas, MA, 2007)	0.34
"5 mg/day, with the dosage titrated to 25 mg/day if tolerated."	( Association of beta-blocker dose with serum procollagen concentrations and cardiac response to spironolactone in patients with heart failure. Camp, JR; Cavallari, LH; Groo, VL; Momary, KM; Stamos, TD; Viana, MA, 2007)	0.34
"A randomized, controlled trial was conducted in an outpatient setting to examine the effect of beta-blocker dosing frequency on patient compliance, clinical outcome, and health-related quality of life in patients with stable angina pectoris."	( Compliance, clinical outcome, and quality of life of patients with stable angina pectoris receiving once-daily betaxolol versus twice daily metoprolol: a randomized controlled trial. Kardas, P, 2007)	0.54
"4% for those with a reduced dosage (n."	( Should beta-blocker therapy be reduced or withdrawn after an episode of decompensated heart failure? Results from COMET. Cleland, JG; Dei Cas, L; Di Lenarda, A; Komajda, M; Metra, M; Poole-Wilson, PA; Remme, WJ; Spark, P; Swedberg, K; Torp-Pedersen, C, 2007)	0.34
"The aim of this work was to study the possibility to obtain an oral extended-release dosage forms with zero order kinetic release by coating minitablets (containing metoprolol tartrate) with insoluble methacrylate film coating (Eudragit NE 40D) in a fluidized bed system."	( The influence of formulation factors on the kinetic release of metoprolol tartrate from prolong release coated minitablets. Leucuta, SE; Tomuta, I, 2007)	0.77
" As comparisons to metoprolol succinate as well as to optimally dosed metoprolol tartrate are missing, a definite superiority of carvedilol cannot be assumed."	( [Beta-adrenoceptor antagonists and ACE-inhibitors. Carvedilol compared with metoprolol as combination partner in cases of diabetes and hypertension]. Frese, T; Sandholzer, H, 2007)	0.9
" In period II, the volunteers received the other dosage form."	( Comparative bioavailability of metoprolol tartrate after oral and transdermal administration in healthy male volunteers. Ali, A; Aqil, M; Saha, N; Sultana, Y, 2007)	0.63
"A simple, precise, specific and accurate reverse phase HPLC method has been developed for the simultaneous determination of metoprolol succinate (MS) and amlodipine besylate (AB) in tablet dosage form."	( Simultaneous determination of metoprolol succinate and amlodipine besylate in pharmaceutical dosage form by HPLC. Dongre, VG; Jadhav, VK; Karmuse, PP; Phadke, M; Shah, SB, 2008)	0.84
"Atenolol and metoprolol succinate, dosed once daily, have different pharmacokinetic profiles."	( Comparative efficacy of two different beta-blockers on 24-hour blood pressure control. Bakris, GL; Basta, E; Bogojevic, Z; Kirstner, E; Sarafidis, P, 2008)	0.72
" Accordingly, the authors have investigated dosing equivalency by examining baseline and peak exercise heart rates and norepinephrine levels in subjects with chronic heart failure treated with carvedilol or metoprolol."	( Differential effects of carvedilol and metoprolol succinate on plasma norepinephrine release and peak exercise heart rate in subjects with chronic heart failure. Ahuja, K; Hirsh, DS; Jorde, UP; Kasper, ME; Khandwalla, RM; Tseng, CH; Vittorio, TJ; Zolty, R, 2008)	0.8
" Salicylic acid, caffeine and metoprolol were individually dosed to the ligated stomach."	( The development of multiple probe microdialysis sampling in the stomach. Lunte, CE; Woo, KL, 2008)	0.63
" To assess the significance of this multiple probe approach, drug concentrations in each probe location were monitored after selected compounds were dosed to the ligated stomach by oral gavage."	( The direct comparison of health and ulcerated stomach tissue: a multiple probe microdialysis sampling approach. Lunte, CE; Woo, KL, 2008)	0.35
" The dosage of metoprolol was adjusted according to the blood pressure and heart rate."	( [Effects of metoprolol on perioperative cardiovascular events in patients with risk or at high risk for coronary artery disease undergoing non-cardiac surgery]. Wang, Q; Wang, S; Wu, XM; Yang, XY, 2008)	1.08
"Simple, accurate, economical, and reproducible UV spectrophotometric and column high-performance liquid chromatographic (HPLC) methods were developed for simultaneous estimation of a 2-component drug mixture of metoprolol tartrate and hydrochlorothiazide in combined tablet dosage form."	( Spectrophotometric and column high-performance liquid chromatographic methods for simultaneous estimation of metoprolol tartrate and hydrochlorothiazide in tablets. Garg, G; Saraf, S, )	0.53
" In the first 60 to 90 days after hospital discharge, little up-titration in beta-blocker dosing occurs."	( Dosing of beta-blocker therapy before, during, and after hospitalization for heart failure (from Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure). Abraham, WT; Albert, NM; Fonarow, GC; Gheorghiade, M; Greenberg, BH; O'Connor, CM; Stough, WG; Sun, JL; Yancy, CW; Young, JB, 2008)	0.35
" Dosage should be lower and administration should be implemented longer before the operation."	( [Perioperative beta-blockade for reduction of cardiovascular complications in non-cardiac surgery: advantages and disadvantages]. Koelemay, MJ; Legemate, DA, 2008)	0.35
"Multiparticulate drug delivery systems, such as pellets, are frequently used as they offer therapeutic advantages over single-unit dosage forms."	( Porous pellets as drug delivery system. Cosijns, A; De Beer, T; Evrard, B; Nikolakakis, I; Nizet, D; Remon, JP; Siepmann, F; Siepmann, J; Vervaet, C, 2009)	0.35
" The obtained new insight into the occurring drug-polymer interactions can help to facilitate the development/optimisation of this type of dosage forms."	( Characterisation of quaternary polymethacrylate films containing tartaric acid, metoprolol free base or metoprolol tartrate. Glaessl, B; Rades, T; Siepmann, F; Siepmann, J; Tucker, I, 2009)	0.58
" By contrast, the totally administered dosage of epinephrine correlated with NTRM in males (r=0."	( A beta-adrenergic antagonist reduces traumatic memories and PTSD symptoms in female but not in male patients after cardiac surgery. Grathwohl, M; Hauer, D; Kaufmann, I; Krauseneck, T; Padberg, F; Roozendaal, B; Schelling, G; Schmoeckel, M; Weis, F, 2010)	0.36
" Admission daily doses of metoprolol averaged 58 mg compared to discharge daily doses of 88 mg; only 52% of patients had dosage increases."	( Use of beta-blockers and effects on heart rate and blood pressure post-acute coronary syndromes: are we on target? Donovan, J; Goldberg, RJ; Gore, JM; Herman, M; McKenna, B; Tighe, DA; Tran, M, 2009)	0.65
" The obtained new insight into the underlying drug release mechanisms in Eudragit RL networks can help to facilitate the optimisation of this type of dosage forms."	( Deeper insight into the drug release mechanisms in Eudragit RL-based delivery systems. Glaessl, B; Rades, T; Siepmann, F; Siepmann, J; Tucker, I, 2010)	0.36
"Studies have demonstrated an influence of dosage release formulations on drug interactions and enantiomeric plasma concentrations."	( Influence of metoprolol dosage release formulation on the pharmacokinetic drug interaction with paroxetine. Bleske, BE; Brook, R; Kerber, K; Nielsen, J; Shea, M; Stout, SM; Welage, LS, 2011)	0.74
"The Biopharmaceutical Classification System (BCS) guidance issued by the FDA allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release (IR) solid oral dosage forms only for BCS class I drugs."	( The biowaiver extension for BCS class III drugs: the effect of dissolution rate on the bioequivalence of BCS class III immediate-release drugs predicted by computer simulation. Amidon, GL; Tsume, Y, 2010)	0.36
" The design of dosage form was performed by choosing hydrophilic hydroxypropyl methyl cellulose (HPMC K100M) and hydrophobic ethyl cellulose (EC) polymers as matrix builders and Eudragit® RL/RS as coating polymers."	( Development of sustained release capsules containing "coated matrix granules of metoprolol tartrate". Bigoniya, P; Khanam, J; Siddique, S, 2010)	0.59
" Each pellet acts as a separate drug delivery unit and is designed to deliver metoprolol continuously over the dosage interval."	( Tablet splitting: Product quality assessment of metoprolol succinate extended release tablets. Khan, M; Sayeed, VA; Tawakkul, M; Zhao, N; Zidan, A, 2010)	0.84
" Change to a weekly dosage schedule with slow infusions has been tested, a strategy that requires more frequent hospital visits and increased storage resources[7,9]."	( Cardioprotective effect of metoprolol and enalapril in doxorubicin-treated lymphoma patients: a prospective, parallel-group, randomized, controlled study with 36-month follow-up. Ahimastos, A; Anagnostopoulos, N; Galanopoulos, A; Georgakopoulos, P; Georgiakodis, F; Karavidas, A; Kyriakidis, M; Marinakis, T; Matsakas, E; Roussou, P; Zimeras, S, 2010)	0.66
" The dosage of the drugs was unknown."	( Distribution of metoprolol, tramadol, and midazolam in human autopsy material. Arenz, N; Goltz, L; Kirch, W; Oertel, R; Pietsch, J; Zeitz, SG, 2011)	0.72
" The delayed T(max) and lower C(max) indicated a slow and SR of MS from the optimized matrix tablets in comparison with the immediate release dosage form."	( Modulation of drug (metoprolol succinate) release by inclusion of hydrophobic polymer in hydrophilic matrix. Bose, A; Khanam, J; Siddique, S, 2011)	0.69
" In all cases the dosage of the drug was unknown."	( Distribution of metoprolol in human autopsy material. Arenz, N; Goltz, L; Kirch, W; Oertel, R; Pietsch, J, 2011)	0.72
"We hypothesized that uptitration of β blockade and adjustment of pacing parameters to achieve a prevalence of single chamber atrial inhibited rate-responsive (AAIR) pacing in patients with dual-chamber implantable cardioverter--defibrillators (ICDs) would result in maximization of β-blocker dosage and thus decrease appropriate ICD therapies."	( Relation of ventricular tachycardia/fibrillation to beta-blocker dose maximization guided by pacing mode analysis in nonpacemaker-dependent patients with implantable cardioverter-defibrillator. Deftereos, S; Giannopoulos, G; Kaoukis, A; Kossyvakis, C; Manolis, AS; Ntzouvara, O; Panagopoulou, V; Perpinia, A; Pyrgakis, V; Raisakis, K; Rentoukas, I; Stefanadis, C, 2011)	0.37
" We proposed a systematic classification scheme using FDA-approved drug labeling to assess the DILI potential of drugs, which yielded a benchmark dataset with 287 drugs representing a wide range of therapeutic categories and daily dosage amounts."	( FDA-approved drug labeling for the study of drug-induced liver injury. Chen, M; Fang, H; Liu, Z; Shi, Q; Tong, W; Vijay, V, 2011)	0.37
" The in vitro dissolution study showed pH dependent release profiles suggesting that the PCP NPs system have great potential for oral controlled drug delivery as an alternative to conventional dosage forms."	( Preparation and optimization of PMAA-chitosan-PEG nanoparticles for oral drug delivery. Boateng, JS; Douroumis, D; Pawar, H, 2012)	0.38
"To explore the effectiveness of the metoprolol dosage adjustment on reducing the incidence of electrical-storm (ES) in patients with Implantable Cardioverter Defibrillators (ICDs)."	( [Impact of metoprolol use in the treatment of patients with electrical-storm after cardioverter defibrillators implantation]. Cao, KJ; Chen, C; Chen, ML; Hou, XF; Li, WQ; Shan, QJ; Xu, DJ; Yang, B; Yu, JB; Zhang, FX; Zhang, R; Zou, JG, 2011)	1.03
" In the chronic phase, 2 patients with Brugada syndrome were treated with Quinidine mono-therapy while the dosage of metoprolol was adjusted in the remaining 23 patients and the dosage of metoprolol was increased gradually from (26."	( [Impact of metoprolol use in the treatment of patients with electrical-storm after cardioverter defibrillators implantation]. Cao, KJ; Chen, C; Chen, ML; Hou, XF; Li, WQ; Shan, QJ; Xu, DJ; Yang, B; Yu, JB; Zhang, FX; Zhang, R; Zou, JG, 2011)	0.97
"Metoprolol use is essential and its dosage should be individualized in the majority of ICD recipients with ES."	( [Impact of metoprolol use in the treatment of patients with electrical-storm after cardioverter defibrillators implantation]. Cao, KJ; Chen, C; Chen, ML; Hou, XF; Li, WQ; Shan, QJ; Xu, DJ; Yang, B; Yu, JB; Zhang, FX; Zhang, R; Zou, JG, 2011)	2.2
" An individually titrated metoprolol dosage (75-300 mg) was used."	( A controlled study on the antihypertensive effect of a new beta-adrenergic receptor blocking drug, metoprolol, in combination with chlorthalidone. Jäättelä, A; Pyörälä, K, 1976)	0.77
" The two beta-adrenoceptor antagonists were given at two dose levels, practolol (200 mg and 400 mg) daily, and metoprolol (100 mg and 200 mg) daily, in a twice-daily dosage schedule, at 12 h intervals, for 17 days."	( The effect of metoprolol and practolol on lung function and blood pressure in hypertensive asthmatics. Formgren, H, 1976)	0.83
" Cardiac dysfunction in C57BL/6J mice was induced by implantation of osmotic pumps for continuous subcutaneous dosing of angiotensin II (1."	( Role of heart rate reduction in the prevention of experimental heart failure: comparison between If-channel blockade and β-receptor blockade. Becher, PM; Lindner, D; Miteva, K; Savvatis, K; Schmack, B; Schultheiss, HP; Tschöpe, C; Van Linthout, S; Westermann, D; Zietsch, C, 2012)	0.38
"The aim of this study was to develop a multilayer (core/coat) dosage form via co-extrusion, the core providing sustained drug release and the coat immediate drug release."	( Co-extrusion as manufacturing technique for fixed-dose combination mini-matrices. Almeida, A; De Beer, T; Dierickx, L; Remon, JP; Saerens, L; Vervaet, C, 2012)	0.38
"Metoprolol, a cardioselective β-blocker, is well absorbed in colon after oral administration with mean elimination half life of 3 h with bioavailability 50% due to extensive first pass effect, thus it was aimed to develop its modified release dosage form to reduce dosing frequency."	( Eudragit FS based colonic microparticls of metoprolol tartrate. Ahmad, M; Khan, HM; Khan, SA; Murtaza, G; Rasool, F, )	1.84
"The current manuscript reports the first capillary electrophoresis method for the separation and quantification of metoprolol (MET) and hydrochlorothiazide (HCT) in their combined dosage form."	( Capillary electrophoresis assay method for metoprolol and hydrochlorothiazide in their combined dosage form with multivariate optimization. Aldughaish, AM; Alnajjar, AO; Attimarad, MV; Elgorashe, RE; Idris, AM, 2013)	0.86
" They further investigated whether differences in DOS heart rate between atenolol and metoprolol could be explained by once-daily versus twice-daily dosing regimens."	( Atenolol is associated with lower day-of-surgery heart rate compared to long- and short-acting metoprolol. Brandt, C; Burg, MM; Dai, F; Feinleib, J; Schonberger, RB, 2013)	0.83
" The heart rate difference is specific to the day of surgery and is not explained by once-daily versus twice-daily dosing regimens."	( Atenolol is associated with lower day-of-surgery heart rate compared to long- and short-acting metoprolol. Brandt, C; Burg, MM; Dai, F; Feinleib, J; Schonberger, RB, 2013)	0.61
"Here we evaluate poly(2-ethyl-2-oxazoline)s (PEtOx) as a matrix excipient for the production of oral solid dosage forms by hot melt extrusion (HME) followed by injection molding (IM)."	( Poly(2-ethyl-2-oxazoline) as matrix excipient for drug formulation by hot melt extrusion and injection molding. Claeys, B; De Geest, BG; Hoogenboom, R; Remon, JP; Vervaeck, A; Vervaet, C, 2012)	0.38
" The approach to distinguishing the differences between pharmaceutical dosage forms produced by different manufacturers is proposed."	( [The methods for the protection against counterfeit medications. Part 1. The estimation of the quality of metoprolol succinate substance and tablets from different manufacturers in terms of "identity" and "active ingredient content"]. Elizarova, TE; Fitilev, SB; Iakushev, VA; Morozova, MA; Pletneva, TV, )	0.34
" The purpose of this research was to inform selection of an appropriate pre-specified primary dose-response analysis to demonstrate drug efficacy in a registration trial."	( Improper selection of a pre-specified primary dose-response analysis delays regulatory drug approval. Gobburu, J; Jadhav, P; Liu, J; Wang, Y, 2013)	0.39
" Huperzine A's permeability characteristics pave the way to the development of its oral extended release dosage form."	( Transepithelial transport of a natural cholinesterase inhibitor, huperzine A, along the gastrointestinal tract: the role of ionization on absorption mechanism. Burshtein, G; Friedman, M; Greenberg, S; Hoffman, A, 2013)	0.39
"To develop a pharmacokinetic model able to describe the nonlinear pharmacokinetics of paroxetine (PRX) and to predict the drug-drug interaction between PRX and metoprolol under various dosage regimens."	( Pharmacokinetic model incorporating mechanism-based inactivation of CYP2D6 can explain both non-linear kinetics and drug interactions of paroxetine. Hori, S; Mikami, A; Ohtani, H; Sawada, Y, 2013)	0.59
" Using the developed model and estimated parameters, an optimal dosage regimen for metoprolol during withdrawal of PRX was simulated."	( Pharmacokinetic model incorporating mechanism-based inactivation of CYP2D6 can explain both non-linear kinetics and drug interactions of paroxetine. Hori, S; Mikami, A; Ohtani, H; Sawada, Y, 2013)	0.61
" Upon tapering PRX from 20 mg/ day to 10 mg/day for 14 days then 5 mg/day for 14 days until cessation, the optimal dosage regimen to resume 120 mg/day of metoprolol based on the developed model was as follows: 30 mg/day during concomitant administration, 40 mg/day for the next 14 days, 60 mg/day for the next 14 days, and finally 120 mg/day."	( Pharmacokinetic model incorporating mechanism-based inactivation of CYP2D6 can explain both non-linear kinetics and drug interactions of paroxetine. Hori, S; Mikami, A; Ohtani, H; Sawada, Y, 2013)	0.59
"The developed model enabled us to quantitatively estimate drug-drug interactions of PRX and CYP2D6 substrate drugs, and to predict optimal dosage regimens."	( Pharmacokinetic model incorporating mechanism-based inactivation of CYP2D6 can explain both non-linear kinetics and drug interactions of paroxetine. Hori, S; Mikami, A; Ohtani, H; Sawada, Y, 2013)	0.39
"In this study, prilling was evaluated as a technique for the development of multiparticulate dosage forms using the fatty acids, stearic acid, and behenic acid as potential matrix formers to control the release of metoprolol tartrate (MPT), a highly water soluble drug."	( Prilling of fatty acids as a continuous process for the development of controlled release multiparticulate dosage forms. Adriaensens, P; Carleer, R; De Beer, T; De Geest, BG; Remon, JP; Saerens, L; Vervaeck, A; Vervaet, C, 2013)	0.58
" A clear influence of pH on the absorption was seen and a significant higher absolute bioavailability was obtained after buccal dosing (58-107%) compared to oral (3%) administration, ranging 58-107% and 3%, respectively."	( In vitro, ex vivo and in vivo examination of buccal absorption of metoprolol with varying pH in TR146 cell culture, porcine buccal mucosa and Göttingen minipigs. Andersen, MB; Garmer, M; Holm, R; Jacobsen, J; Jespersen, ML; Jørgensen, EB; Karlsson, JJ; Meng-Lund, E, 2013)	0.63
" Each group was further divided randomly into three subgroups, depending on the dosage of epinephrine administered during subsequent CPR applied after the induction of asphyxial cardiac arrest."	( β-Receptor blocker influences return of spontaneous circulation and chemical examination in rats during cardiopulmonary resuscitation. Chen, EX; Gao, YX; Li, LJ; Li, P; Liu, J; Pen, Z; Ren, YX; Zhao, XJ, 2013)	0.39
"A gastric-retentive formulation amenable to dosing in rodents has the potential to enable sustained release in a preclinical setting."	( Utility of gastric-retained alginate gels to modulate pharmacokinetic profiles in rats. Cornelius, G; Dixon, G; Fancher, RM; Ford, K; Foster, KA; Gudmundsson, OS; Hageman, MJ; Proszynski, M; Sun, H, 2013)	0.39
" Pharmacokinetic and pharmacodynamic changes depend on the nature and degree of hepatic impairment and on the characteristics of the dosed drug."	( [Effect of liver cirrhosis on pharmacokinetics and pharmacodynamics of drugs]. Perlík, F, 2013)	0.39
" It is also concluded that level A IVIVC is a proficient mathematical model for biowaiver studies involving study parameters as those implemented for T1S (T1formulation tested for dissolution in the presence of sodium lauryl sulfate) revealing that IVIVC level A is dosage form specific, rather than to be drug specific."	( Development of in vitro-in vivo correlation for encapsulated metoprolol tartrate. Farzana, K; Karim, S; Khaled, AA; Murtaza, G; Pervaiz, K, )	0.37
" This study aims to evaluate if extended-release metoprolol CR/XL once daily gives a similar β-blockade over 24 h compared to multiple dosing of metoprolol IR."	( A pharmacokinetic and pharmacodynamic comparison of immediate-release metoprolol and extended-release metoprolol CR/XL in patients with suspected acute myocardial infarction: a randomized, open-label study. Aberg, J; Dellborg, M; Gullestad, L; Herlitz, J; Karlson, BW; Sugg, J, 2014)	0.89
"Metoprolol CR/XL 200 mg once daily showed lower peak and less variation in peak to trough plasma levels compared to multiple dosing of metoprolol IR with the same AUC."	( A pharmacokinetic and pharmacodynamic comparison of immediate-release metoprolol and extended-release metoprolol CR/XL in patients with suspected acute myocardial infarction: a randomized, open-label study. Aberg, J; Dellborg, M; Gullestad, L; Herlitz, J; Karlson, BW; Sugg, J, 2014)	2.08
" The aim of this study was to evaluate anaesthetised and conscious Göttingen mini-pigs as a model for buccal drug absorption by testing pH-dependent absorption of metoprolol from a solid dosage form."	( Conscious and anaesthetised Göttingen mini-pigs as an in-vivo model for buccal absorption - pH-dependent absorption of metoprolol from bioadhesive tablets. Andersen, MB; Garmer, M; Holm, R; Jacobsen, J; Jespersen, ML; Jørgensen, EB; Karlsson, JJ; Meng-Lund, E, 2014)	0.81
" Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release."	( Development of hollow/porous floating beads of metoprolol for pulsatile drug delivery. Dandagi, PM; Mastiholimath, VS; Taranalli, SS, 2015)	0.67
"This study focused on the evaluation of prilling as a technique for the manufacturing of multiparticulate dosage forms."	( Prilling as manufacturing technique for multiparticulate lipid/PEG fixed-dose combinations. De Beer, T; Monteyne, T; Remon, JP; Saerens, L; Vervaeck, A; Vervaet, C, 2014)	0.4
" Following dosing with PA, some subjects experienced rises in liver function tests above the upper limit of normal during the first few days following PA administration."	( Pharmacokinetic interaction between pyronaridine-artesunate and metoprolol. Arbe-Barnes, S; Borghini-Fuhrer, I; Duparc, S; Fleckenstein, L; Lopez-Lazaro, L; Miller, RM; Morris, CA; Pokorny, R; Shin, JS, 2014)	0.64
" However, constant drug release rates are difficult to achieve with this type of dosage forms if the drug is freely water-soluble."	( How to easily provide zero order release of freely soluble drugs from coated pellets. Dekyndt, B; Neut, C; Siepmann, F; Siepmann, J; Verin, J, 2015)	0.42
"This study evaluated thermoplastic polyurethanes (TPUR) as matrix excipients for the production of oral solid dosage forms via hot melt extrusion (HME) in combination with injection molding (IM)."	( Thermoplastic polyurethanes for the manufacturing of highly dosed oral sustained release matrices via hot melt extrusion and injection molding. Claeys, B; De Beer, T; Hansen, L; Hillewaere, XK; Possemiers, S; Remon, JP; Vervaeck, A; Vervaet, C, 2015)	0.42
" It is a major determinant of half-life and dosing frequency of a drug."	( Volume of Distribution in Drug Design. Beaumont, K; Di, L; Maurer, TS; Smith, DA, 2015)	0.42
" Due to the increasing frequency with which ILE and HIE are being used for the treatment of β-blocker overdose, clinicians should be aware of their dosing strategies and indications."	( Successful treatment of a massive metoprolol overdose using intravenous lipid emulsion and hyperinsulinemia/euglycemia therapy. Barton, CA; Beauchamp, G; Hendrickson, R; Johnson, NB; Mah, ND, 2015)	0.7
" We present an analysis that identifies metoprolol's jejunal permeability as the low/high permeability class benchmark anywhere throughout the intestinal tract; we show that the permeability of both glipizide and metoprolol matches/exceeds this threshold throughout the entire intestinal tract, accounting for their success as controlled-release dosage form."	( The biopharmaceutics of successful controlled release drug product: Segmental-dependent permeability of glipizide vs. metoprolol throughout the intestinal tract. Agbaria, R; Cohen, N; Dahan, A; Zur, M, 2015)	0.89
" After 2 weeks' exposure to DM at low dosage (5 mg/kg), biochemical parameters of hepatic functions were measured, histology and CYP450 expressed in liver was detected."	( Effect of Dimethoate on the Activity of Hepatic CYP450 Based on Pharmacokinetics of Probe Drugs. Hu, L; Lin, F; Tang, M; Zheng, Y; Zhuang, Z, 2015)	0.42
"A low dosage of DM could induce the activity of CYP2D1 in liver and increase the metabolism of metoprolol when exposed for 2 weeks."	( Effect of Dimethoate on the Activity of Hepatic CYP450 Based on Pharmacokinetics of Probe Drugs. Hu, L; Lin, F; Tang, M; Zheng, Y; Zhuang, Z, 2015)	0.64
" The dosage of carvedilol had no detectable effect and there were no unexpected safety issues."	( Effect of Combining Ivabradine and β-Blockers: Focus on the Use of Carvedilol in the SHIFT Population. Bocchi, EA; Böhm, M; Borer, JS; Ford, I; Komajda, M; Swedberg, K; Tavazzi, L, 2015)	0.42
" A panel of pharmaceutical quality tests was also performed on three batches of Lamictal, three batches of Teva generic, and one batch of each of four other generics: appearance, identity, assay, impurity, uniformity of dosage units, disintegration, dissolution, friability, and loss on drying."	( Biopharmaceutic Risk Assessment of Brand and Generic Lamotrigine Tablets. Jiang, W; Kane, MA; Polli, JE; Raman, S; Ting, TY; Vaithianathan, S, 2015)	0.42
" The method has been validated according to International Conference on Harmonization guidelines and has been successfully applied for determination of the studied drugs in their dosage forms without interference from commonly encountered excipients."	( Development and validation of TLC-densitometric method for simultaneous determination of two binary antihypertensive mixtures containing felodipine in fixed dose combinations. Hammad, MA; Mohamed, AA; Mohamed, AM; Omar, MA, 2016)	0.43
" In vitro metoprolol tartrate release from the ethylcellulose core of the calendered tablets was prolonged in comparison with the sustained release of a multiparticulate dosage form, prepared manually by cutting co-extrudates into mini-matrices."	( Calendering as a direct shaping tool for the continuous production of fixed-dose combination products via co-extrusion. Bongaers, E; Lin, H; Remon, JP; Vervaet, C; Voorspoels, J; Vynckier, AK; Willart, JF; Zeitler, JA, 2015)	0.82
" Serial plasma, urine, and breast milk concentrations of metoprolol and its metabolite, α-hydroxymetoprolol, were measured over 1 dosing interval in women treated with metoprolol (25-750 mg/day) during early pregnancy (n = 4), mid-pregnancy (n = 14), and late pregnancy (n = 15), as well as postpartum (n = 9) with (n = 4) and without (n = 5) lactation."	( Pharmacokinetics of metoprolol during pregnancy and lactation. Caritis, SN; Easterling, TR; Eyal, S; Hankins, G; Hebert, MF; Honaker, MT; Kelly, EJ; Phillips, B; Risler, L; Rytting, E; Ryu, RJ; Shen, DD; Thummel, K; Venkataraman, R, 2016)	1
" The floating bilayer tablets of lisinopril maleate and metoprolol tartrate were designed to overcome the various problems associated with conventional oral dosage form."	( Formulation and in-vitro evaluation of floating bilayer tablet of lisinopril maleate and metoprolol tartrate. Abdel-Daim, M; Danish, Z; Hanif, M; Ijaz, H; Mohammad, IS; Qureshi, J; Waheed, I; Zaman, M, 2015)	0.88
"Ethylcellulose is one of the most commonly used polymers to develop reservoir type extended release multiparticulate dosage forms."	( Investigation into the Effect of Ethylcellulose Viscosity Variation on the Drug Release of Metoprolol Tartrate and Acetaminophen Extended Release Multiparticulates-Part I. Ferrizzi, D; Mehta, R; Rajabi-Siahboomi, A; Schoener, C; Teckoe, J; Workentine, S, 2016)	0.65
"There is not enough evidence to support or discourage the use of beta-blockers in children with congestive heart failure, or to propose a paediatric dosing scheme."	( Beta-blockers for congestive heart failure in children. Al Dakhoul, S; Alabed, S; Bdaiwi, Y; Frobel-Mercier, AK; Sabouni, A, 2016)	0.43
" After adjustment for age, sex, comorbidities, and severity of HF and COPD, bisoprolol use showed a dose-response survival benefit [low dose: adjusted hazard ratio (HR) = 0."	( Carvedilol, Bisoprolol, and Metoprolol Use in Patients With Coexistent Heart Failure and Chronic Obstructive Pulmonary Disease. Chang, YS; Chen, TJ; Chou, KT; Hu, YW; Hung, MH; Lee, FY; Liu, CJ; Ou, SM; Perng, DW; Su, VY; Yang, KY, 2016)	0.73
"The median daily dosage of RIS did not differ between the groups (p=0."	( Pharmacokinetic considerations in the treatment of hypertension in risperidone-medicated patients - thinking of clinically relevant CYP2D6 interactions. Gründer, G; Haen, E; Lammertz, SE; Paulzen, M; Schoretsanitis, G; Schruers, KR; Stegmann, B; Walther, S, 2016)	0.43
"The development of oral modified-release (MR) dosage forms requires an active pharmaceutical ingredient (API) with a sufficiently high absorption rate in both the small and large intestine."	( Regional Intestinal Permeability in Dogs: Biopharmaceutical Aspects for Development of Oral Modified-Release Dosage Forms. Abrahamsson, B; Dahlgren, D; Johansson, P; Lennernäs, H; Lundqvist, A; Roos, C; Sjögren, E; Tannergren, C, 2016)	0.43
" This has hindered the validation of preclinical models with regard to absorption in the distal parts of the intestinal tract, which can be substantial for BCS class II-IV drugs, and drugs formulated into modified-release (MR) dosage forms."	( Regional Intestinal Permeability of Three Model Drugs in Human. Abrahamsson, B; Dahlgren, D; Hellström, PM; Lennernäs, H; Lundqvist, A; Roos, C; Sjögren, E; Tannergren, C, 2016)	0.43
" Except for the dosage of noradrenaline (0."	( Propafenone for supraventricular arrhythmias in septic shock-Comparison to amiodarone and metoprolol. Balik, M; Kolnikova, I; Kristof, J; Maly, M; Tavazzi, G; Waldauf, P, 2017)	0.68
"Knowledge about the region-specific absorption profiles from the gastrointestinal tract of orally administered drugs is a critical factor guiding dosage form selection in drug development."	( Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis. Andrén, PE; Goodwin, RJA; Hayes, MA; Hilgendorf, C; Nilsson, A; Peric, A; Strimfors, M, 2017)	0.46
"Controlled release dosage forms provide sustained therapeutics effects for prolonged period of time and improve patient compliance."	( Formulation and in vitro evaluation of directly compressed controlled release tablets designed from the Co-precipitates. Jan, SU; Khan, GM; Khan, KA; Mehsud, S; Rehman, A, 2018)	0.48
"8 months was analysed with respect to beta blocker dosing and resting HR."	( Beta blockers and chronic heart failure patients: prognostic impact of a dose targeted beta blocker therapy vs. heart rate targeted strategy. Corletto, A; Frankenstein, L; Fröhlich, H; Hochadel, M; Katus, HA; Kilkowski, C; Senges, J; Täger, T; Winkler, R; Zahn, R, 2018)	0.48
"The current study reports on the manufacturing of extended release dosage forms of metoprolol succinate via hot-melt extrusion (HME) technology."	( Extended release delivery system of metoprolol succinate using hot-melt extrusion: effect of release modifier on methacrylic acid copolymer. Amin, PD; Fule, R; Maniruzzaman, M; Sawant, KP, 2018)	0.98
"With the use of the cohort of 15,205 Medicare beneficiaries hospitalized for HFrEF from 2007 to 2013 in the 5% Medicare random sample, we described prescription fills (30 days after discharge) and dosage patterns (1 year after discharge) for beta-blockers."	( Low Utilization of Beta-Blockers Among Medicare Beneficiaries Hospitalized for Heart Failure With Reduced Ejection Fraction. Brown, TM; Chen, L; Durant, RW; Kilgore, ML; Levitan, EB; Loop, MS; Safford, MM; van Dyke, MK, 2019)	0.51
" The robust, scalable technology presented in this study offers an important solution to the long-standing challenges of formulating sustained-release dosage forms suitable for children and older people with swallowing difficulties."	( Wurster Fluidised Bed Coating of Microparticles: Towards Scalable Production of Oral Sustained-Release Liquid Medicines for Patients with Swallowing Difficulties. Liu, F; Mohylyuk, V; Murnane, D; Patel, K; Richardson, C; Scott, N, 2019)	0.51
" Based on the Chinese and International guidelines and the Chinese clinical practice, we are conducting this study (NCT03413410) to test the feasibility and tolerability of the metoprolol optimal dosing pathway by observing the percentage of patients achieving target dose in Chinese acute coronary syndrome (ACS) patients during hospitalisation."	( Impact of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome: protocol for a multicentre prospective study. Chen, Y; Dong, W; Li, D; Liu, Y; Mu, Y; Wang, J; Zhou, H; Zhou, S, 2019)	1.11
" The percentage of patients achieving the target metoprolol dosage at discharge is the primary endpoint."	( Impact of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome: protocol for a multicentre prospective study. Chen, Y; Dong, W; Li, D; Liu, Y; Mu, Y; Wang, J; Zhou, H; Zhou, S, 2019)	1.17
" Adults aged 18 years or above diagnosed with probable or definitive VM according to the Neuhauser criteria 2001 were randomly assigned 1:1 to 6 months blinded metoprolol (maintenance dosage of 95 mg daily) or placebo."	( Results and lessons learnt from a randomized controlled trial: prophylactic treatment of vestibular migraine with metoprolol (PROVEMIG). Adrion, C; Al Tawil, A; Bayer, O; Mansmann, U; Strupp, M, 2019)	0.92
" At follow-up, metoprolol dosage after up-titration, metoprolol steady-state trough plasma concentrations, hemodynamic parameters, potential metoprolol-induced adverse drug reactions and number of visits to the GP were measured."	( Impact of genotype-predicted CYP2D6 metabolism on clinical effects and tolerability of metoprolol in patients after myocardial infarction - a prospective observational study. Anstensrud, AK; Fosshaug, LE; Haug, HJ; Molden, E; Muriq, H; Qazi, R; Spigset, O; Øie, E, 2020)	1.13
" Insulin was infused for a total of approximately 37 hours, most of which was dosed at 10 U/kg/hour; following discontinuation, serial serum insulin levels were drawn and remained at supraphysiologic levels for at least 24 hours and well above reference range for multiple days thereafter."	( Persistent Hyperinsulinemia Following High-Dose Insulin Therapy: A Case Report. Bangh, SA; Cole, JB; Corcoran, JN; Jacoby, KJ; Olives, TD, 2020)	0.56
"Application of capillary electrophoresis (CE) has become a rapidly growing analytical technique for the estimation of drugs in pharmaceutical dosage forms and biological fluids."	( Capillary Electrophoresis Method for Determination of Escitalopram Oxalate in Urine Samples and Different Dosage Forms. Arlı, G; Atkoşar, Z; Badulla, WFS; Dal Poçan, AG, 2020)	0.56
"There is not enough evidence to support or discourage the use of beta-blockers in children with congestive heart failure, or to propose a paediatric dosing scheme."	( Beta-blockers for congestive heart failure in children. Al Dakhoul, S; Alabed, S; Bdaiwi, Y; Sabouni, A, 2020)	0.56
" An efficient and sensitive method to measure multiple serum drugs and metabolites could inform drug dosing in polypharmacy."	( Quantification of serum levels in mice of seven drugs (and six metabolites) commonly taken by older people with polypharmacy. Hilmer, SN; Mach, J; Wang, X, 2021)	0.62
" The dosage of BETALOC® was administered to subjects following single and multiple doses and its active ingredient metoprolol and its main metabolite α-hydroxyl metoprolol were selected as the analytes."	( Simultaneous time-course measurements of metoprolol and α-hydroxyl metoprolol in fingermarks after oral administration by liquid chromatography tandem mass spectrometry. Zhang, WJ, 2020)	1.03
"The development and evaluation of a controlled-release (CR) pharmaceutical solid dosage form comprising xanthan gum (XG), low molecular weight chitosan (LCS), and metoprolol succinate (MS) are reported."	( Elucidation of the Controlled-Release Behavior of Metoprolol Succinate from Directly Compressed Xanthan Gum/Chitosan Polymers: Computational and Experimental Studies. Antonijevic, MD; Badwan, AA; Chowdhry, BZ; Dadou, SM; El-Barghouthi, MI, 2020)	1.01
" Beta-blocker dosage groups were >0% to12."	( Comparison of Metoprolol Versus Carvedilol After Acute Myocardial Infarction. Fintel, DJ; Germano, JJ; Goldberger, JJ; Shani, J; Subacius, H; Zaatari, G, 2021)	0.98
"Current guidelines have no sex-specific dosage advice for metoprolol."	( Women are started on a lower daily dose of metoprolol than men irrespective of dose recommendations: A potential source of confounding by contraindication in pharmacoepidemiology. Hendriksen, LC; Stricker, BH; Van der Linden, PD; Verhamme, KMC; Visser, LE, 2021)	1.13
"The plasma concentrations of metoprolol were determined using Reverse Phase-High Performance Liquid Chromatography (RP-HPLC) on the 1st day in single-dose pharmacokinetic (PK) study (SDS) and on the 15th day in multiple dosing PK studies (MDS)."	( Effect of naringenin on the pharmacokinetics of metoprolol succinate in rats. Dirisala, VR; Gullapalli, Y; Kilaru, NB; Mullapudi, SS; Pingili, RB; Vemulapalli, S, 2021)	1.17
" Such cohorts have not been commonly used to identify genetic predictors of drug dosing or concentrations, perhaps because of the heterogeneity in drug dosing and formulation, and the random timing of blood sampling."	( Leveraging large observational studies to discover genetic determinants of drug concentrations: A proof-of-concept study. Busseuil, D; de Denus, S; Dubé, MP; Gaulin, MJ; Jutras, M; Leclair, G; Meloche, M; Mongrain, I; Oussaïd, E; Tardif, JC, 2022)	0.72
"We found a five-fold increased risk of delivering a small-for-gestational-age infant in women with heart disease treated with a high dose of beta-blocker, and a two-fold increased risk among those treated with a low dose, showing an apparent dose-response relation."	( Maternal beta-blocker dose and risk of small-for gestational-age in women with heart disease. Estensen, ME; Haualand, R; Langesaeter, E; Letting, AS; Sørbye, IK; Wiull, H, 2022)	0.72
" Small and mostly insignificant differences in average daily metoprolol dosage were found between patients treated with the various antidepressants."	( Co-prescription of metoprolol and CYP2D6-inhibiting antidepressants before and after implementation of an optimized drug interaction database in Norway. Gedde-Dahl, A; Molden, E; Spigset, O, 2022)	1.29
" The aim of this study was to investigate whether anthropometric and socioeconomic factors and comorbidities could explain sex-related differences in concentrations and dosing for metoprolol and oxypurinol, the active metabolite of allopurinol."	( Females present higher dose-adjusted drug concentrations of metoprolol and allopurinol/oxypurinol than males. Busseuil, D; de Denus, S; Dubé, MP; Gaulin, MJ; Hindi, J; Jutras, M; Leclair, G; Meloche, M; Mongrain, I; Oussaïd, E; Pilon, MO; Rouleau, JL; St-Jean, I; Tardif, JC, 2023)	1.34
" This study assesses the impact of β-blocker type and dosing on survival in patients with DM after MI."	( Impact of Diabetes Mellitus on Benefit of β-Blocker Therapy After Myocardial Infarction. Abbott, JD; Bello, D; Blandon, C; Goldberger, JJ; Subačius, H; Zaatari, G, 2023)	0.91
" The developed methods are accurate, precise, eco-friendly and could be applied successfully to estimate OLM and MET in their combined dosage form."	( Area under the curve and ratio difference spectrophotometric methods with evaluation of the greenness for simultaneous determination of olmesartan medoxomil and metoprolol succinate. Hammad, SF; Kamal, AH; Kamel, DN, 2023)	1.11

Role	Description
beta-adrenergic antagonist	An agent that binds to but does not activate beta-adrenergic receptors thereby blocking the actions of endogenous or exogenous beta-adrenergic agonists. beta-Adrenergic antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches and anxiety.
antihypertensive agent	Any drug used in the treatment of acute or chronic vascular hypertension regardless of pharmacological mechanism.
xenobiotic	A xenobiotic (Greek, xenos "foreign"; bios "life") is a compound that is foreign to a living organism. Principal xenobiotics include: drugs, carcinogens and various compounds that have been introduced into the environment by artificial means.
environmental contaminant	Any minor or unwanted substance introduced into the environment that can have undesired effects.
geroprotector	Any compound that supports healthy aging, slows the biological aging process, or extends lifespan.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Class	Description
propanolamine
aromatic ether	Any ether in which the oxygen is attached to at least one aryl substituent.
secondary alcohol	A secondary alcohol is a compound in which a hydroxy group, -OH, is attached to a saturated carbon atom which has two other carbon atoms attached to it.
secondary amino compound	A compound formally derived from ammonia by replacing two hydrogen atoms by organyl groups.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathway	Proteins	Compounds
Metoprolol Action Pathway	47	8

Protein	Taxonomy	Measurement	Average (µ)	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
estrogen receptor 2 (ER beta)	Homo sapiens (human)	Potency	43.2771	0.0006	57.9133	22,387.1992	AID1259378
estrogen-related nuclear receptor alpha	Homo sapiens (human)	Potency	61.1306	0.0015	30.6073	15,848.9004	AID1224848; AID1224849
thioredoxin reductase	Rattus norvegicus (Norway rat)	Potency	0.3981	0.1000	20.8793	79.4328	AID588453
euchromatic histone-lysine N-methyltransferase 2	Homo sapiens (human)	Potency	63.0957	0.0355	20.9770	89.1251	AID504332
Bloom syndrome protein isoform 1	Homo sapiens (human)	Potency	0.0006	0.5406	17.6392	96.1227	AID2364; AID2528
peripheral myelin protein 22 isoform 1	Homo sapiens (human)	Potency	11.9955	23.9341	23.9341	23.9341	AID1967
histone acetyltransferase KAT2A isoform 1	Homo sapiens (human)	Potency	39.8107	0.2512	15.8432	39.8107	AID504327
neuropeptide S receptor isoform A	Homo sapiens (human)	Potency	0.0501	0.0158	12.3113	615.5000	AID1461
ATP-dependent phosphofructokinase	Trypanosoma brucei brucei TREU927	Potency	23.9341	0.0601	10.7453	37.9330	AID485368
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
ATP-binding cassette sub-family C member 3	Homo sapiens (human)	IC50 (µMol)	133.0000	0.6315	4.4531	9.3000	AID1473740
Multidrug resistance-associated protein 4	Homo sapiens (human)	IC50 (µMol)	133.0000	0.2000	5.6774	10.0000	AID1473741
Bile salt export pump	Homo sapiens (human)	IC50 (µMol)	134.0000	0.1100	7.1903	10.0000	AID1443980; AID1473738
Beta-2 adrenergic receptor	Homo sapiens (human)	IC50 (µMol)	2.5730	0.0002	0.9326	7.2000	AID625205
Beta-2 adrenergic receptor	Homo sapiens (human)	Ki	0.9945	0.0000	0.6635	9.5499	AID1603579; AID625205
ATP-dependent translocase ABCB1	Homo sapiens (human)	IC50 (µMol)	1,300.0000	0.0002	2.3185	10.0000	AID150618
ATP-dependent translocase ABCB1	Homo sapiens (human)	Ki	200.0000	0.0200	2.3594	8.5900	AID150735
Beta-1 adrenergic receptor	Homo sapiens (human)	IC50 (µMol)	0.1760	0.0002	1.4681	9.0000	AID625204
Beta-1 adrenergic receptor	Homo sapiens (human)	Ki	0.0785	0.0001	1.3391	9.9840	AID1603580; AID625204
Cytochrome P450 2D6	Homo sapiens (human)	IC50 (µMol)	24.0000	0.0000	2.0151	10.0000	AID241889
Cytochrome P450 2C9	Homo sapiens (human)	IC50 (µMol)	4.8700	0.0000	2.8005	10.0000	AID1210069
Beta-1 adrenergic receptor	Rattus norvegicus (Norway rat)	Ki	2.2129	0.0000	0.6673	10.0000	AID266006; AID266007; AID266008; AID266009; AID266010
5-hydroxytryptamine receptor 1A	Rattus norvegicus (Norway rat)	Ki	10.0000	0.0001	0.7396	10.0000	AID4411
Beta-1 adrenergic receptor	Mus musculus (house mouse)	Ki	0.0490	0.0001	0.1310	0.5500	AID1603578
Cytochrome P450 2J2	Homo sapiens (human)	IC50 (µMol)	4.8700	0.0120	2.5312	9.4700	AID1210069
Canalicular multispecific organic anion transporter 1	Homo sapiens (human)	IC50 (µMol)	133.0000	2.4100	6.3433	10.0000	AID1473739
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Beta-1 adrenergic receptor	Cavia porcellus (domestic guinea pig)	Kd	0.2513	0.0000	0.5358	8.3176	AID39943; AID42210; AID42214
Gamma-aminobutyric acid receptor subunit pi	Rattus norvegicus (Norway rat)	Kd	0.1622	0.0002	0.5629	4.4668	AID40869
Beta-2 adrenergic receptor	Homo sapiens (human)	Kd	4.5460	0.0000	0.6288	8.9130	AID1626022; AID1626023; AID1798580
Beta-1 adrenergic receptor	Homo sapiens (human)	Kd	1.7790	0.0001	0.8039	10.0000	AID1232324; AID1798580
Beta-3 adrenergic receptor	Homo sapiens (human)	Kd	2.3667	0.0001	0.7631	8.9130	AID1798580
Gamma-aminobutyric acid receptor subunit beta-1	Rattus norvegicus (Norway rat)	Kd	0.1622	0.0002	0.5629	4.4668	AID40869
Beta-1 adrenergic receptor	Rattus norvegicus (Norway rat)	Kd	0.0229	0.0014	0.0601	0.3910	AID1318766; AID40420; AID40527
Gamma-aminobutyric acid receptor subunit delta	Rattus norvegicus (Norway rat)	Kd	0.1622	0.0002	0.5629	4.4668	AID40869
Gamma-aminobutyric acid receptor subunit gamma-2	Rattus norvegicus (Norway rat)	Kd	0.1622	0.0002	0.5629	4.4668	AID40869
5-hydroxytryptamine receptor 1A	Rattus norvegicus (Norway rat)	Kd	0.1622	0.0001	2.2933	8.5114	AID40869
Gamma-aminobutyric acid receptor subunit alpha-5	Rattus norvegicus (Norway rat)	Kd	0.1622	0.0002	0.5629	4.4668	AID40869
Gamma-aminobutyric acid receptor subunit alpha-3	Rattus norvegicus (Norway rat)	Kd	0.1622	0.0002	0.5629	4.4668	AID40869
Gamma-aminobutyric acid receptor subunit gamma-1	Rattus norvegicus (Norway rat)	Kd	0.1622	0.0002	0.5629	4.4668	AID40869
Gamma-aminobutyric acid receptor subunit alpha-2	Rattus norvegicus (Norway rat)	Kd	0.1622	0.0002	0.5629	4.4668	AID40869
Gamma-aminobutyric acid receptor subunit alpha-4	Rattus norvegicus (Norway rat)	Kd	0.1622	0.0002	0.5629	4.4668	AID40869
Gamma-aminobutyric acid receptor subunit gamma-3	Rattus norvegicus (Norway rat)	Kd	0.1622	0.0002	0.5629	4.4668	AID40869
Gamma-aminobutyric acid receptor subunit alpha-6	Rattus norvegicus (Norway rat)	Kd	0.1622	0.0002	0.5629	4.4668	AID40869
Gamma-aminobutyric acid receptor subunit alpha-1	Rattus norvegicus (Norway rat)	Kd	0.1622	0.0002	0.5629	4.4668	AID40869
Gamma-aminobutyric acid receptor subunit beta-3	Rattus norvegicus (Norway rat)	Kd	0.1622	0.0002	0.5629	4.4668	AID40869
Gamma-aminobutyric acid receptor subunit beta-2	Rattus norvegicus (Norway rat)	Kd	0.1622	0.0002	0.5629	4.4668	AID40869
Beta-2 adrenergic receptor	Cavia porcellus (domestic guinea pig)	Kd	0.1622	0.0002	0.5477	4.4668	AID40868; AID40869; AID40870
GABA theta subunit	Rattus norvegicus (Norway rat)	Kd	0.1622	0.0002	0.5629	4.4668	AID40869
Gamma-aminobutyric acid receptor subunit epsilon	Rattus norvegicus (Norway rat)	Kd	0.1622	0.0002	0.5629	4.4668	AID40869
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
ATP-dependent translocase ABCB1	Homo sapiens (human)	Ki1	200.0000	0.1100	2.0267	5.5000	AID681382
ATP-dependent translocase ABCB1	Homo sapiens (human)	Ki2	1,750.0000	3.4000	3.4000	3.4000	AID681382
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Process	via Protein(s)	Taxonomy
xenobiotic metabolic process	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
xenobiotic transmembrane transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
bile acid and bile salt transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
glucuronoside transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
xenobiotic transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
transmembrane transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
leukotriene transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
monoatomic anion transmembrane transport	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
transport across blood-brain barrier	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
prostaglandin secretion	Multidrug resistance-associated protein 4	Homo sapiens (human)
cilium assembly	Multidrug resistance-associated protein 4	Homo sapiens (human)
platelet degranulation	Multidrug resistance-associated protein 4	Homo sapiens (human)
xenobiotic metabolic process	Multidrug resistance-associated protein 4	Homo sapiens (human)
xenobiotic transmembrane transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
bile acid and bile salt transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
prostaglandin transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
urate transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
glutathione transmembrane transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
transmembrane transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
cAMP transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
leukotriene transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
monoatomic anion transmembrane transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
export across plasma membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
transport across blood-brain barrier	Multidrug resistance-associated protein 4	Homo sapiens (human)
guanine nucleotide transmembrane transport	Multidrug resistance-associated protein 4	Homo sapiens (human)
fatty acid metabolic process	Bile salt export pump	Homo sapiens (human)
bile acid biosynthetic process	Bile salt export pump	Homo sapiens (human)
xenobiotic metabolic process	Bile salt export pump	Homo sapiens (human)
xenobiotic transmembrane transport	Bile salt export pump	Homo sapiens (human)
response to oxidative stress	Bile salt export pump	Homo sapiens (human)
bile acid metabolic process	Bile salt export pump	Homo sapiens (human)
response to organic cyclic compound	Bile salt export pump	Homo sapiens (human)
bile acid and bile salt transport	Bile salt export pump	Homo sapiens (human)
canalicular bile acid transport	Bile salt export pump	Homo sapiens (human)
protein ubiquitination	Bile salt export pump	Homo sapiens (human)
regulation of fatty acid beta-oxidation	Bile salt export pump	Homo sapiens (human)
carbohydrate transmembrane transport	Bile salt export pump	Homo sapiens (human)
bile acid signaling pathway	Bile salt export pump	Homo sapiens (human)
cholesterol homeostasis	Bile salt export pump	Homo sapiens (human)
response to estrogen	Bile salt export pump	Homo sapiens (human)
response to ethanol	Bile salt export pump	Homo sapiens (human)
xenobiotic export from cell	Bile salt export pump	Homo sapiens (human)
lipid homeostasis	Bile salt export pump	Homo sapiens (human)
phospholipid homeostasis	Bile salt export pump	Homo sapiens (human)
positive regulation of bile acid secretion	Bile salt export pump	Homo sapiens (human)
regulation of bile acid metabolic process	Bile salt export pump	Homo sapiens (human)
transmembrane transport	Bile salt export pump	Homo sapiens (human)
diet induced thermogenesis	Beta-2 adrenergic receptor	Homo sapiens (human)
regulation of sodium ion transport	Beta-2 adrenergic receptor	Homo sapiens (human)
transcription by RNA polymerase II	Beta-2 adrenergic receptor	Homo sapiens (human)
receptor-mediated endocytosis	Beta-2 adrenergic receptor	Homo sapiens (human)
smooth muscle contraction	Beta-2 adrenergic receptor	Homo sapiens (human)
cell surface receptor signaling pathway	Beta-2 adrenergic receptor	Homo sapiens (human)
activation of transmembrane receptor protein tyrosine kinase activity	Beta-2 adrenergic receptor	Homo sapiens (human)
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	Beta-2 adrenergic receptor	Homo sapiens (human)
endosome to lysosome transport	Beta-2 adrenergic receptor	Homo sapiens (human)
response to cold	Beta-2 adrenergic receptor	Homo sapiens (human)
positive regulation of protein kinase A signaling	Beta-2 adrenergic receptor	Homo sapiens (human)
positive regulation of bone mineralization	Beta-2 adrenergic receptor	Homo sapiens (human)
heat generation	Beta-2 adrenergic receptor	Homo sapiens (human)
negative regulation of multicellular organism growth	Beta-2 adrenergic receptor	Homo sapiens (human)
positive regulation of MAPK cascade	Beta-2 adrenergic receptor	Homo sapiens (human)
bone resorption	Beta-2 adrenergic receptor	Homo sapiens (human)
negative regulation of G protein-coupled receptor signaling pathway	Beta-2 adrenergic receptor	Homo sapiens (human)
positive regulation of transcription by RNA polymerase II	Beta-2 adrenergic receptor	Homo sapiens (human)
negative regulation of smooth muscle contraction	Beta-2 adrenergic receptor	Homo sapiens (human)
brown fat cell differentiation	Beta-2 adrenergic receptor	Homo sapiens (human)
positive regulation of mini excitatory postsynaptic potential	Beta-2 adrenergic receptor	Homo sapiens (human)
adrenergic receptor signaling pathway	Beta-2 adrenergic receptor	Homo sapiens (human)
adenylate cyclase-activating adrenergic receptor signaling pathway	Beta-2 adrenergic receptor	Homo sapiens (human)
positive regulation of protein serine/threonine kinase activity	Beta-2 adrenergic receptor	Homo sapiens (human)
positive regulation of cold-induced thermogenesis	Beta-2 adrenergic receptor	Homo sapiens (human)
positive regulation of autophagosome maturation	Beta-2 adrenergic receptor	Homo sapiens (human)
positive regulation of lipophagy	Beta-2 adrenergic receptor	Homo sapiens (human)
cellular response to amyloid-beta	Beta-2 adrenergic receptor	Homo sapiens (human)
response to psychosocial stress	Beta-2 adrenergic receptor	Homo sapiens (human)
positive regulation of cAMP-dependent protein kinase activity	Beta-2 adrenergic receptor	Homo sapiens (human)
positive regulation of AMPA receptor activity	Beta-2 adrenergic receptor	Homo sapiens (human)
norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure	Beta-2 adrenergic receptor	Homo sapiens (human)
G2/M transition of mitotic cell cycle	ATP-dependent translocase ABCB1	Homo sapiens (human)
xenobiotic metabolic process	ATP-dependent translocase ABCB1	Homo sapiens (human)
response to xenobiotic stimulus	ATP-dependent translocase ABCB1	Homo sapiens (human)
phospholipid translocation	ATP-dependent translocase ABCB1	Homo sapiens (human)
terpenoid transport	ATP-dependent translocase ABCB1	Homo sapiens (human)
regulation of response to osmotic stress	ATP-dependent translocase ABCB1	Homo sapiens (human)
transmembrane transport	ATP-dependent translocase ABCB1	Homo sapiens (human)
transepithelial transport	ATP-dependent translocase ABCB1	Homo sapiens (human)
stem cell proliferation	ATP-dependent translocase ABCB1	Homo sapiens (human)
ceramide translocation	ATP-dependent translocase ABCB1	Homo sapiens (human)
export across plasma membrane	ATP-dependent translocase ABCB1	Homo sapiens (human)
transport across blood-brain barrier	ATP-dependent translocase ABCB1	Homo sapiens (human)
positive regulation of anion channel activity	ATP-dependent translocase ABCB1	Homo sapiens (human)
carboxylic acid transmembrane transport	ATP-dependent translocase ABCB1	Homo sapiens (human)
xenobiotic detoxification by transmembrane export across the plasma membrane	ATP-dependent translocase ABCB1	Homo sapiens (human)
xenobiotic transport across blood-brain barrier	ATP-dependent translocase ABCB1	Homo sapiens (human)
regulation of chloride transport	ATP-dependent translocase ABCB1	Homo sapiens (human)
positive regulation of heart rate by epinephrine-norepinephrine	Beta-1 adrenergic receptor	Homo sapiens (human)
positive regulation of the force of heart contraction by epinephrine-norepinephrine	Beta-1 adrenergic receptor	Homo sapiens (human)
diet induced thermogenesis	Beta-1 adrenergic receptor	Homo sapiens (human)
response to cold	Beta-1 adrenergic receptor	Homo sapiens (human)
heat generation	Beta-1 adrenergic receptor	Homo sapiens (human)
negative regulation of multicellular organism growth	Beta-1 adrenergic receptor	Homo sapiens (human)
fear response	Beta-1 adrenergic receptor	Homo sapiens (human)
regulation of circadian sleep/wake cycle, sleep	Beta-1 adrenergic receptor	Homo sapiens (human)
brown fat cell differentiation	Beta-1 adrenergic receptor	Homo sapiens (human)
regulation of postsynaptic membrane potential	Beta-1 adrenergic receptor	Homo sapiens (human)
adenylate cyclase-activating adrenergic receptor signaling pathway	Beta-1 adrenergic receptor	Homo sapiens (human)
positive regulation of cold-induced thermogenesis	Beta-1 adrenergic receptor	Homo sapiens (human)
norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure	Beta-1 adrenergic receptor	Homo sapiens (human)
positive regulation of MAPK cascade	Beta-1 adrenergic receptor	Homo sapiens (human)
xenobiotic metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
steroid metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
cholesterol metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
estrogen metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
coumarin metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
alkaloid metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
alkaloid catabolic process	Cytochrome P450 2D6	Homo sapiens (human)
monoterpenoid metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
isoquinoline alkaloid metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
xenobiotic catabolic process	Cytochrome P450 2D6	Homo sapiens (human)
retinol metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
long-chain fatty acid biosynthetic process	Cytochrome P450 2D6	Homo sapiens (human)
negative regulation of binding	Cytochrome P450 2D6	Homo sapiens (human)
oxidative demethylation	Cytochrome P450 2D6	Homo sapiens (human)
negative regulation of cellular organofluorine metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
arachidonic acid metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
xenobiotic metabolic process	Cytochrome P450 2C9	Homo sapiens (human)
steroid metabolic process	Cytochrome P450 2C9	Homo sapiens (human)
cholesterol metabolic process	Cytochrome P450 2C9	Homo sapiens (human)
estrogen metabolic process	Cytochrome P450 2C9	Homo sapiens (human)
monoterpenoid metabolic process	Cytochrome P450 2C9	Homo sapiens (human)
epoxygenase P450 pathway	Cytochrome P450 2C9	Homo sapiens (human)
urea metabolic process	Cytochrome P450 2C9	Homo sapiens (human)
monocarboxylic acid metabolic process	Cytochrome P450 2C9	Homo sapiens (human)
xenobiotic catabolic process	Cytochrome P450 2C9	Homo sapiens (human)
long-chain fatty acid biosynthetic process	Cytochrome P450 2C9	Homo sapiens (human)
amide metabolic process	Cytochrome P450 2C9	Homo sapiens (human)
icosanoid biosynthetic process	Cytochrome P450 2C9	Homo sapiens (human)
oxidative demethylation	Cytochrome P450 2C9	Homo sapiens (human)
omega-hydroxylase P450 pathway	Cytochrome P450 2C9	Homo sapiens (human)
receptor-mediated endocytosis	Beta-3 adrenergic receptor	Homo sapiens (human)
negative regulation of G protein-coupled receptor signaling pathway	Beta-3 adrenergic receptor	Homo sapiens (human)
diet induced thermogenesis	Beta-3 adrenergic receptor	Homo sapiens (human)
carbohydrate metabolic process	Beta-3 adrenergic receptor	Homo sapiens (human)
generation of precursor metabolites and energy	Beta-3 adrenergic receptor	Homo sapiens (human)
energy reserve metabolic process	Beta-3 adrenergic receptor	Homo sapiens (human)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	Beta-3 adrenergic receptor	Homo sapiens (human)
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	Beta-3 adrenergic receptor	Homo sapiens (human)
response to cold	Beta-3 adrenergic receptor	Homo sapiens (human)
heat generation	Beta-3 adrenergic receptor	Homo sapiens (human)
negative regulation of multicellular organism growth	Beta-3 adrenergic receptor	Homo sapiens (human)
eating behavior	Beta-3 adrenergic receptor	Homo sapiens (human)
positive regulation of MAPK cascade	Beta-3 adrenergic receptor	Homo sapiens (human)
brown fat cell differentiation	Beta-3 adrenergic receptor	Homo sapiens (human)
adenylate cyclase-activating adrenergic receptor signaling pathway	Beta-3 adrenergic receptor	Homo sapiens (human)
positive regulation of cold-induced thermogenesis	Beta-3 adrenergic receptor	Homo sapiens (human)
norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure	Beta-3 adrenergic receptor	Homo sapiens (human)
fatty acid metabolic process	Cytochrome P450 2J2	Homo sapiens (human)
icosanoid metabolic process	Cytochrome P450 2J2	Homo sapiens (human)
xenobiotic metabolic process	Cytochrome P450 2J2	Homo sapiens (human)
regulation of heart contraction	Cytochrome P450 2J2	Homo sapiens (human)
epoxygenase P450 pathway	Cytochrome P450 2J2	Homo sapiens (human)
linoleic acid metabolic process	Cytochrome P450 2J2	Homo sapiens (human)
organic acid metabolic process	Cytochrome P450 2J2	Homo sapiens (human)
xenobiotic metabolic process	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
xenobiotic transmembrane transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
negative regulation of gene expression	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
bile acid and bile salt transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
bilirubin transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
heme catabolic process	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
xenobiotic export from cell	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
transmembrane transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
transepithelial transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
leukotriene transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
monoatomic anion transmembrane transport	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
transport across blood-brain barrier	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
xenobiotic transport across blood-brain barrier	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
ATP binding	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ABC-type xenobiotic transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
glucuronoside transmembrane transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ABC-type bile acid transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ATP hydrolysis activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ATPase-coupled transmembrane transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
xenobiotic transmembrane transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
icosanoid transmembrane transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
ABC-type transporter activity	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
guanine nucleotide transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
protein binding	Multidrug resistance-associated protein 4	Homo sapiens (human)
ATP binding	Multidrug resistance-associated protein 4	Homo sapiens (human)
ABC-type xenobiotic transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
prostaglandin transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
urate transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
purine nucleotide transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
ABC-type bile acid transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
efflux transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
15-hydroxyprostaglandin dehydrogenase (NAD+) activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
ATP hydrolysis activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
glutathione transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
ATPase-coupled transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
xenobiotic transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
ABC-type transporter activity	Multidrug resistance-associated protein 4	Homo sapiens (human)
protein binding	Bile salt export pump	Homo sapiens (human)
ATP binding	Bile salt export pump	Homo sapiens (human)
ABC-type xenobiotic transporter activity	Bile salt export pump	Homo sapiens (human)
bile acid transmembrane transporter activity	Bile salt export pump	Homo sapiens (human)
canalicular bile acid transmembrane transporter activity	Bile salt export pump	Homo sapiens (human)
carbohydrate transmembrane transporter activity	Bile salt export pump	Homo sapiens (human)
ABC-type bile acid transporter activity	Bile salt export pump	Homo sapiens (human)
ATP hydrolysis activity	Bile salt export pump	Homo sapiens (human)
amyloid-beta binding	Beta-2 adrenergic receptor	Homo sapiens (human)
beta2-adrenergic receptor activity	Beta-2 adrenergic receptor	Homo sapiens (human)
protein binding	Beta-2 adrenergic receptor	Homo sapiens (human)
adenylate cyclase binding	Beta-2 adrenergic receptor	Homo sapiens (human)
potassium channel regulator activity	Beta-2 adrenergic receptor	Homo sapiens (human)
identical protein binding	Beta-2 adrenergic receptor	Homo sapiens (human)
protein homodimerization activity	Beta-2 adrenergic receptor	Homo sapiens (human)
protein-containing complex binding	Beta-2 adrenergic receptor	Homo sapiens (human)
norepinephrine binding	Beta-2 adrenergic receptor	Homo sapiens (human)
protein binding	ATP-dependent translocase ABCB1	Homo sapiens (human)
ATP binding	ATP-dependent translocase ABCB1	Homo sapiens (human)
ABC-type xenobiotic transporter activity	ATP-dependent translocase ABCB1	Homo sapiens (human)
efflux transmembrane transporter activity	ATP-dependent translocase ABCB1	Homo sapiens (human)
ATP hydrolysis activity	ATP-dependent translocase ABCB1	Homo sapiens (human)
transmembrane transporter activity	ATP-dependent translocase ABCB1	Homo sapiens (human)
ubiquitin protein ligase binding	ATP-dependent translocase ABCB1	Homo sapiens (human)
ATPase-coupled transmembrane transporter activity	ATP-dependent translocase ABCB1	Homo sapiens (human)
xenobiotic transmembrane transporter activity	ATP-dependent translocase ABCB1	Homo sapiens (human)
carboxylic acid transmembrane transporter activity	ATP-dependent translocase ABCB1	Homo sapiens (human)
phosphatidylcholine floppase activity	ATP-dependent translocase ABCB1	Homo sapiens (human)
phosphatidylethanolamine flippase activity	ATP-dependent translocase ABCB1	Homo sapiens (human)
ceramide floppase activity	ATP-dependent translocase ABCB1	Homo sapiens (human)
floppase activity	ATP-dependent translocase ABCB1	Homo sapiens (human)
beta-adrenergic receptor activity	Beta-1 adrenergic receptor	Homo sapiens (human)
beta1-adrenergic receptor activity	Beta-1 adrenergic receptor	Homo sapiens (human)
protein binding	Beta-1 adrenergic receptor	Homo sapiens (human)
PDZ domain binding	Beta-1 adrenergic receptor	Homo sapiens (human)
alpha-2A adrenergic receptor binding	Beta-1 adrenergic receptor	Homo sapiens (human)
protein heterodimerization activity	Beta-1 adrenergic receptor	Homo sapiens (human)
G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential	Beta-1 adrenergic receptor	Homo sapiens (human)
monooxygenase activity	Cytochrome P450 2D6	Homo sapiens (human)
iron ion binding	Cytochrome P450 2D6	Homo sapiens (human)
oxidoreductase activity	Cytochrome P450 2D6	Homo sapiens (human)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen	Cytochrome P450 2D6	Homo sapiens (human)
heme binding	Cytochrome P450 2D6	Homo sapiens (human)
anandamide 8,9 epoxidase activity	Cytochrome P450 2D6	Homo sapiens (human)
anandamide 11,12 epoxidase activity	Cytochrome P450 2D6	Homo sapiens (human)
anandamide 14,15 epoxidase activity	Cytochrome P450 2D6	Homo sapiens (human)
monooxygenase activity	Cytochrome P450 2C9	Homo sapiens (human)
iron ion binding	Cytochrome P450 2C9	Homo sapiens (human)
arachidonic acid epoxygenase activity	Cytochrome P450 2C9	Homo sapiens (human)
steroid hydroxylase activity	Cytochrome P450 2C9	Homo sapiens (human)
arachidonic acid 14,15-epoxygenase activity	Cytochrome P450 2C9	Homo sapiens (human)
arachidonic acid 11,12-epoxygenase activity	Cytochrome P450 2C9	Homo sapiens (human)
oxidoreductase activity	Cytochrome P450 2C9	Homo sapiens (human)
(S)-limonene 6-monooxygenase activity	Cytochrome P450 2C9	Homo sapiens (human)
(S)-limonene 7-monooxygenase activity	Cytochrome P450 2C9	Homo sapiens (human)
caffeine oxidase activity	Cytochrome P450 2C9	Homo sapiens (human)
(R)-limonene 6-monooxygenase activity	Cytochrome P450 2C9	Homo sapiens (human)
aromatase activity	Cytochrome P450 2C9	Homo sapiens (human)
heme binding	Cytochrome P450 2C9	Homo sapiens (human)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen	Cytochrome P450 2C9	Homo sapiens (human)
norepinephrine binding	Beta-3 adrenergic receptor	Homo sapiens (human)
beta-adrenergic receptor activity	Beta-3 adrenergic receptor	Homo sapiens (human)
protein binding	Beta-3 adrenergic receptor	Homo sapiens (human)
beta3-adrenergic receptor activity	Beta-3 adrenergic receptor	Homo sapiens (human)
beta-3 adrenergic receptor binding	Beta-3 adrenergic receptor	Homo sapiens (human)
protein homodimerization activity	Beta-3 adrenergic receptor	Homo sapiens (human)
epinephrine binding	Beta-3 adrenergic receptor	Homo sapiens (human)
monooxygenase activity	Cytochrome P450 2J2	Homo sapiens (human)
iron ion binding	Cytochrome P450 2J2	Homo sapiens (human)
arachidonic acid epoxygenase activity	Cytochrome P450 2J2	Homo sapiens (human)
arachidonic acid 14,15-epoxygenase activity	Cytochrome P450 2J2	Homo sapiens (human)
arachidonic acid 11,12-epoxygenase activity	Cytochrome P450 2J2	Homo sapiens (human)
isomerase activity	Cytochrome P450 2J2	Homo sapiens (human)
linoleic acid epoxygenase activity	Cytochrome P450 2J2	Homo sapiens (human)
hydroperoxy icosatetraenoate isomerase activity	Cytochrome P450 2J2	Homo sapiens (human)
arachidonic acid 5,6-epoxygenase activity	Cytochrome P450 2J2	Homo sapiens (human)
heme binding	Cytochrome P450 2J2	Homo sapiens (human)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen	Cytochrome P450 2J2	Homo sapiens (human)
protein binding	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ATP binding	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
organic anion transmembrane transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ABC-type xenobiotic transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
bilirubin transmembrane transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ATP hydrolysis activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ATPase-coupled transmembrane transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
xenobiotic transmembrane transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
ABC-type transporter activity	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
plasma membrane	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
basal plasma membrane	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
basolateral plasma membrane	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
membrane	ATP-binding cassette sub-family C member 3	Homo sapiens (human)
nucleolus	Multidrug resistance-associated protein 4	Homo sapiens (human)
Golgi apparatus	Multidrug resistance-associated protein 4	Homo sapiens (human)
plasma membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
basolateral plasma membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
apical plasma membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
platelet dense granule membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
external side of apical plasma membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
plasma membrane	Multidrug resistance-associated protein 4	Homo sapiens (human)
basolateral plasma membrane	Bile salt export pump	Homo sapiens (human)
Golgi membrane	Bile salt export pump	Homo sapiens (human)
endosome	Bile salt export pump	Homo sapiens (human)
plasma membrane	Bile salt export pump	Homo sapiens (human)
cell surface	Bile salt export pump	Homo sapiens (human)
apical plasma membrane	Bile salt export pump	Homo sapiens (human)
intercellular canaliculus	Bile salt export pump	Homo sapiens (human)
intracellular canaliculus	Bile salt export pump	Homo sapiens (human)
recycling endosome	Bile salt export pump	Homo sapiens (human)
recycling endosome membrane	Bile salt export pump	Homo sapiens (human)
extracellular exosome	Bile salt export pump	Homo sapiens (human)
membrane	Bile salt export pump	Homo sapiens (human)
nucleus	Beta-2 adrenergic receptor	Homo sapiens (human)
lysosome	Beta-2 adrenergic receptor	Homo sapiens (human)
endosome	Beta-2 adrenergic receptor	Homo sapiens (human)
early endosome	Beta-2 adrenergic receptor	Homo sapiens (human)
Golgi apparatus	Beta-2 adrenergic receptor	Homo sapiens (human)
plasma membrane	Beta-2 adrenergic receptor	Homo sapiens (human)
endosome membrane	Beta-2 adrenergic receptor	Homo sapiens (human)
membrane	Beta-2 adrenergic receptor	Homo sapiens (human)
apical plasma membrane	Beta-2 adrenergic receptor	Homo sapiens (human)
clathrin-coated endocytic vesicle membrane	Beta-2 adrenergic receptor	Homo sapiens (human)
neuronal dense core vesicle	Beta-2 adrenergic receptor	Homo sapiens (human)
receptor complex	Beta-2 adrenergic receptor	Homo sapiens (human)
plasma membrane	Beta-2 adrenergic receptor	Homo sapiens (human)
cytoplasm	ATP-dependent translocase ABCB1	Homo sapiens (human)
plasma membrane	ATP-dependent translocase ABCB1	Homo sapiens (human)
cell surface	ATP-dependent translocase ABCB1	Homo sapiens (human)
membrane	ATP-dependent translocase ABCB1	Homo sapiens (human)
apical plasma membrane	ATP-dependent translocase ABCB1	Homo sapiens (human)
extracellular exosome	ATP-dependent translocase ABCB1	Homo sapiens (human)
external side of apical plasma membrane	ATP-dependent translocase ABCB1	Homo sapiens (human)
plasma membrane	ATP-dependent translocase ABCB1	Homo sapiens (human)
early endosome	Beta-1 adrenergic receptor	Homo sapiens (human)
plasma membrane	Beta-1 adrenergic receptor	Homo sapiens (human)
Schaffer collateral - CA1 synapse	Beta-1 adrenergic receptor	Homo sapiens (human)
neuronal dense core vesicle	Beta-1 adrenergic receptor	Homo sapiens (human)
plasma membrane	Beta-1 adrenergic receptor	Homo sapiens (human)
mitochondrion	Cytochrome P450 2D6	Homo sapiens (human)
endoplasmic reticulum	Cytochrome P450 2D6	Homo sapiens (human)
endoplasmic reticulum membrane	Cytochrome P450 2D6	Homo sapiens (human)
cytoplasm	Cytochrome P450 2D6	Homo sapiens (human)
intracellular membrane-bounded organelle	Cytochrome P450 2D6	Homo sapiens (human)
endoplasmic reticulum membrane	Cytochrome P450 2C9	Homo sapiens (human)
plasma membrane	Cytochrome P450 2C9	Homo sapiens (human)
intracellular membrane-bounded organelle	Cytochrome P450 2C9	Homo sapiens (human)
cytoplasm	Cytochrome P450 2C9	Homo sapiens (human)
intracellular membrane-bounded organelle	Cytochrome P450 2C9	Homo sapiens (human)
plasma membrane	Beta-3 adrenergic receptor	Homo sapiens (human)
receptor complex	Beta-3 adrenergic receptor	Homo sapiens (human)
plasma membrane	Beta-3 adrenergic receptor	Homo sapiens (human)
plasma membrane	Gamma-aminobutyric acid receptor subunit gamma-2	Rattus norvegicus (Norway rat)
endoplasmic reticulum membrane	Cytochrome P450 2J2	Homo sapiens (human)
extracellular exosome	Cytochrome P450 2J2	Homo sapiens (human)
cytoplasm	Cytochrome P450 2J2	Homo sapiens (human)
intracellular membrane-bounded organelle	Cytochrome P450 2J2	Homo sapiens (human)
plasma membrane	Gamma-aminobutyric acid receptor subunit alpha-1	Rattus norvegicus (Norway rat)
plasma membrane	Gamma-aminobutyric acid receptor subunit beta-2	Rattus norvegicus (Norway rat)
plasma membrane	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
cell surface	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
apical plasma membrane	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
intercellular canaliculus	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
apical plasma membrane	Canalicular multispecific organic anion transporter 1	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Assay ID	Title	Year	Journal	Article
AID1223490	Apparent permeability across human differentiated Caco2 cells	2012	Drug metabolism and disposition: the biological fate of chemicals, Feb, Volume: 40, Issue:2	Predicting phenolic acid absorption in Caco-2 cells: a theoretical permeability model and mechanistic study.
AID1381447	Apparent permeability from apical to basolateral side in MDCK cells	2018	Journal of medicinal chemistry, Aug-09, Volume: 61, Issue:15	Identification of Morpholino Thiophenes as Novel Mycobacterium tuberculosis Inhibitors, Targeting QcrB.
AID168349	Stereoselectivity in presence of rat liver microsomes	1988	Journal of medicinal chemistry, Jan, Volume: 31, Issue:1	Chemical aspects of metoprolol metabolism. Asymmetric synthesis and absolute configuration of the 3-[4-(1-hydroxy-2-methoxyethyl)phenoxy]-1-(isopropylamino)-2-propanols , the diastereomeric benzylic hydroxylation metabolites.
AID1079934	Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID1443980	Inhibition of human BSEP expressed in fall armyworm sf9 cell plasma membrane vesicles assessed as reduction in vesicle-associated [3H]-taurocholate transport preincubated for 10 mins prior to ATP addition measured after 15 mins in presence of [3H]-tauroch	2010	Toxicological sciences : an official journal of the Society of Toxicology, Dec, Volume: 118, Issue:2	Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development.
AID1350705	Efflux ratio of apparent permeability in MDCK-MDR1 cells at 5 uM after 90 mins by LC-MS/MS analysis	2018	Journal of medicinal chemistry, Jul-26, Volume: 61, Issue:14	Optimization of Isothiazolo[4,3- b]pyridine-Based Inhibitors of Cyclin G Associated Kinase (GAK) with Broad-Spectrum Antiviral Activity.
AID337884	Displacement of [125I]dihydroalprenolol from beta adrenergic receptor	1993	Journal of natural products, Apr, Volume: 56, Issue:4	The role of receptor binding in drug discovery.
AID1232324	Antagonist activity against beta-1 adrenergic receptor (unknown origin)	2015	Journal of medicinal chemistry, Aug-13, Volume: 58, Issue:15	Volume of Distribution in Drug Design.
AID540219	Volume of distribution at steady state in monkey after iv administration	2005	Journal of pharmaceutical sciences, Jul, Volume: 94, Issue:7	Extrapolation of human pharmacokinetic parameters from rat, dog, and monkey data: Molecular properties associated with extrapolative success or failure.
AID781326	pKa (acid-base dissociation constant) as determined by Avdeef ref: DOI: 10.1002/047145026X	2014	Pharmaceutical research, Apr, Volume: 31, Issue:4	Comparison of the accuracy of experimental and predicted pKa values of basic and acidic compounds.
AID288185	Permeability coefficient through artificial membrane in presence of stirred water layer	2007	Bioorganic & medicinal chemistry, Jun-01, Volume: 15, Issue:11	QSAR study on permeability of hydrophobic compounds with artificial membranes.
AID266009	Antagonist activity at rat beta-1 adrenergic receptor W134A mutant expressed in CHO cells	2006	Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12	Role of Tyr(356(7.43)) and Ser(190(4.57)) in antagonist binding in the rat beta1-adrenergic receptor.
AID26525	Distribution coefficient measured in Octanol/buffer (0.15 M KCl)	1998	Journal of medicinal chemistry, Dec-31, Volume: 41, Issue:27	Evaluation of dynamic polar molecular surface area as predictor of drug absorption: comparison with other computational and experimental predictors.
AID540210	Clearance in human after iv administration	2008	Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7	Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID266008	Antagonist activity at rat beta-1 adrenergic receptor Y356A mutant expressed in CHO cells	2006	Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12	Role of Tyr(356(7.43)) and Ser(190(4.57)) in antagonist binding in the rat beta1-adrenergic receptor.
AID1210071	Inhibition of CYP3A4 in human liver microsomes using testosterone substrate by LC-MS/MS method	2013	Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1	Discovery and characterization of novel, potent, and selective cytochrome P450 2J2 inhibitors.
AID588217	FDA HLAED, serum glutamic pyruvic transaminase (SGPT) increase	2004	Current drug discovery technologies, Dec, Volume: 1, Issue:4	Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID1079944	Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID40537	Selectivity for beta-1 adrenergic receptor	1988	Journal of medicinal chemistry, Nov, Volume: 31, Issue:11	Modeling of beta-adrenoceptors based on molecular electrostatic potential studies of agonists and antagonists.
AID373867	Hepatic clearance in human hepatocytes in absence of fetal calf serum	2009	European journal of medicinal chemistry, Apr, Volume: 44, Issue:4	First-principle, structure-based prediction of hepatic metabolic clearance values in human.
AID1603578	Displacement of [3H]CGP12177 from mouse beta1 adrenoceptor expressed in HEK293T cell membranes
AID156089	Binding to POPC (palmitoyl-oleolyl-phosphatidyl-choline) liposomes using biosensor system	2000	Journal of medicinal chemistry, Jun-01, Volume: 43, Issue:11	SPR biosensor studies of the direct interaction between 27 drugs and a liposome surface: correlation with fraction absorbed in humans.
AID1079947	Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID1079938	Chronic liver disease either proven histopathologically, or through a chonic elevation of serum amino-transferase activity after 6 months. Value is number of references indexed. [column 'CHRON' in source]
AID588218	FDA HLAED, lactate dehydrogenase (LDH) increase	2004	Current drug discovery technologies, Dec, Volume: 1, Issue:4	Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID444054	Oral bioavailability in human	2010	Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3	Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1350707	Apparent permeability cross apical to basolateral side in MDCK-MDR1 cells at 5 uM after 90 mins by LC-MS/MS analysis	2018	Journal of medicinal chemistry, Jul-26, Volume: 61, Issue:14	Optimization of Isothiazolo[4,3- b]pyridine-Based Inhibitors of Cyclin G Associated Kinase (GAK) with Broad-Spectrum Antiviral Activity.
AID312895	Partition coefficient, log P of the compound	2008	Journal of medicinal chemistry, Feb-14, Volume: 51, Issue:3	High-throughput log P determination by ultraperformance liquid chromatography: a convenient tool for medicinal chemists.
AID1210069	Inhibition of human recombinant CYP2J2 assessed as reduction in astemizole O-demethylation by LC-MS/MS method	2013	Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1	Discovery and characterization of novel, potent, and selective cytochrome P450 2J2 inhibitors.
AID467611	Dissociation constant, pKa of the compound	2009	European journal of medicinal chemistry, Nov, Volume: 44, Issue:11	Prediction of volume of distribution values in human using immobilized artificial membrane partitioning coefficients, the fraction of compound ionized and plasma protein binding data.
AID1223488	1-Octanol-water distribution coefficient, log D of the compound at pH 7.4	2012	Drug metabolism and disposition: the biological fate of chemicals, Feb, Volume: 40, Issue:2	Predicting phenolic acid absorption in Caco-2 cells: a theoretical permeability model and mechanistic study.
AID28924	Effective permeability (Pe) across a hexadecane membrane (pH 6.8)	2001	Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6	High-throughput permeability pH profile and high-throughput alkane/water log P with artificial membranes.
AID604023	Ratio of total drug level in brain to plasma in Sprague-Dawley rat administered in casettes of 2/3 drugs at 4 hr constant rate intravenous infusions using flow rate of 1 (ml/kg)/hr corresponding to dosage rate of 2 (umol/kg)/hr by LC-MS/MS method	2009	Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20	Structure-brain exposure relationships in rat and human using a novel data set of unbound drug concentrations in brain interstitial and cerebrospinal fluids.
AID28679	Partition coefficient (logD6.8)	2001	Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6	High-throughput permeability pH profile and high-throughput alkane/water log P with artificial membranes.
AID236913	Permeability Coefficient in Caco-2 cell culture model	2005	Journal of medicinal chemistry, Jan-27, Volume: 48, Issue:2	Exploring the role of different drug transport routes in permeability screening.
AID1223489	1-Octanol-water distribution coefficient, log D of the compound at pH 7.4 by shake flask method	2012	Drug metabolism and disposition: the biological fate of chemicals, Feb, Volume: 40, Issue:2	Predicting phenolic acid absorption in Caco-2 cells: a theoretical permeability model and mechanistic study.
AID41890	Tested for intrinsic sympathomimetic activity (ISA); Pure antagonist	1988	Journal of medicinal chemistry, Nov, Volume: 31, Issue:11	Modeling of beta-adrenoceptors based on molecular electrostatic potential studies of agonists and antagonists.
AID1220991	Mean transit time of the compound in healthy Wistar rat perfused liver at 3 mM after 10 mins	2011	Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 39, Issue:4	Hepatic pharmacokinetics of cationic drugs in a high-fat emulsion-induced rat model of nonalcoholic steatohepatitis.
AID7779	Oral bioavailability in human	2002	Journal of medicinal chemistry, Jan-17, Volume: 45, Issue:2	Graphical model for estimating oral bioavailability of drugs in humans and other species from their Caco-2 permeability and in vitro liver enzyme metabolic stability rates.
AID1636440	Drug activation in human Hep3B cells assessed as human CYP2D6-mediated drug metabolism-induced cytotoxicity measured as decrease in cell viability at 300 uM pre-incubated with BSO for 18 hrs followed by incubation with compound for 3 hrs in presence of NA	2016	Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16	Development of a cell viability assay to assess drug metabolite structure-toxicity relationships.
AID1232314	Unbound intrinsic clearance in human	2015	Journal of medicinal chemistry, Aug-13, Volume: 58, Issue:15	Volume of Distribution in Drug Design.
AID26362	Ionization constant (pKa)	2004	Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5	Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
AID1079943	Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID350219	Lipophilicity, log K at pH 2 by by hydrophilic interaction chromatography using 95% acetonitrile as mobile phase	2009	Journal of medicinal chemistry, May-28, Volume: 52, Issue:10	Lipophilicity of basic drugs measured by hydrophilic interaction chromatography.
AID19419	Partition coefficient (logD7.4)	1998	Journal of medicinal chemistry, Mar-26, Volume: 41, Issue:7	Physicochemical high throughput screening: parallel artificial membrane permeation assay in the description of passive absorption processes.
AID699539	Inhibition of human liver OATP1B1 expressed in HEK293 Flp-In cells assessed as reduction in E17-betaG uptake at 20 uM by scintillation counting	2012	Journal of medicinal chemistry, May-24, Volume: 55, Issue:10	Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.
AID699540	Inhibition of human liver OATP1B3 expressed in HEK293 Flp-In cells assessed as reduction in [3H]E17-betaG uptake at 20 uM incubated for 5 mins by scintillation counting	2012	Journal of medicinal chemistry, May-24, Volume: 55, Issue:10	Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.
AID681382	TP_TRANSPORTER: inhibition of Verapamil binding in membranes from Vinblastine-induced Caco-2 cells	1999	The Journal of pharmacology and experimental therapeutics, Jan, Volume: 288, Issue:1	Characterization of binding properties to human P-glycoprotein: development of a [3H]verapamil radioligand-binding assay.
AID19424	Partition coefficient (logD7.4)	2001	Journal of medicinal chemistry, Jul-19, Volume: 44, Issue:15	ElogD(oct): a tool for lipophilicity determination in drug discovery. 2. Basic and neutral compounds.
AID1079945	Animal toxicity known. [column 'TOXIC' in source]
AID1528955	Apparent permeability across absorptive direction in Sprague-Dawley rat ileum at 50 uM measured after 20 mins LC-MS/MS analysis
AID588214	FDA HLAED, liver enzyme composite activity	2004	Current drug discovery technologies, Dec, Volume: 1, Issue:4	Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID1603582	Displacement of [3H]CGP12177 from human beta2 adrenoceptor H2.64C mutant expressed in HEK293T cell membranes
AID1473739	Inhibition of human MRP2 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	2013	Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1	A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID425653	Renal clearance in human	2009	Journal of medicinal chemistry, Aug-13, Volume: 52, Issue:15	Physicochemical determinants of human renal clearance.
AID1221015	Intrinsic elimination clearance in healthy Wistar rat perfused liver assessed per gm of liver at 3 mM after 10 mins	2011	Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 39, Issue:4	Hepatic pharmacokinetics of cationic drugs in a high-fat emulsion-induced rat model of nonalcoholic steatohepatitis.
AID40420	Antagonist activity was determined against beta-1 adrenergic receptor in spontaneously beating rat atria	1987	Journal of medicinal chemistry, Jun, Volume: 30, Issue:6	Synthesis of a series of compounds related to betaxolol, a new beta 1-adrenoceptor antagonist with a pharmacological and pharmacokinetic profile optimized for the treatment of chronic cardiovascular diseases.
AID1647951	prevention of heart failure in verapamil treated zebrafish AB assessed as efficacy on venous congestion at 0.5 ug/ml preincubated for 4.5 hrs followed by verapamil treatment and measured after 30 mins relative to verapamil alone
AID714178	Apparent permeability across human Caco2 cells at 10 uM	2012	European journal of medicinal chemistry, Mar, Volume: 49	Recent advances in hypoxia-inducible factor (HIF)-1 inhibitors.
AID1211790	Permeability in mouse jejunum	2013	Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 41, Issue:3	Significance of peptide transporter 1 in the intestinal permeability of valacyclovir in wild-type and PepT1 knockout mice.
AID444058	Volume of distribution at steady state in human	2010	Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3	Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID311367	Permeability coefficient in human skin	2007	Bioorganic & medicinal chemistry, Nov-15, Volume: 15, Issue:22	Transdermal penetration behaviour of drugs: CART-clustering, QSPR and selection of model compounds.
AID1429859	n-octanol-phosphate buffer distribution coefficient, log D of the compound at pH 7.4 after 90 mins by shake-flask method	2017	European journal of medicinal chemistry, Feb-15, Volume: 127	Crystal structures, binding interactions, and ADME evaluation of brain penetrant N-substituted indazole-5-carboxamides as subnanomolar, selective monoamine oxidase B and dual MAO-A/B inhibitors.
AID425652	Total body clearance in human	2009	Journal of medicinal chemistry, Aug-13, Volume: 52, Issue:15	Physicochemical determinants of human renal clearance.
AID1079940	Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID1079942	Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID288184	Permeability coefficient through artificial membrane in presence of unstirred water layer by PAMPA	2007	Bioorganic & medicinal chemistry, Jun-01, Volume: 15, Issue:11	QSAR study on permeability of hydrophobic compounds with artificial membranes.
AID1473738	Inhibition of human BSEP overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-taurocholate in presence of ATP measured after 15 to 20 mins by membrane vesicle transport assay	2013	Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1	A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID1220999	Permeability surface area product in healthy Wistar rat perfused liver assessed per gm of liver at 3 mM after 10 mins	2011	Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 39, Issue:4	Hepatic pharmacokinetics of cationic drugs in a high-fat emulsion-induced rat model of nonalcoholic steatohepatitis.
AID1210070	Inhibition of CYP2D6 in human liver microsomes using bufuralol substrate by LC-MS/MS method	2013	Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1	Discovery and characterization of novel, potent, and selective cytochrome P450 2J2 inhibitors.
AID540209	Volume of distribution at steady state in human after iv administration	2008	Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7	Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID604024	Unbound brain to plasma concentration ratio in Sprague-Dawley rat administered in casettes of 2/3 drugs at 4 hr constant rate intravenous infusions using flow rate of 1 (ml/kg)/hr corresponding to dosage rate of 2 (umol/kg)/hr	2009	Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20	Structure-brain exposure relationships in rat and human using a novel data set of unbound drug concentrations in brain interstitial and cerebrospinal fluids.
AID1602920	Apparent permeability from basolateral to apical side in human Caco2 cells at 5 uM after 90 mins	2019	Journal of medicinal chemistry, 03-14, Volume: 62, Issue:5	Optimization of Blood-Brain Barrier Permeability with Potent and Selective Human Neuronal Nitric Oxide Synthase Inhibitors Having a 2-Aminopyridine Scaffold.
AID1769838	Permeability of the compound at pH 7.4 incubated for 4 hrs by PAMPA-based UV spectrophotometry	2021	Journal of medicinal chemistry, 08-12, Volume: 64, Issue:15	Discovery, Structure-Activity Relationships, and In Vivo Evaluation of Novel Aryl Amides as Brain Penetrant Adaptor Protein 2-Associated Kinase 1 (AAK1) Inhibitors for the Treatment of Neuropathic Pain.
AID404304	Effect on human MRP2-mediated estradiol-17-beta-glucuronide transport in Sf9 cells inverted membrane vesicles relative to control	2008	Journal of medicinal chemistry, Jun-12, Volume: 51, Issue:11	Prediction and identification of drug interactions with the human ATP-binding cassette transporter multidrug-resistance associated protein 2 (MRP2; ABCC2).
AID604021	Unbound volume of distribution in Sprague-Dawley rat brain measured per gram of brain tissue administered in casettes of 2/3 drugs at 4 hr constant rate intravenous infusions using flow rate of 1 (ml/kg)/hr corresponding to dosage rate of 2 (umol/kg)/hr b	2009	Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20	Structure-brain exposure relationships in rat and human using a novel data set of unbound drug concentrations in brain interstitial and cerebrospinal fluids.
AID1318767	Half life in human	2016	Journal of medicinal chemistry, 10-13, Volume: 59, Issue:19	The "Cyclopropyl Fragment" is a Versatile Player that Frequently Appears in Preclinical/Clinical Drug Molecules.
AID7974	Metabolic stability observed at 30 min after administration in human liver microsomes	2002	Journal of medicinal chemistry, Jan-17, Volume: 45, Issue:2	Graphical model for estimating oral bioavailability of drugs in humans and other species from their Caco-2 permeability and in vitro liver enzyme metabolic stability rates.
AID1210073	Inhibition of CYP2C19 in human liver microsomes using omeprazole substrate by LC-MS/MS method	2013	Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1	Discovery and characterization of novel, potent, and selective cytochrome P450 2J2 inhibitors.
AID588219	FDA HLAED, gamma-glutamyl transferase (GGT) increase	2004	Current drug discovery technologies, Dec, Volume: 1, Issue:4	Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID150736	Fraction of high affinity at binding site of human P-Glycoprotein (P-gp) in two-affinity model	2002	Journal of medicinal chemistry, Dec-19, Volume: 45, Issue:26	Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: explanation of structural variety (hypothesis).
AID588215	FDA HLAED, alkaline phosphatase increase	2004	Current drug discovery technologies, Dec, Volume: 1, Issue:4	Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID1731536	Permeability across basolateral to apical side in MDCK cells at 1 uM after 2 hrs by LC-MS/MS analysis	2021	European journal of medicinal chemistry, Mar-15, Volume: 214	Tetrahydroindazole inhibitors of CDK2/cyclin complexes.
AID25870	Tested for the dissociation constant of the compound	1980	Journal of medicinal chemistry, May, Volume: 23, Issue:5	Accumulation of drugs by guinea pig isolated atria. Quantitative correlations.
AID1079946	Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID625286	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatitis	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID288192	Partition coefficient, log P of the compound	2007	Bioorganic & medicinal chemistry, Jun-01, Volume: 15, Issue:11	QSAR study on permeability of hydrophobic compounds with artificial membranes.
AID1731534	Efflux ratio of apparent permeability across basolateral to apical side over apical to basolateral side in MDCK cells at 1 uM after 2 hrs by LC-MS/MS analysis	2021	European journal of medicinal chemistry, Mar-15, Volume: 214	Tetrahydroindazole inhibitors of CDK2/cyclin complexes.
AID28928	Intrinsic permeability of the compound	2001	Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6	High-throughput permeability pH profile and high-throughput alkane/water log P with artificial membranes.
AID1079932	Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID1647955	prevention of heart failure in verapamil treated zebrafish AB assessed as efficacy on blood flow velocity at 0.5 ug/ml preincubated for 4.5 hrs followed by verapamil treatment and measured after 30 mins relative to verapamil alone
AID1602921	Efflux ratio of apparent permeability in human Caco2 cells at 5 uM after 90 mins	2019	Journal of medicinal chemistry, 03-14, Volume: 62, Issue:5	Optimization of Blood-Brain Barrier Permeability with Potent and Selective Human Neuronal Nitric Oxide Synthase Inhibitors Having a 2-Aminopyridine Scaffold.
AID236916	Percentage of mass balance in hexadecane membranes model	2005	Journal of medicinal chemistry, Jan-27, Volume: 48, Issue:2	Exploring the role of different drug transport routes in permeability screening.
AID1211798	Intrinsic clearance in human using well stirred liver model by LC-MS/MS method	2012	Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 40, Issue:1	Comparison of cryopreserved HepaRG cells with cryopreserved human hepatocytes for prediction of clearance for 26 drugs.
AID29139	Calculated dissociation constant (pKa, calculated with ACD/pKa)	2002	Journal of medicinal chemistry, Dec-19, Volume: 45, Issue:26	Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: explanation of structural variety (hypothesis).
AID1392219	Effective permeability of the compound by PAMPA assay	2018	Journal of medicinal chemistry, 05-24, Volume: 61, Issue:10	N
AID1668034	Antiproliferative activity against human SK-MEL-28 cells assessed as cell growth inhibition incubated for 48 hrs by MTT assay	2020	Bioorganic & medicinal chemistry, 05-01, Volume: 28, Issue:9	Drug repurposing and rediscovery: Design, synthesis and preliminary biological evaluation of 1-arylamino-3-aryloxypropan-2-ols as anti-melanoma agents.
AID1221003	Permeability surface area product in perfused liver of high-fat emulsion-induced nonalcoholic steatohepatitis Wistar rat assessed per gm of liver at 3 mM after 10 mins	2011	Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 39, Issue:4	Hepatic pharmacokinetics of cationic drugs in a high-fat emulsion-induced rat model of nonalcoholic steatohepatitis.
AID241889	Inhibitory activity against recombinant human Cytochrome P450 2D6 (CYP2D6) after incubated for 45 minutes	2005	Bioorganic & medicinal chemistry letters, Sep-01, Volume: 15, Issue:17	A 3D-QSAR model for CYP2D6 inhibition in the aryloxypropanolamine series.
AID444053	Renal clearance in human	2010	Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3	Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID540214	Clearance in rat after iv administration	2005	Journal of pharmaceutical sciences, Jul, Volume: 94, Issue:7	Extrapolation of human pharmacokinetic parameters from rat, dog, and monkey data: Molecular properties associated with extrapolative success or failure.
AID1702304	Aqueous solubility of compound in pH 7.4 PBS buffer at 200 uM
AID1079948	Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID481442	Transcellular permeability at pH 6.5 calculated from in vitro P app values in Caco-2 and/or MDCK cells	2010	Journal of medicinal chemistry, May-13, Volume: 53, Issue:9	How well can the Caco-2/Madin-Darby canine kidney models predict effective human jejunal permeability?
AID588213	Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in non-rodents	2010	Chemical research in toxicology, Jan, Volume: 23, Issue:1	Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID1079941	Liver damage due to vascular disease: peliosis hepatitis, hepatic veno-occlusive disease, Budd-Chiari syndrome. Value is number of references indexed. [column 'VASC' in source]
AID236917	Apparent permeability of the compound was determined inCaco-2 (human colon carcinoma) cells; Activity = Papp 10E-6	2005	Journal of medicinal chemistry, Feb-10, Volume: 48, Issue:3	In silico prediction of membrane permeability from calculated molecular parameters.
AID540217	Volume of distribution at steady state in dog after iv administration	2005	Journal of pharmaceutical sciences, Jul, Volume: 94, Issue:7	Extrapolation of human pharmacokinetic parameters from rat, dog, and monkey data: Molecular properties associated with extrapolative success or failure.
AID29423	HPLC capacity factor (k')	2002	Journal of medicinal chemistry, Jun-20, Volume: 45, Issue:13	Prediction of volume of distribution values in humans for neutral and basic drugs using physicochemical measurements and plasma protein binding data.
AID232998	Degree of Selectivity measured as the antilog of pA2 atria-pA2 trachea	1987	Journal of medicinal chemistry, Jun, Volume: 30, Issue:6	Synthesis of a series of compounds related to betaxolol, a new beta 1-adrenoceptor antagonist with a pharmacological and pharmacokinetic profile optimized for the treatment of chronic cardiovascular diseases.
AID7783	Unbound fraction (plasma)	2004	Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5	Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
AID1220973	Drug distribution in healthy Wistar rat perfused liver assessed as equilibrium amount ratio charactering slow binding process at 3 mM after 10 mins	2011	Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 39, Issue:4	Hepatic pharmacokinetics of cationic drugs in a high-fat emulsion-induced rat model of nonalcoholic steatohepatitis.
AID1739432	Permeability across apical to basolateral side in human Caco-2 cells assessed as luciferase yellow leakage at 10 uM incubated for 2 hrs LC-MS/MS analysis	2020	European journal of medicinal chemistry, Aug-15, Volume: 200	Substituted benzothiophene and benzofuran derivatives as a novel class of bone morphogenetic Protein-2 upregulators: Synthesis, anti-osteoporosis efficacies in ovariectomized rats and a zebrafish model, and ADME properties.
AID540218	Clearance in monkey after iv administration	2005	Journal of pharmaceutical sciences, Jul, Volume: 94, Issue:7	Extrapolation of human pharmacokinetic parameters from rat, dog, and monkey data: Molecular properties associated with extrapolative success or failure.
AID540221	Volume of distribution at steady state in human after iv administration	2005	Journal of pharmaceutical sciences, Jul, Volume: 94, Issue:7	Extrapolation of human pharmacokinetic parameters from rat, dog, and monkey data: Molecular properties associated with extrapolative success or failure.
AID1222793	Dissociation constant, pKa of the compound	2013	Drug metabolism and disposition: the biological fate of chemicals, May, Volume: 41, Issue:5	Which metabolites circulate?
AID540212	Mean residence time in human after iv administration	2008	Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7	Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1272412	Permeability across basolateral to apical side in MDCK cells after 90 mins by LC-MS/MS analysis	2016	European journal of medicinal chemistry, Jan-27, Volume: 108	Combating P-glycoprotein-mediated multidrug resistance with 10-O-phenyl dihydroartemisinin ethers in MCF-7 cells.
AID588211	Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in humans	2010	Chemical research in toxicology, Jan, Volume: 23, Issue:1	Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID1381448	Apparent permeability from basolateral to apical side in MDCK cells	2018	Journal of medicinal chemistry, Aug-09, Volume: 61, Issue:15	Identification of Morpholino Thiophenes as Novel Mycobacterium tuberculosis Inhibitors, Targeting QcrB.
AID190412	Antihypertensive activity expressed as percentage of base-line systolic blood pressure of base-line values in spontaneously hypertensive rats (SHR) was reported after 4 hr	1987	Journal of medicinal chemistry, Jun, Volume: 30, Issue:6	Synthesis of a series of compounds related to betaxolol, a new beta 1-adrenoceptor antagonist with a pharmacological and pharmacokinetic profile optimized for the treatment of chronic cardiovascular diseases.
AID236912	Permeability Coefficient in 2/4/A1 cell model	2005	Journal of medicinal chemistry, Jan-27, Volume: 48, Issue:2	Exploring the role of different drug transport routes in permeability screening.
AID625287	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatomegaly	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID45287	permeability in Caco-2 cells; no	2000	Journal of medicinal chemistry, Apr-06, Volume: 43, Issue:7	Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epidermal growth factor receptor: 4-(phenylamino)quinazoline- and 4-(phenylamino)pyrido[3,2-d]pyrimidine-6-acrylamides bearing additional solubilizing functions.
AID1731532	Apparent permeability across apical to basolateral side in MDCK cells at 1 uM after 2 hrs by LC-MS/MS analysis	2021	European journal of medicinal chemistry, Mar-15, Volume: 214	Tetrahydroindazole inhibitors of CDK2/cyclin complexes.
AID604026	Unbound CSF to plasma concentration ratio in human	2009	Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20	Structure-brain exposure relationships in rat and human using a novel data set of unbound drug concentrations in brain interstitial and cerebrospinal fluids.
AID540211	Fraction unbound in human after iv administration	2008	Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7	Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID625280	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID588216	FDA HLAED, serum glutamic oxaloacetic transaminase (SGOT) increase	2004	Current drug discovery technologies, Dec, Volume: 1, Issue:4	Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID29359	Ionization constant (pKa)	2000	Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13	QSAR model for drug human oral bioavailability.
AID230146	The cardioselectivity ratio was obtained by taking the antilog (pA2 beta1-pA2 beta2)	1986	Journal of medicinal chemistry, Jun, Volume: 29, Issue:6	Beta 1-selective adrenoceptor antagonists: examples of the 2-[4-[3-(substituted amino)-2-hydroxypropoxy]phenyl]imidazole class. 2.
AID592681	Apparent permeability across human Caco2 cell membrane after 2 hrs by LC-MS/MS analysis	2011	Bioorganic & medicinal chemistry, Apr-15, Volume: 19, Issue:8	QSAR-based permeability model for drug-like compounds.
AID1539621	Apparent permeability from apical side to basolateral side in human Caco2 cells at 2 uM incubated for 2 hrs in presence of 10 uM pgp/bcrp inhibitor GF120918 by LC-MS/MS analysis	2019	Journal of medicinal chemistry, 09-12, Volume: 62, Issue:17	Targeting GNE Myopathy: A Dual Prodrug Approach for the Delivery of
AID312896	Partition coefficient, log P by UPLC method	2008	Journal of medicinal chemistry, Feb-14, Volume: 51, Issue:3	High-throughput log P determination by ultraperformance liquid chromatography: a convenient tool for medicinal chemists.
AID455986	Permeability across human Caco-2 cells	2009	Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19	Computational modeling of novel inhibitors targeting the Akt pleckstrin homology domain.
AID444051	Total clearance in human	2010	Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3	Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1731535	Permeability across apical to basolateral side in MDCK cells assessed as drug recovery at 1 uM after 2 hrs by LC-MS/MS analysis	2021	European journal of medicinal chemistry, Mar-15, Volume: 214	Tetrahydroindazole inhibitors of CDK2/cyclin complexes.
AID190410	Antihypertensive activity expressed as percentage of base-line systolic blood pressure of base-line values in spontaneously hypertensive rats (SHR) was reported after 24 hr	1987	Journal of medicinal chemistry, Jun, Volume: 30, Issue:6	Synthesis of a series of compounds related to betaxolol, a new beta 1-adrenoceptor antagonist with a pharmacological and pharmacokinetic profile optimized for the treatment of chronic cardiovascular diseases.
AID568158	Apparent permeability across human Caco2 cells	2011	Bioorganic & medicinal chemistry letters, Feb-15, Volume: 21, Issue:4	Structure and property based design, synthesis and biological evaluation of γ-lactam based HDAC inhibitors.
AID177028	Beta agonist activity against heart rate in rats	1984	Journal of medicinal chemistry, Apr, Volume: 27, Issue:4	Beta 1-selective adrenoceptor antagonists. 3. 4-Azolyl-linked phenoxypropanolamines.
AID444056	Fraction escaping gut-wall elimination in human	2010	Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3	Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1636356	Drug activation in human Hep3B cells assessed as human CYP2C9-mediated drug metabolism-induced cytotoxicity measured as decrease in cell viability at 300 uM pre-incubated with BSO for 18 hrs followed by incubation with compound for 3 hrs in presence of NA	2016	Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16	Development of a cell viability assay to assess drug metabolite structure-toxicity relationships.
AID29811	Oral bioavailability in human	2000	Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13	QSAR model for drug human oral bioavailability.
AID236268	Fraction absorbed in human intestine after oral administration compound was measured	2005	Journal of medicinal chemistry, Jan-27, Volume: 48, Issue:2	Exploring the role of different drug transport routes in permeability screening.
AID1626022	Displacement of [3H]DHA from inactive/G protein-uncoupled human beta2-AR expressed in CHO cell membranes by liquid scintillation counting	2016	Journal of medicinal chemistry, 06-23, Volume: 59, Issue:12	Uncoupling the Structure-Activity Relationships of β2 Adrenergic Receptor Ligands from Membrane Binding.
AID1079935	Cytolytic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is > 5 (see ACUTE). Value is number of references indexed. [column 'CYTOL' in source]
AID29844	Fraction absorbed after oral administration in humans	2001	Journal of medicinal chemistry, Jun-07, Volume: 44, Issue:12	Experimental and computational screening models for the prediction of intestinal drug absorption.
AID1079933	Acute liver toxicity defined via clinical observations and clear clinical-chemistry results: serum ALT or AST activity > 6 N or serum alkaline phosphatases activity > 1.7 N. This category includes cytolytic, choleostatic and mixed liver toxicity. Value is
AID625277	FDA Liver Toxicity Knowledge Base Benchmark Dataset (LTKB-BD) drugs of less concern for DILI	2011	Drug discovery today, Aug, Volume: 16, Issue:15-16	FDA-approved drug labeling for the study of drug-induced liver injury.
AID266010	Antagonist activity at rat beta-1 adrenergic receptor S190A mutant expressed in CHO cells	2006	Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12	Role of Tyr(356(7.43)) and Ser(190(4.57)) in antagonist binding in the rat beta1-adrenergic receptor.
AID1272409	Activity at MDR1 (unknown origin) expressed in MDCK cells assessed as permeability across apical to basolateral after 90 mins by LC-MS/MS analysis	2016	European journal of medicinal chemistry, Jan-27, Volume: 108	Combating P-glycoprotein-mediated multidrug resistance with 10-O-phenyl dihydroartemisinin ethers in MCF-7 cells.
AID1350727	Aqueous solubility in PBS buffer at pH 7.4 at 100 uM after 1 hr by LC-MS/MS analysis	2018	Journal of medicinal chemistry, Jul-26, Volume: 61, Issue:14	Optimization of Isothiazolo[4,3- b]pyridine-Based Inhibitors of Cyclin G Associated Kinase (GAK) with Broad-Spectrum Antiviral Activity.
AID1890421	Aqueous solubility of compound in PBS buffer at pH 7.4 by UV absorbance based analysis	2022	European journal of medicinal chemistry, Apr-05, Volume: 233	Design, synthesis, and behavioral evaluation of dual-acting compounds as phosphodiesterase type 10A (PDE10A) inhibitors and serotonin ligands targeting neuropsychiatric symptoms in dementia.
AID1429860	n-octanol-phosphate buffer distribution coefficient, log D of the compound at pH 5.5 after 90 mins by shake-flask method	2017	European journal of medicinal chemistry, Feb-15, Volume: 127	Crystal structures, binding interactions, and ADME evaluation of brain penetrant N-substituted indazole-5-carboxamides as subnanomolar, selective monoamine oxidase B and dual MAO-A/B inhibitors.
AID540230	Dose normalised AUC in rat after po administration	2005	Xenobiotica; the fate of foreign compounds in biological systems, Feb, Volume: 35, Issue:2	Comparative evaluation of oral systemic exposure of 56 xenobiotics in rat, dog, monkey and human.
AID45286	Secretory Transport in Caco-2 cells in comparison to metoprolol	2000	Journal of medicinal chemistry, Apr-06, Volume: 43, Issue:7	Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epidermal growth factor receptor: 4-(phenylamino)quinazoline- and 4-(phenylamino)pyrido[3,2-d]pyrimidine-6-acrylamides bearing additional solubilizing functions.
AID476929	Human intestinal absorption in po dosed human	2010	European journal of medicinal chemistry, Mar, Volume: 45, Issue:3	Neural computational prediction of oral drug absorption based on CODES 2D descriptors.
AID481441	Aqueous diffusivity at 37C	2010	Journal of medicinal chemistry, May-13, Volume: 53, Issue:9	How well can the Caco-2/Madin-Darby canine kidney models predict effective human jejunal permeability?
AID350220	Lipophilicity, log K at pH 2 by by hydrophilic interaction chromatography using 100% water as mobile phase	2009	Journal of medicinal chemistry, May-28, Volume: 52, Issue:10	Lipophilicity of basic drugs measured by hydrophilic interaction chromatography.
AID19006	Calculated membrane partition coefficient (Kmemb)	2004	Journal of medicinal chemistry, Mar-25, Volume: 47, Issue:7	Surface activity profiling of drugs applied to the prediction of blood-brain barrier permeability.
AID41487	Selectivity towards beta-2 adrenergic receptor; Nonselective towards beta-2 adrenergic receptor	1988	Journal of medicinal chemistry, Nov, Volume: 31, Issue:11	Modeling of beta-adrenoceptors based on molecular electrostatic potential studies of agonists and antagonists.
AID625279	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for bilirubinemia	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1220983	Extraction ratio of the compound in healthy Wistar rat perfused liver at 3 mM after 10 mins	2011	Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 39, Issue:4	Hepatic pharmacokinetics of cationic drugs in a high-fat emulsion-induced rat model of nonalcoholic steatohepatitis.
AID540232	Dose normalised AUC in monkey after po administration	2005	Xenobiotica; the fate of foreign compounds in biological systems, Feb, Volume: 35, Issue:2	Comparative evaluation of oral systemic exposure of 56 xenobiotics in rat, dog, monkey and human.
AID28235	Unbound fraction (plasma)	2002	Journal of medicinal chemistry, Jun-20, Volume: 45, Issue:13	Prediction of volume of distribution values in humans for neutral and basic drugs using physicochemical measurements and plasma protein binding data.
AID625290	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver fatty	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079931	Moderate liver toxicity, defined via clinical-chemistry results: ALT or AST serum activity 6 times the normal upper limit (N) or alkaline phosphatase serum activity of 1.7 N. Value is number of references indexed. [column 'BIOL' in source]
AID26304	Partition coefficient (logD6.5)	2000	Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13	QSAR model for drug human oral bioavailability.
AID28926	Effective permeability corrected for ionization	2001	Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6	High-throughput permeability pH profile and high-throughput alkane/water log P with artificial membranes.
AID40527	Cardioselectivity for the beta-1 adrenergic receptor was determined against isoprenaline (antagonism) in isolated rat atria	1987	Journal of medicinal chemistry, Jun, Volume: 30, Issue:6	Synthesis of a series of compounds related to betaxolol, a new beta 1-adrenoceptor antagonist with a pharmacological and pharmacokinetic profile optimized for the treatment of chronic cardiovascular diseases.
AID1465453	Permeability in MDCK cells	2017	Journal of medicinal chemistry, 10-26, Volume: 60, Issue:20	Discovery of N-(4-(2,4-Difluorophenoxy)-3-(6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenyl)ethanesulfonamide (ABBV-075/Mivebresib), a Potent and Orally Available Bromodomain and Extraterminal Domain (BET) Family Bromodomain Inhibitor.
AID1272414	Efflux ratio of permeability across basolateral to apical side over apical to basolateral side in MDCK cells	2016	European journal of medicinal chemistry, Jan-27, Volume: 108	Combating P-glycoprotein-mediated multidrug resistance with 10-O-phenyl dihydroartemisinin ethers in MCF-7 cells.
AID481446	Effective permeability across human jejunum	2010	Journal of medicinal chemistry, May-13, Volume: 53, Issue:9	How well can the Caco-2/Madin-Darby canine kidney models predict effective human jejunal permeability?
AID1473741	Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay	2013	Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1	A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID7812	In vitro rate of absorption observed as Caco-2 permeability in humans	2002	Journal of medicinal chemistry, Jan-17, Volume: 45, Issue:2	Graphical model for estimating oral bioavailability of drugs in humans and other species from their Caco-2 permeability and in vitro liver enzyme metabolic stability rates.
AID1588919	Apparent permeability in human Caco2 cells by LC analysis	2019	Bioorganic & medicinal chemistry, 09-01, Volume: 27, Issue:17	Design, synthesis and biological evaluation of 3-hydroxyquinazoline-2,4(1H,3H)-diones as dual inhibitors of HIV-1 reverse transcriptase-associated RNase H and integrase.
AID777140	Inhibition of RyR2 R4496C mutant (unknown origin)-mediated store-overload induced calcium release expressed in HEK293 cells after 8 to 10 mins by fura-2/AM dye-based fluorescence assay	2013	Journal of medicinal chemistry, Nov-14, Volume: 56, Issue:21	Novel carvedilol analogues that suppress store-overload-induced Ca2+ release.
AID444052	Hepatic clearance in human	2010	Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3	Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1079937	Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID1079939	Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID1209593	Dissociation constant, pKa of the acidic compound by capillary electrophoresis-mass spectrometry analysis	2011	Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3	Measurement of unbound drug exposure in brain: modeling of pH partitioning explains diverging results between the brain slice and brain homogenate methods.
AID444055	Fraction absorbed in human	2010	Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3	Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID21254	Mono layer permeability of human intestinal Caco-2 cells	1998	Journal of medicinal chemistry, Dec-31, Volume: 41, Issue:27	Evaluation of dynamic polar molecular surface area as predictor of drug absorption: comparison with other computational and experimental predictors.
AID1350706	Apparent permeability cross basolateral to apical side in MDCK-MDR1 cells at 5 uM after 90 mins by LC-MS/MS analysis	2018	Journal of medicinal chemistry, Jul-26, Volume: 61, Issue:14	Optimization of Isothiazolo[4,3- b]pyridine-Based Inhibitors of Cyclin G Associated Kinase (GAK) with Broad-Spectrum Antiviral Activity.
AID588212	Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in rodents	2010	Chemical research in toxicology, Jan, Volume: 23, Issue:1	Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID1211793	Lipophilicity, log P of the compound	2012	Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 40, Issue:1	Comparison of cryopreserved HepaRG cells with cryopreserved human hepatocytes for prediction of clearance for 26 drugs.
AID386623	Inhibition of 4-(4-(dimethylamino)styryl)-N-methylpyridinium uptake at human OCT1 expressed in HEK293 cells at 100 uM by confocal microscopy	2008	Journal of medicinal chemistry, Oct-09, Volume: 51, Issue:19	Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1.
AID150735	High affinity constant at binding site of human P-Glycoprotein (P-gp) in two-affinity model	2002	Journal of medicinal chemistry, Dec-19, Volume: 45, Issue:26	Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: explanation of structural variety (hypothesis).
AID1739430	Apparent permeability across apical to basolateral side in human Caco-2 cells at 10 uM incubated for 2 hrs LC-MS/MS analysis	2020	European journal of medicinal chemistry, Aug-15, Volume: 200	Substituted benzothiophene and benzofuran derivatives as a novel class of bone morphogenetic Protein-2 upregulators: Synthesis, anti-osteoporosis efficacies in ovariectomized rats and a zebrafish model, and ADME properties.
AID45284	Efflux in Caco-2 cells; no	2000	Journal of medicinal chemistry, Apr-06, Volume: 43, Issue:7	Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epidermal growth factor receptor: 4-(phenylamino)quinazoline- and 4-(phenylamino)pyrido[3,2-d]pyrimidine-6-acrylamides bearing additional solubilizing functions.
AID1220995	Mean transit time of the compound in perfused liver of high-fat emulsion-induced nonalcoholic steatohepatitis Wistar rat at 3 mM after 10 mins	2011	Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 39, Issue:4	Hepatic pharmacokinetics of cationic drugs in a high-fat emulsion-induced rat model of nonalcoholic steatohepatitis.
AID178335	Inhibition of isoprenaline induced tachycardia in anaesthetised rats.	1984	Journal of medicinal chemistry, Apr, Volume: 27, Issue:4	Beta 1-selective adrenoceptor antagonists. 3. 4-Azolyl-linked phenoxypropanolamines.
AID1220980	Dissociation constant, pKa of the compound	2011	Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 39, Issue:4	Hepatic pharmacokinetics of cationic drugs in a high-fat emulsion-induced rat model of nonalcoholic steatohepatitis.
AID1573588	Efflux ratio of apparent permeability in human Caco2 cells measured at 90 mins time interval by LC-MS/MS analysis	2018	Journal of medicinal chemistry, 10-25, Volume: 61, Issue:20	Development of Macrocyclic Peptides Containing Epoxyketone with Oral Availability as Proteasome Inhibitors.
AID177029	Beta agonistic activity as the dose required to increase heart rate by 30 beats/min in anesthetized rats upon intravenous administration	1983	Journal of medicinal chemistry, Nov, Volume: 26, Issue:11	beta 1-selective adrenoceptor antagonists. 2. 4-ether-linked phenoxypropanolamines.
AID1731533	Apparent permeability across basolateral to apical side in MDCK cells at 1 uM after 2 hrs by LC-MS/MS analysis	2021	European journal of medicinal chemistry, Mar-15, Volume: 214	Tetrahydroindazole inhibitors of CDK2/cyclin complexes.
AID1211789	Permeability of the compound in human jejunum	2013	Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 41, Issue:3	Significance of peptide transporter 1 in the intestinal permeability of valacyclovir in wild-type and PepT1 knockout mice.
AID1626024	Binding affinity to inactive/G protein-uncoupled human beta2-AR by immobilized artificial membrane HPLC analysis	2016	Journal of medicinal chemistry, 06-23, Volume: 59, Issue:12	Uncoupling the Structure-Activity Relationships of β2 Adrenergic Receptor Ligands from Membrane Binding.
AID395325	Lipophilicity, log P by microemulsion electrokinetic chromatography	2009	Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6	Relationship between brain tissue partitioning and microemulsion retention factors of CNS drugs.
AID588220	Literature-mined public compounds from Kruhlak et al phospholipidosis modelling dataset	2008	Toxicology mechanisms and methods, , Volume: 18, Issue:2-3	Development of a phospholipidosis database and predictive quantitative structure-activity relationship (QSAR) models.
AID1232310	Volume of distribution at steady state in human	2015	Journal of medicinal chemistry, Aug-13, Volume: 58, Issue:15	Volume of Distribution in Drug Design.
AID1272411	Permeability across apical to basolateral side in MDCK cells after 90 mins by LC-MS/MS analysis	2016	European journal of medicinal chemistry, Jan-27, Volume: 108	Combating P-glycoprotein-mediated multidrug resistance with 10-O-phenyl dihydroartemisinin ethers in MCF-7 cells.
AID781328	pKa (acid-base dissociation constant) as determined by Luan ref: Pharm. Res. 2005	2014	Pharmaceutical research, Apr, Volume: 31, Issue:4	Comparison of the accuracy of experimental and predicted pKa values of basic and acidic compounds.
AID1603579	Displacement of [3H]CGP12177 from human beta2 adrenoceptor expressed in CHO cell membranes
AID178339	Beta-1 adrenoceptor blocking activity as the dose required to inhibit 50% of tachycardia in anesthetized rats	1983	Journal of medicinal chemistry, Nov, Volume: 26, Issue:11	beta 1-selective adrenoceptor antagonists. 2. 4-ether-linked phenoxypropanolamines.
AID1668042	Antiproliferative activity against human A375 cells assessed as cell growth inhibition at 100 uM measured after 48 hrs by MTT assay relative to control	2020	Bioorganic & medicinal chemistry, 05-01, Volume: 28, Issue:9	Drug repurposing and rediscovery: Design, synthesis and preliminary biological evaluation of 1-arylamino-3-aryloxypropan-2-ols as anti-melanoma agents.
AID1429861	n-octanol-phosphate buffer distribution coefficient, log D of the compound at pH 2 after 90 mins by shake-flask method	2017	European journal of medicinal chemistry, Feb-15, Volume: 127	Crystal structures, binding interactions, and ADME evaluation of brain penetrant N-substituted indazole-5-carboxamides as subnanomolar, selective monoamine oxidase B and dual MAO-A/B inhibitors.
AID25572	Dissociation constant of the compound	1998	Journal of medicinal chemistry, Dec-31, Volume: 41, Issue:27	Evaluation of dynamic polar molecular surface area as predictor of drug absorption: comparison with other computational and experimental predictors.
AID625288	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for jaundice	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1210074	Inhibition of CYP1A2 in human liver microsomes using phenacetin substrate by LC-MS/MS method	2013	Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1	Discovery and characterization of novel, potent, and selective cytochrome P450 2J2 inhibitors.
AID45282	Absorptive transport in Caco-2 cells in comparison to metoprolol	2000	Journal of medicinal chemistry, Apr-06, Volume: 43, Issue:7	Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epidermal growth factor receptor: 4-(phenylamino)quinazoline- and 4-(phenylamino)pyrido[3,2-d]pyrimidine-6-acrylamides bearing additional solubilizing functions.
AID1603581	Displacement of [3H]CGP12177 from mouse beta1 adrenoceptor I2.64C mutant expressed in HEK293T cell membranes
AID1209581	Fraction unbound in Sprague-Dawley rat brain homogenates at 5 uM by equilibrium dialysis analysis	2011	Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3	Measurement of unbound drug exposure in brain: modeling of pH partitioning explains diverging results between the brain slice and brain homogenate methods.
AID699541	Inhibition of human liver OATP2B1 expressed in HEK293 Flp-In cells assessed as reduction in [3H]E3S uptake at 20 uM incubated for 5 mins by scintillation counting	2012	Journal of medicinal chemistry, May-24, Volume: 55, Issue:10	Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.
AID1091956	Apparent hydrophobicity, log D of the compound in Octanol-buffer	2011	Journal of agricultural and food chemistry, Apr-13, Volume: 59, Issue:7	Importance of physicochemical properties for the design of new pesticides.
AID1064760	Apparent permeability in human Caco2 cells	2014	Journal of natural products, Jan-24, Volume: 77, Issue:1	Permeability and conjugative metabolism of flaxseed lignans by Caco-2 human intestinal cells.
AID178334	Inhibition of isoprenaline induced vasopressor response in anaesthetised rats.	1984	Journal of medicinal chemistry, Apr, Volume: 27, Issue:4	Beta 1-selective adrenoceptor antagonists. 3. 4-Azolyl-linked phenoxypropanolamines.
AID1381449	Efflux ratio of apparent permeability from basolateral to apical side over apical to basolateral side of MDCK cells	2018	Journal of medicinal chemistry, Aug-09, Volume: 61, Issue:15	Identification of Morpholino Thiophenes as Novel Mycobacterium tuberculosis Inhibitors, Targeting QcrB.
AID1221011	Apparent distribution ratio of the compound in perfused liver of high-fat emulsion-induced nonalcoholic steatohepatitis Wistar rat at 3 mM after 10 mins	2011	Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 39, Issue:4	Hepatic pharmacokinetics of cationic drugs in a high-fat emulsion-induced rat model of nonalcoholic steatohepatitis.
AID1862271	Apparent permeability across apical to basolateral side in human Caco-2 cells at 2 uM measured after 2 hrs by LC-MS/MS analysis	2022	European journal of medicinal chemistry, Oct-05, Volume: 240	Design, synthesis, and biological evaluation of novel double-winged galloyl derivatives as HIV-1 RNase H inhibitors.
AID350217	Octanol-water partition coefficient, log P of the cationic form of the compound	2009	Journal of medicinal chemistry, May-28, Volume: 52, Issue:10	Lipophilicity of basic drugs measured by hydrophilic interaction chromatography.
AID40869	In vitro beta-2 adrenergic receptor activity was determined by measuring inhibition of the isoproterenol induced relaxation in isolated guinea pig tracheal chains contracted with PGF2-alpha	1983	Journal of medicinal chemistry, Jul, Volume: 26, Issue:7	Beta 1-selective adrenoceptor antagonists: examples of the 2-[4-[3-(substituted-amino)-2-hydroxypropoxy]phenyl]imidazole class.
AID625292	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) combined score	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID28233	Fraction ionized (pH 7.4)	2002	Journal of medicinal chemistry, Jun-20, Volume: 45, Issue:13	Prediction of volume of distribution values in humans for neutral and basic drugs using physicochemical measurements and plasma protein binding data.
AID1603577	Selectivity index, ratio of Ki for displacement of [3H]CGP12177 from human beta2 adrenoceptor expressed in CHO cell membranes to Ki for displacement of [3H]CGP12177 from mouse beta1 adrenoceptor expressed in HEK293T cell membranes
AID1209582	Unbound volume of distribution in Sprague-Dawley rat brain slices at 100 nM after 5 hrs	2011	Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3	Measurement of unbound drug exposure in brain: modeling of pH partitioning explains diverging results between the brain slice and brain homogenate methods.
AID726910	Apparent permeability across apical to basolateral side in human Caco2/TC7 cells after 2 hrs	2013	Bioorganic & medicinal chemistry letters, Jan-15, Volume: 23, Issue:2	From a cytotoxic agent to the discovery of a novel antimalarial agent.
AID231333	Ratio of [(apical to basal)/(basal to apical)] (Caco-2 cell monolayer)	2001	Journal of medicinal chemistry, Jun-07, Volume: 44, Issue:12	Experimental and computational screening models for the prediction of intestinal drug absorption.
AID467613	Volume of distribution at steady state in human	2009	European journal of medicinal chemistry, Nov, Volume: 44, Issue:11	Prediction of volume of distribution values in human using immobilized artificial membrane partitioning coefficients, the fraction of compound ionized and plasma protein binding data.
AID78477	Ability to bind to guinea pig atrial homogenate	1980	Journal of medicinal chemistry, May, Volume: 23, Issue:5	Accumulation of drugs by guinea pig isolated atria. Quantitative correlations.
AID1091955	Dissociation constant, pKa of the compound at pH 7.3	2011	Journal of agricultural and food chemistry, Apr-13, Volume: 59, Issue:7	Importance of physicochemical properties for the design of new pesticides.
AID236914	Permeability Coefficient in hexadecane membranes model	2005	Journal of medicinal chemistry, Jan-27, Volume: 48, Issue:2	Exploring the role of different drug transport routes in permeability screening.
AID678834	TP_TRANSPORTER: transepithelial transport in Caco-2 cells	2003	Pharmaceutical research, Aug, Volume: 20, Issue:8	pH-dependent bidirectional transport of weakly basic drugs across Caco-2 monolayers: implications for drug-drug interactions.
AID481444	Octanol-water partition coefficient, log P of the compound	2010	Journal of medicinal chemistry, May-13, Volume: 53, Issue:9	How well can the Caco-2/Madin-Darby canine kidney models predict effective human jejunal permeability?
AID150618	Concentration required for 50% inhibition at binding site of human P-Glycoprotein (P-gp) in one-affinity model	2002	Journal of medicinal chemistry, Dec-19, Volume: 45, Issue:26	Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: explanation of structural variety (hypothesis).
AID604025	Unbound CSF to plasma concentration ratio in Sprague-Dawley rat administered in casettes of 2/3 drugs at 4 hr constant rate intravenous infusions using flow rate of 1 (ml/kg)/hr corresponding to dosage rate of 2 (umol/kg)/hr by LC-MS/MS method	2009	Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20	Structure-brain exposure relationships in rat and human using a novel data set of unbound drug concentrations in brain interstitial and cerebrospinal fluids.
AID42214	Compound was tested for its Beta-1 adrenergic receptor antagonistic activity on guinea pig arteria	1982	Journal of medicinal chemistry, Aug, Volume: 25, Issue:8	Use of (S)-(trifloxymethyl)oxirane in the synthesis of a chiral beta-adrenoceptor antagonist, (R)- and (S)-9-[[3-(tert-butylamino)-2-hydroxypropyl]oximino]fluorene.
AID236918	Apparent permeability of the compound was determined in MDCK (madin darby canine kidney) strain I; Activity = Papp 10e-6	2005	Journal of medicinal chemistry, Feb-10, Volume: 48, Issue:3	In silico prediction of membrane permeability from calculated molecular parameters.
AID22293	Delta logD (logD6.5 - logD7.4)	2000	Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13	QSAR model for drug human oral bioavailability.
AID288194	Intrinsic artificial membrane permeability coefficient, log P0 of the compound	2007	Bioorganic & medicinal chemistry, Jun-01, Volume: 15, Issue:11	QSAR study on permeability of hydrophobic compounds with artificial membranes.
AID625289	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver disease	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1220979	Octanol-water apparent partition coefficient, logD of the compound at pH 7.4	2011	Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 39, Issue:4	Hepatic pharmacokinetics of cationic drugs in a high-fat emulsion-induced rat model of nonalcoholic steatohepatitis.
AID91480	Ability to bind to human serum albumin (HSA)	1980	Journal of medicinal chemistry, May, Volume: 23, Issue:5	Accumulation of drugs by guinea pig isolated atria. Quantitative correlations.
AID266007	Antagonist activity at rat beta-1 adrenergic receptor Y356F mutant expressed in CHO cells	2006	Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12	Role of Tyr(356(7.43)) and Ser(190(4.57)) in antagonist binding in the rat beta1-adrenergic receptor.
AID540213	Half life in human after iv administration	2008	Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7	Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1221019	Intrinsic elimination clearance in perfused liver of high-fat emulsion-induced nonalcoholic steatohepatitis Wistar rat assessed per gm of liver at 3 mM after 10 mins	2011	Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 39, Issue:4	Hepatic pharmacokinetics of cationic drugs in a high-fat emulsion-induced rat model of nonalcoholic steatohepatitis.
AID237585	Tested for fraction of oral dose absorbed orally in humans	2005	Journal of medicinal chemistry, May-05, Volume: 48, Issue:9	Calculating virtual log P in the alkane/water system (log P(N)(alk)) and its derived parameters deltalog P(N)(oct-alk) and log D(pH)(alk).
AID338168	Displacement of [125I]dihydroalprenolol from beta adrenergic receptor assessed as specific binding relative to total binding	1993	Journal of natural products, Apr, Volume: 56, Issue:4	The role of receptor binding in drug discovery.
AID444050	Fraction unbound in human plasma	2010	Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3	Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID627924	Apparent permeability across apical to basolateral side of dog MDCK cells at 50 uM measured every 15 mins for 1.5 hrs by LC-MS/MS analysis	2011	Bioorganic & medicinal chemistry letters, Jul-15, Volume: 21, Issue:14	Anti-resorptive activity and pharmacokinetic study of N(1),N(1)-diisopropyl-N(2)-(diphenylphosphoryl)-2-(4-nitrophenyl)acetamidine.
AID453203	Lipophilicity, log D of the compound	2010	Bioorganic & medicinal chemistry letters, Jan-01, Volume: 20, Issue:1	Development of an in silico model for human skin permeation based on a Franz cell skin permeability assay.
AID28234	% absorbed in human GI-tract	2001	Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6	High-throughput permeability pH profile and high-throughput alkane/water log P with artificial membranes.
AID1272413	Activity at MDR1 (unknown origin) expressed in MDCK cells assessed as efflux ratio of permeability across basolateral to apical side over apical to basolateral side	2016	European journal of medicinal chemistry, Jan-27, Volume: 108	Combating P-glycoprotein-mediated multidrug resistance with 10-O-phenyl dihydroartemisinin ethers in MCF-7 cells.
AID71778	Local anesthetic activity against beta-1 adrenoceptor was determined with reference to activity(1) of propranolol (beta blocker)	1987	Journal of medicinal chemistry, Jun, Volume: 30, Issue:6	Synthesis of a series of compounds related to betaxolol, a new beta 1-adrenoceptor antagonist with a pharmacological and pharmacokinetic profile optimized for the treatment of chronic cardiovascular diseases.
AID444057	Fraction escaping hepatic elimination in human	2010	Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3	Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1573587	Apparent permeability from basolateral to apical side in human Caco2 cells measured at 90 mins time interval by LC-MS/MS analysis	2018	Journal of medicinal chemistry, 10-25, Volume: 61, Issue:20	Development of Macrocyclic Peptides Containing Epoxyketone with Oral Availability as Proteasome Inhibitors.
AID1474166	Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index	2016	Drug discovery today, Apr, Volume: 21, Issue:4	DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID625282	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cirrhosis	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID40868	Beta-2 adrenergic receptor antagonistic activity on guinea pig tracheal chains	1982	Journal of medicinal chemistry, Aug, Volume: 25, Issue:8	Use of (S)-(trifloxymethyl)oxirane in the synthesis of a chiral beta-adrenoceptor antagonist, (R)- and (S)-9-[[3-(tert-butylamino)-2-hydroxypropyl]oximino]fluorene.
AID1636357	Drug activation in human Hep3B cells assessed as human CYP3A4-mediated drug metabolism-induced cytotoxicity measured as decrease in cell viability at 300 uM pre-incubated with BSO for 18 hrs followed by incubation with compound for 3 hrs in presence of NA	2016	Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16	Development of a cell viability assay to assess drug metabolite structure-toxicity relationships.
AID1079936	Choleostatic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is < 2 (see ACUTE). Value is number of references indexed. [column 'CHOLE' in source]
AID42210	Cardioselectivity for the beta-1 adrenergic receptor was determined against isoprenaline (antagonism) in isolated guinea pig trachea	1987	Journal of medicinal chemistry, Jun, Volume: 30, Issue:6	Synthesis of a series of compounds related to betaxolol, a new beta 1-adrenoceptor antagonist with a pharmacological and pharmacokinetic profile optimized for the treatment of chronic cardiovascular diseases.
AID1091958	Hydrophobicity, log P of the compound in octanol-water by shaking-flask method	2011	Journal of agricultural and food chemistry, Apr-13, Volume: 59, Issue:7	Importance of physicochemical properties for the design of new pesticides.
AID1210072	Inhibition of CYP2C9 in human liver microsomes using tolbutamide substrate by LC-MS/MS method	2013	Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1	Discovery and characterization of novel, potent, and selective cytochrome P450 2J2 inhibitors.
AID481439	Absolute bioavailability in human	2010	Journal of medicinal chemistry, May-13, Volume: 53, Issue:9	How well can the Caco-2/Madin-Darby canine kidney models predict effective human jejunal permeability?
AID467612	Fraction unbound in human plasma	2009	European journal of medicinal chemistry, Nov, Volume: 44, Issue:11	Prediction of volume of distribution values in human using immobilized artificial membrane partitioning coefficients, the fraction of compound ionized and plasma protein binding data.
AID1211791	Fraction unbound in human hepatocytes	2012	Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 40, Issue:1	Comparison of cryopreserved HepaRG cells with cryopreserved human hepatocytes for prediction of clearance for 26 drugs.
AID205268	Inhibition of binding of Batrachotoxinin [3H]BTX-B to high affinity sites on voltage dependent sodium channels in a vesicular preparation from guinea pig cerebral cortex at 10 uM	1985	Journal of medicinal chemistry, Mar, Volume: 28, Issue:3	[3H]Batrachotoxinin A 20 alpha-benzoate binding to voltage-sensitive sodium channels: a rapid and quantitative assay for local anesthetic activity in a variety of drugs.
AID40870	In vitro inhibitory activity against beta-2 adrenergic receptor was measured by the inhibition of isoproterenol-induced relaxation of PGF2-alpha contracted guinea pig trachea	1986	Journal of medicinal chemistry, Jun, Volume: 29, Issue:6	Beta 1-selective adrenoceptor antagonists: examples of the 2-[4-[3-(substituted amino)-2-hydroxypropoxy]phenyl]imidazole class. 2.
AID1668041	Antiproliferative activity against human SK-MEL-28 cells assessed as cell growth inhibition at 100 uM measured after 48 hrs by MTT assay relative to control	2020	Bioorganic & medicinal chemistry, 05-01, Volume: 28, Issue:9	Drug repurposing and rediscovery: Design, synthesis and preliminary biological evaluation of 1-arylamino-3-aryloxypropan-2-ols as anti-melanoma agents.
AID15120	Percent of the drug absorbed after administration to humans was determined	1999	Journal of medicinal chemistry, May-20, Volume: 42, Issue:10	Molecular hashkeys: a novel method for molecular characterization and its application for predicting important pharmaceutical properties of molecules.
AID266006	Antagonist activity at rat wild type beta-1 adrenergic receptor expressed in CHO cells	2006	Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12	Role of Tyr(356(7.43)) and Ser(190(4.57)) in antagonist binding in the rat beta1-adrenergic receptor.
AID625281	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholelithiasis	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID205269	Inhibition of binding of Batrachotoxinin [3H]BTX-B to high-affinity sites on voltage-dependent sodium channels in a vesicular preparation from guinea pig cerebral cortex at 100 uM	1985	Journal of medicinal chemistry, Mar, Volume: 28, Issue:3	[3H]Batrachotoxinin A 20 alpha-benzoate binding to voltage-sensitive sodium channels: a rapid and quantitative assay for local anesthetic activity in a variety of drugs.
AID1578514	Efflux ratio of apparent permeability in human Caco2 cells incubated for 2 hrs by LC/MS analysis	2020	ACS medicinal chemistry letters, Jan-09, Volume: 11, Issue:1	Class I/IIb-Selective HDAC Inhibitor Exhibits Oral Bioavailability and Therapeutic Efficacy in Acute Myeloid Leukemia.
AID625284	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic failure	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID453204	Permeability in human skin after 48 hrs by Franz cell permeability assay	2010	Bioorganic & medicinal chemistry letters, Jan-01, Volume: 20, Issue:1	Development of an in silico model for human skin permeation based on a Franz cell skin permeability assay.
AID1473740	Inhibition of human MRP3 overexpressed in Sf9 insect cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 10 mins by membrane vesicle transport assay	2013	Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1	A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID8002	Observed volume of distribution	2004	Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5	Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
AID1573586	Apparent permeability from apical to basolateral side in human Caco2 cells measured at 90 mins time interval by LC-MS/MS analysis	2018	Journal of medicinal chemistry, 10-25, Volume: 61, Issue:20	Development of Macrocyclic Peptides Containing Epoxyketone with Oral Availability as Proteasome Inhibitors.
AID1220987	Extraction ratio of the compound in perfused liver of high-fat emulsion-induced nonalcoholic steatohepatitis Wistar rat at 3 mM after 10 mins	2011	Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 39, Issue:4	Hepatic pharmacokinetics of cationic drugs in a high-fat emulsion-induced rat model of nonalcoholic steatohepatitis.
AID540216	Clearance in dog after iv administration	2005	Journal of pharmaceutical sciences, Jul, Volume: 94, Issue:7	Extrapolation of human pharmacokinetic parameters from rat, dog, and monkey data: Molecular properties associated with extrapolative success or failure.
AID23672	Partition coefficient (logP)	1980	Journal of medicinal chemistry, May, Volume: 23, Issue:5	Accumulation of drugs by guinea pig isolated atria. Quantitative correlations.
AID1668035	Antiproliferative activity against human A375 cells assessed as cell growth inhibition incubated for 48 hrs by MTT assay	2020	Bioorganic & medicinal chemistry, 05-01, Volume: 28, Issue:9	Drug repurposing and rediscovery: Design, synthesis and preliminary biological evaluation of 1-arylamino-3-aryloxypropan-2-ols as anti-melanoma agents.
AID625283	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for elevated liver function tests	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID603955	In-vivo blood to lung partition coefficients of the compound, logP(lung) in rat	2008	European journal of medicinal chemistry, Mar, Volume: 43, Issue:3	Air to lung partition coefficients for volatile organic compounds and blood to lung partition coefficients for volatile organic compounds and drugs.
AID20050	Human absorption A (%)	1998	Journal of medicinal chemistry, Mar-26, Volume: 41, Issue:7	Physicochemical high throughput screening: parallel artificial membrane permeation assay in the description of passive absorption processes.
AID1739431	Permeability across apical to basolateral side in human Caco-2 cells assessed as transepithelial electrical resistance at 10 uM incubated for 2 hrs LC-MS/MS analysis	2020	European journal of medicinal chemistry, Aug-15, Volume: 200	Substituted benzothiophene and benzofuran derivatives as a novel class of bone morphogenetic Protein-2 upregulators: Synthesis, anti-osteoporosis efficacies in ovariectomized rats and a zebrafish model, and ADME properties.
AID1739433	Metabolic stability in human liver microsomes assessed as half life at 100 uM measured upto 30 mins	2020	European journal of medicinal chemistry, Aug-15, Volume: 200	Substituted benzothiophene and benzofuran derivatives as a novel class of bone morphogenetic Protein-2 upregulators: Synthesis, anti-osteoporosis efficacies in ovariectomized rats and a zebrafish model, and ADME properties.
AID28236	Unbound fraction (tissues)	2002	Journal of medicinal chemistry, Jun-20, Volume: 45, Issue:13	Prediction of volume of distribution values in humans for neutral and basic drugs using physicochemical measurements and plasma protein binding data.
AID730251	Permeability across human Caco2 cells	2013	Journal of medicinal chemistry, Feb-28, Volume: 56, Issue:4	Inhibitors of human immunodeficiency virus type 1 (HIV-1) attachment. 12. Structure-activity relationships associated with 4-fluoro-6-azaindole derivatives leading to the identification of 1-(4-benzoylpiperazin-1-yl)-2-(4-fluoro-7-[1,2,3]triazol-1-yl-1h-p
AID540220	Clearance in human after iv administration	2005	Journal of pharmaceutical sciences, Jul, Volume: 94, Issue:7	Extrapolation of human pharmacokinetic parameters from rat, dog, and monkey data: Molecular properties associated with extrapolative success or failure.
AID1091957	Apparent permeability of the compound by PAMPA	2011	Journal of agricultural and food chemistry, Apr-13, Volume: 59, Issue:7	Importance of physicochemical properties for the design of new pesticides.
AID41350	Beta-2 adrenergic receptor antagonist activity as the dose required to inhibit 50% of vasopressor response in anesthetized rats	1983	Journal of medicinal chemistry, Nov, Volume: 26, Issue:11	beta 1-selective adrenoceptor antagonists. 2. 4-ether-linked phenoxypropanolamines.
AID625285	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic necrosis	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079949	Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID1211797	Intrinsic clearance in cryopreserved human hepatocytes cells assessed per 10'6 cells by LC-MS/MS method	2012	Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 40, Issue:1	Comparison of cryopreserved HepaRG cells with cryopreserved human hepatocytes for prediction of clearance for 26 drugs.
AID625291	Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver function tests abnormal	2011	PLoS computational biology, Dec, Volume: 7, Issue:12	Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1181758	Effective permeability in Wistar rat small intestine assessed as absorption rate coefficient at 50 uM measured after 5 mins in every 5 min interval up to 30 mins	2014	European journal of medicinal chemistry, Aug-18, Volume: 83	A promising camptothecin derivative: Semisynthesis, antitumor activity and intestinal permeability.
AID350216	Dissociation constant, pKa of the compound	2009	Journal of medicinal chemistry, May-28, Volume: 52, Issue:10	Lipophilicity of basic drugs measured by hydrophilic interaction chromatography.
AID1129361	Unbound fraction in HEK293 cell homogenate at 0.1 uM by equilibrium dialysis based UPLC-MS/MS analysis	2014	Journal of medicinal chemistry, Apr-10, Volume: 57, Issue:7	A high-throughput cell-based method to predict the unbound drug fraction in the brain.
AID1211796	Intrinsic clearance in cryopreserved human HepaRG cells assessed per 10'6 cells by LC-MS/MS method	2012	Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 40, Issue:1	Comparison of cryopreserved HepaRG cells with cryopreserved human hepatocytes for prediction of clearance for 26 drugs.
AID526527	Apparent permeability across human Caco-2 cells	2010	Bioorganic & medicinal chemistry letters, Nov-15, Volume: 20, Issue:22	Property based optimization of δ-lactam HDAC inhibitors for metabolic stability.
AID39943	In vitro inhibitory activity against beta-1 adrenergic receptor measured by inhibition of positive chronotropic effect of isoproterenolin in isolated guinea pig atria	1986	Journal of medicinal chemistry, Jun, Volume: 29, Issue:6	Beta 1-selective adrenoceptor antagonists: examples of the 2-[4-[3-(substituted amino)-2-hydroxypropoxy]phenyl]imidazole class. 2.
AID28392	Apparent permeability coefficient (Papp) (Caco-2 cell monolayer)	2001	Journal of medicinal chemistry, Jun-07, Volume: 44, Issue:12	Experimental and computational screening models for the prediction of intestinal drug absorption.
AID681963	TP_TRANSPORTER: inhibition of cimetidine uptake (Cimetidine: 100 uM, Metoprolol: 1000 uM) in OCT2-expressing mIMCD3 cells	2000	British journal of pharmacology, Sep, Volume: 131, Issue:1	The organic cation transporter OCT2 mediates the uptake of beta-adrenoceptor antagonists across the apical membrane of renal LLC-PK(1) cell monolayers.
AID288193	Flux ionization constant, pKa of the membrane permeability coefficient of the compound	2007	Bioorganic & medicinal chemistry, Jun-01, Volume: 15, Issue:11	QSAR study on permeability of hydrophobic compounds with artificial membranes.
AID1181747	Effective permeability from apical to basolateral side in human Caco2 cells at 50 uM after 15 to 90 mins by HPLC analysis	2014	European journal of medicinal chemistry, Aug-18, Volume: 83	A promising camptothecin derivative: Semisynthesis, antitumor activity and intestinal permeability.
AID679583	TP_TRANSPORTER: inhibition of Digoxin transepithelial transport (basal to apical)(Digoxin: 0.1 uM, Metprolol: 50 uM) in MDR1-expressing LLC-PK1 cells	2002	Life sciences, Feb-15, Volume: 70, Issue:13	Interaction of digoxin with antihypertensive drugs via MDR1.
AID230147	The cardioselectivity ratio was obtained by taking the antilog of (pA2(beta-1)-pA2(beta2))	1983	Journal of medicinal chemistry, Jul, Volume: 26, Issue:7	Beta 1-selective adrenoceptor antagonists: examples of the 2-[4-[3-(substituted-amino)-2-hydroxypropoxy]phenyl]imidazole class.
AID1668033	Antiproliferative activity against human SK-MEL-5 cells assessed as cell growth inhibition incubated for 48 hrs by MTT assay	2020	Bioorganic & medicinal chemistry, 05-01, Volume: 28, Issue:9	Drug repurposing and rediscovery: Design, synthesis and preliminary biological evaluation of 1-arylamino-3-aryloxypropan-2-ols as anti-melanoma agents.
AID604020	Unbound drug concentration in Sprague-Dawley rat plasma administered in casettes of 2/3 drugs at 4 hr constant rate intravenous infusions using flow rate of 1 (ml/kg)/hr corresponding to dosage rate of 2 (umol/kg)/hr by LC-MS/MS method	2009	Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20	Structure-brain exposure relationships in rat and human using a novel data set of unbound drug concentrations in brain interstitial and cerebrospinal fluids.
AID1223491	Apparent permeability across human differentiated Caco2 cells at 500 uM after 1 hr by HPLC-DAD analysis	2012	Drug metabolism and disposition: the biological fate of chemicals, Feb, Volume: 40, Issue:2	Predicting phenolic acid absorption in Caco-2 cells: a theoretical permeability model and mechanistic study.
AID190411	Antihypertensive activity expressed as percentage of base-line systolic blood pressure of base-line values in spontaneously hypertensive rats (SHR) was reported after 2 hr	1987	Journal of medicinal chemistry, Jun, Volume: 30, Issue:6	Synthesis of a series of compounds related to betaxolol, a new beta 1-adrenoceptor antagonist with a pharmacological and pharmacokinetic profile optimized for the treatment of chronic cardiovascular diseases.
AID540231	Dose normalised AUC in dog after po administration	2005	Xenobiotica; the fate of foreign compounds in biological systems, Feb, Volume: 35, Issue:2	Comparative evaluation of oral systemic exposure of 56 xenobiotics in rat, dog, monkey and human.
AID1602919	Apparent permeability from apical to basolateral side in human Caco2 cells at 5 uM after 90 mins	2019	Journal of medicinal chemistry, 03-14, Volume: 62, Issue:5	Optimization of Blood-Brain Barrier Permeability with Potent and Selective Human Neuronal Nitric Oxide Synthase Inhibitors Having a 2-Aminopyridine Scaffold.
AID1211794	Fraction unbound in blood (not specified)	2012	Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 40, Issue:1	Comparison of cryopreserved HepaRG cells with cryopreserved human hepatocytes for prediction of clearance for 26 drugs.
AID28399	Cellular permeability (Pc) (Caco-2 cell monolayer)	2001	Journal of medicinal chemistry, Jun-07, Volume: 44, Issue:12	Experimental and computational screening models for the prediction of intestinal drug absorption.
AID1318766	Antagonist activity at rat beta1 adrenoceptor	2016	Journal of medicinal chemistry, 10-13, Volume: 59, Issue:19	The "Cyclopropyl Fragment" is a Versatile Player that Frequently Appears in Preclinical/Clinical Drug Molecules.
AID1739434	Metabolic stability in human liver microsomes assessed as intrinsic clearance at 100 uM measured per mg protein upto 30 mins	2020	European journal of medicinal chemistry, Aug-15, Volume: 200	Substituted benzothiophene and benzofuran derivatives as a novel class of bone morphogenetic Protein-2 upregulators: Synthesis, anti-osteoporosis efficacies in ovariectomized rats and a zebrafish model, and ADME properties.
AID1474167	Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status	2016	Drug discovery today, Apr, Volume: 21, Issue:4	DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID1220977	Drug distribution in perfused liver of high-fat emulsion-induced nonalcoholic steatohepatitis Wistar rat assessed as equilibrium amount ratio charactering slow binding process at 3 mM after 10 mins	2011	Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 39, Issue:4	Hepatic pharmacokinetics of cationic drugs in a high-fat emulsion-induced rat model of nonalcoholic steatohepatitis.
AID1769837	Permeability of the compound at pH 5.5 incubated for 4 hrs by PAMPA-based UV spectrophotometry	2021	Journal of medicinal chemistry, 08-12, Volume: 64, Issue:15	Discovery, Structure-Activity Relationships, and In Vivo Evaluation of Novel Aryl Amides as Brain Penetrant Adaptor Protein 2-Associated Kinase 1 (AAK1) Inhibitors for the Treatment of Neuropathic Pain.
AID28925	Highest effective permeability across hexadecane membrane (pH 4-8)	2001	Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6	High-throughput permeability pH profile and high-throughput alkane/water log P with artificial membranes.
AID1232312	Clearance in human	2015	Journal of medicinal chemistry, Aug-13, Volume: 58, Issue:15	Volume of Distribution in Drug Design.
AID540215	Volume of distribution at steady state in rat after iv administration	2005	Journal of pharmaceutical sciences, Jul, Volume: 94, Issue:7	Extrapolation of human pharmacokinetic parameters from rat, dog, and monkey data: Molecular properties associated with extrapolative success or failure.
AID1221007	Apparent distribution ratio of the compound in healthy Wistar rat perfused liver at 3 mM after 10 mins	2011	Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 39, Issue:4	Hepatic pharmacokinetics of cationic drugs in a high-fat emulsion-induced rat model of nonalcoholic steatohepatitis.
AID1647953	prevention of heart failure in verapamil treated zebrafish AB assessed as efficacy on cardiac output at 0.5 ug/ml preincubated for 4.5 hrs followed by verapamil treatment and measured after 30 mins relative to verapamil alone
AID1232308	Distribution coefficient, log D of the compound	2015	Journal of medicinal chemistry, Aug-13, Volume: 58, Issue:15	Volume of Distribution in Drug Design.
AID1232313	Elimination half life in human	2015	Journal of medicinal chemistry, Aug-13, Volume: 58, Issue:15	Volume of Distribution in Drug Design.
AID18847	Percent of drug absorbed by human intestine after oral administration	2000	Journal of medicinal chemistry, Oct-05, Volume: 43, Issue:20	Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties.
AID395328	Lipophilicity, log P of the compound	2009	Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6	Relationship between brain tissue partitioning and microemulsion retention factors of CNS drugs.
AID28921	Partition coefficient (logP) (hexadecane)	2001	Journal of medicinal chemistry, Mar-15, Volume: 44, Issue:6	High-throughput permeability pH profile and high-throughput alkane/water log P with artificial membranes.
AID350218	Octanol-water partition coefficient, log PC of the compound	2009	Journal of medicinal chemistry, May-28, Volume: 52, Issue:10	Lipophilicity of basic drugs measured by hydrophilic interaction chromatography.
AID608394	Permeability of the compound at 100 uM after 5 hrs by PAMPA	2011	Bioorganic & medicinal chemistry, Jul-15, Volume: 19, Issue:14	Imidazo[1,2-a]pyridin-3-amines as potential HIV-1 non-nucleoside reverse transcriptase inhibitors.
AID604022	Fraction unbound in Sprague-Dawley rat plasma administered in casettes of 2/3 drugs at 4 hr constant rate intravenous infusions using flow rate of 1 (ml/kg)/hr corresponding to dosage rate of 2 (umol/kg)/hr by LC-MS/MS method	2009	Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20	Structure-brain exposure relationships in rat and human using a novel data set of unbound drug concentrations in brain interstitial and cerebrospinal fluids.
AID205267	Inhibition of binding of Batrachotoxinin [3H]BTX-B to high affinity sites on voltage dependent sodium channels in a vesicular preparation from guinea pig cerebral cortex	1985	Journal of medicinal chemistry, Mar, Volume: 28, Issue:3	[3H]Batrachotoxinin A 20 alpha-benzoate binding to voltage-sensitive sodium channels: a rapid and quantitative assay for local anesthetic activity in a variety of drugs.
AID91481	Binding constant against human serum albumin (HSA)	2001	Journal of medicinal chemistry, Dec-06, Volume: 44, Issue:25	Cheminformatic models to predict binding affinities to human serum albumin.
AID1181757	Effective permeability in Wistar rat small intestine at 50 uM measured after 5 mins in every 5 min interval up to 30 mins	2014	European journal of medicinal chemistry, Aug-18, Volume: 83	A promising camptothecin derivative: Semisynthesis, antitumor activity and intestinal permeability.
AID1272410	Activity at MDR1 (unknown origin) expressed in MDCK cells assessed as permeability across basolateral to apical after 90 mins by LC-MS/MS analysis	2016	European journal of medicinal chemistry, Jan-27, Volume: 108	Combating P-glycoprotein-mediated multidrug resistance with 10-O-phenyl dihydroartemisinin ethers in MCF-7 cells.
AID1211792	Hepatic clearance in human	2012	Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 40, Issue:1	Comparison of cryopreserved HepaRG cells with cryopreserved human hepatocytes for prediction of clearance for 26 drugs.
AID1772562	n-Octanol/PBS buffer distribution coefficient, logD of the compound at pH 7.4	2021	European journal of medicinal chemistry, Nov-05, Volume: 223	Non-carboxylic acid inhibitors of aldose reductase based on N-substituted thiazolidinedione derivatives.
AID4411	Binding affinity of a compound to rat brain 5-hydroxytryptamine 1A (serotonin) receptor assayed by radiolabeled [3H]-8-OH-DPAT ligand displacement	1996	Journal of medicinal chemistry, Jan-05, Volume: 39, Issue:1	Binding of arylpiperazines, (aryloxy)propanolamines, and tetrahydropyridylindoles to the 5-HT1A receptor: contribution of the molecular lipophilicity potential to three-dimensional quantitative structure-affinity relationship models.
AID29337	Ionisation constant (pKa)	2002	Journal of medicinal chemistry, Jun-20, Volume: 45, Issue:13	Prediction of volume of distribution values in humans for neutral and basic drugs using physicochemical measurements and plasma protein binding data.
AID1668032	Antiproliferative activity against human SK-MEL-5 cells assessed as cell growth inhibition at 100 uM incubated for 48 hrs by MTT assay relative to control	2020	Bioorganic & medicinal chemistry, 05-01, Volume: 28, Issue:9	Drug repurposing and rediscovery: Design, synthesis and preliminary biological evaluation of 1-arylamino-3-aryloxypropan-2-ols as anti-melanoma agents.
AID27549	Lipophilicity for the compound was determined	1987	Journal of medicinal chemistry, Jun, Volume: 30, Issue:6	Synthesis of a series of compounds related to betaxolol, a new beta 1-adrenoceptor antagonist with a pharmacological and pharmacokinetic profile optimized for the treatment of chronic cardiovascular diseases.
AID29925	Volume of distribution in man (IV dose)	2002	Journal of medicinal chemistry, Jun-20, Volume: 45, Issue:13	Prediction of volume of distribution values in humans for neutral and basic drugs using physicochemical measurements and plasma protein binding data.
AID1232311	Unbound volume of distribution at steady state in human	2015	Journal of medicinal chemistry, Aug-13, Volume: 58, Issue:15	Volume of Distribution in Drug Design.
AID156203	Binding to POPC/GMI liposomes using biosensor system	2000	Journal of medicinal chemistry, Jun-01, Volume: 43, Issue:11	SPR biosensor studies of the direct interaction between 27 drugs and a liposome surface: correlation with fraction absorbed in humans.
AID540233	Dose normalised AUC in human after po administration	2005	Xenobiotica; the fate of foreign compounds in biological systems, Feb, Volume: 35, Issue:2	Comparative evaluation of oral systemic exposure of 56 xenobiotics in rat, dog, monkey and human.
AID1603580	Displacement of [3H]CGP12177 from human beta1 adrenoceptor expressed in HEK293T cell membranes
AID1211795	Dissociation constant, pKa of the compound	2012	Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 40, Issue:1	Comparison of cryopreserved HepaRG cells with cryopreserved human hepatocytes for prediction of clearance for 26 drugs.
AID42218	In vitro beta-1 adrenergic receptor activity was determined via inhibition of the positive chronotropic actions of isoproterenol in isolated guinea pig atrial preparations	1983	Journal of medicinal chemistry, Jul, Volume: 26, Issue:7	Beta 1-selective adrenoceptor antagonists: examples of the 2-[4-[3-(substituted-amino)-2-hydroxypropoxy]phenyl]imidazole class.
AID1209583	Unbound drug partitioning coefficient, Kp of the compound assessed as ratio of unbound concentration in Sprague-Dawley rat brain to unbound concentration in plasma	2011	Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3	Measurement of unbound drug exposure in brain: modeling of pH partitioning explains diverging results between the brain slice and brain homogenate methods.
AID18849	Estimation of fraction absorbed (Fa) in the human intestine using biosensor technology.	2000	Journal of medicinal chemistry, Jun-01, Volume: 43, Issue:11	SPR biosensor studies of the direct interaction between 27 drugs and a liposome surface: correlation with fraction absorbed in humans.
AID237685	Lipophilicity determined as logarithm of the partition coefficient in the alkane/water system	2005	Journal of medicinal chemistry, May-05, Volume: 48, Issue:9	Calculating virtual log P in the alkane/water system (log P(N)(alk)) and its derived parameters deltalog P(N)(oct-alk) and log D(pH)(alk).
AID1626023	Displacement of [3H]DHA from inactive/G protein-uncoupled human beta2-AR expressed in CHO cell membranes assessed as intrinsic Kd by liquid scintillation counting	2016	Journal of medicinal chemistry, 06-23, Volume: 59, Issue:12	Uncoupling the Structure-Activity Relationships of β2 Adrenergic Receptor Ligands from Membrane Binding.
AID481440	Dissociation constant, pKa of the compound	2010	Journal of medicinal chemistry, May-13, Volume: 53, Issue:9	How well can the Caco-2/Madin-Darby canine kidney models predict effective human jejunal permeability?
AID592684	Apparent permeability of the compound by PAMPA	2011	Journal of medicinal chemistry, Apr-14, Volume: 54, Issue:7	In vitro characterization of human peptide transporter hPEPT1 interactions and passive permeation studies of short cationic antimicrobial peptides.
AID1647949	Prevention of heart failure in verapamil treated zebrafish AB assessed as efficacy on heart dilation at 0.5 ug/ml preincubated for 4.5 hrs followed by verapamil treatment and measured after 30 mins relative to verapamil alone
AID1159607	Screen for inhibitors of RMI FANCM (MM2) intereaction	2016	Journal of biomolecular screening, Jul, Volume: 21, Issue:6	A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
AID1346260	Human beta1-adrenoceptor (Adrenoceptors)	2005	British journal of pharmacology, Feb, Volume: 144, Issue:3	The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors.
AID1346260	Human beta1-adrenoceptor (Adrenoceptors)	1999	The Journal of pharmacology and experimental therapeutics, Aug, Volume: 290, Issue:2	Potent and selective human beta(3)-adrenergic receptor antagonists.
AID1346260	Human beta1-adrenoceptor (Adrenoceptors)	2004	Naunyn-Schmiedeberg's archives of pharmacology, Feb, Volume: 369, Issue:2	Comparative pharmacology of human beta-adrenergic receptor subtypes--characterization of stably transfected receptors in CHO cells.
AID1346260	Human beta1-adrenoceptor (Adrenoceptors)	1999	European journal of pharmacology, Feb-19, Volume: 367, Issue:2-3	LK 204-545, a highly selective beta1-adrenoceptor antagonist at human beta-adrenoceptors.
AID1346250	Human beta2-adrenoceptor (Adrenoceptors)	1999	European journal of pharmacology, Feb-19, Volume: 367, Issue:2-3	LK 204-545, a highly selective beta1-adrenoceptor antagonist at human beta-adrenoceptors.
AID1798580	3H-CGP 12177 Whole Cell Binding Assay from Article 10.1038/sj.bjp.0706048: \\The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors.\\	2005	British journal of pharmacology, Feb, Volume: 144, Issue:3	The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors.
AID1347410	qHTS for inhibitors of adenylyl cyclases using a fission yeast platform: a pilot screen against the NCATS LOPAC library	2019	Cellular signalling, 08, Volume: 60	A fission yeast platform for heterologous expression of mammalian adenylyl cyclases and high throughput screening.
AID1347058	CD47-SIRPalpha protein protein interaction - HTRF assay qHTS validation	2019	PloS one, , Volume: 14, Issue:7	Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347151	Optimization of GU AMC qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay	2020	Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49	Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347059	CD47-SIRPalpha protein protein interaction - Alpha assay qHTS validation	2019	PloS one, , Volume: 14, Issue:7	Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347057	CD47-SIRPalpha protein protein interaction - LANCE assay qHTS validation	2019	PloS one, , Volume: 14, Issue:7	Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347405	qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS LOPAC collection	2020	ACS chemical biology, 07-17, Volume: 15, Issue:7	High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID504836	Inducers of the Endoplasmic Reticulum Stress Response (ERSR) in human glioma: Validation	2002	The Journal of biological chemistry, Apr-19, Volume: 277, Issue:16	Sustained ER Ca2+ depletion suppresses protein synthesis and induces activation-enhanced cell death in mast cells.
AID1347049	Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot screen	2019	Science translational medicine, 07-10, Volume: 11, Issue:500	Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID1347045	Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot counterscreen GloSensor control cell line	2019	Science translational medicine, 07-10, Volume: 11, Issue:500	Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID504810	Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign	2010	Endocrinology, Jul, Volume: 151, Issue:7	A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID1347086	qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal	2020	Antiviral research, 01, Volume: 173	A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID588378	qHTS for Inhibitors of ATXN expression: Validation
AID1347082	qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal	2020	Antiviral research, 01, Volume: 173	A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347050	Natriuretic polypeptide receptor (hNpr2) antagonism - Pilot subtype selectivity assay	2019	Science translational medicine, 07-10, Volume: 11, Issue:500	Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID588349	qHTS for Inhibitors of ATXN expression: Validation of Cytotoxic Assay
AID1508630	Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay	2021	Cell reports, 04-27, Volume: 35, Issue:4	A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347083	qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen	2020	Antiviral research, 01, Volume: 173	A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID504812	Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign	2010	Endocrinology, Jul, Volume: 151, Issue:7	A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	1781 (32.18)	18.7374
1990's	1056 (19.08)	18.2507
2000's	1273 (23.00)	29.6817
2010's	1135 (20.51)	24.3611
2020's	289 (5.22)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	1,743 (29.94%)	5.53%
Trials	0 (0.00%)	5.53%
Reviews	293 (5.03%)	6.00%
Reviews	0 (0.00%)	6.00%
Case Studies	460 (7.90%)	4.05%
Case Studies	0 (0.00%)	4.05%
Observational	12 (0.21%)	0.25%
Observational	0 (0.00%)	0.25%
Other	3,313 (56.91%)	84.16%
Other	10 (100.00%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (242)

Trial Overview

Trial	Phase	Enrollment	Study Type	Start Date	Status
"Effect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion. The MEEffect of METOprolol in CARDioproteCtioN During an Acute Myocardial InfarCtion (METOCARD-CNIC): A Randomized, Controlled Parallel-group, Observer-blinded Clinical Trial [NCT01311700]	Phase 4	221 participants (Actual)	Interventional	2010-11-30	Completed
Evaluation of Efficacy and Safety of Metoprolol XR in Patients Having Heart Failure With Normal Ejection Fraction: A Randomised, Double Blind,Placebo Controlled Trial [NCT03882710]	Phase 2	102 participants (Actual)	Interventional	2010-01-31	Completed
Use of Beta-blockers and Risk of New Onset Diabetes [NCT01587638]		12,336 participants (Actual)	Observational	2009-04-30	Completed
Using Heart Rate Variability to Analyze the Effect of Beta Blockers on Intermediate Risk Patients Undergoing Laparoscopic Surgical Procedures [NCT01330654]		0 participants (Actual)	Interventional	2011-03-31	Withdrawn(stopped due to no patients were enrolled. Study was closed prior to study start.)
Danish Trial of Beta Blocker Treatment After Myocardial Infarction Without Reduced Ejection Fraction (DANBLOCK) [NCT03778554]	Phase 4	2,760 participants (Anticipated)	Interventional	2018-12-17	Recruiting
"Single-center, Randomized, Five-way Crossover Study to Investigate Low-dose Combinations of Caffeine, Efavirenz, Losartan, Omeprazole, Metoprolol, Chlorzoxazone and Midazolam (Basel Cocktail) for Simultaneous Phenotyping of CYP1A2, CYP2B6, CYP2C9, CYP2C1 [NCT01187862]	Phase 1	16 participants (Actual)	Interventional	2010-07-31	Completed
Single-Dose Food In Vivo Bioequivalence Study of Metoprolol Tartrate/Hydrochlorothiazide Tablets (100/50 mg; Mylan) to Lopressor HCT® Tablets (100/50 mg; Novartis) in Healthy Volunteers [NCT00649233]	Phase 1	32 participants (Actual)	Interventional	2003-01-31	Completed
An Open-label, Two-treatment Crossover Pharmacokinetic Interaction Study of Repeated Doses of SAR302503 on Pharmacokinetics of a Single Dose Cocktail of Omeprazole, Metoprolol, and Midazolam Used as Probe Substrates for CYP2C19, CYP2D6 and CYP3A4 Activiti [NCT01585623]	Phase 1	16 participants (Actual)	Interventional	2012-06-30	Completed
N-of-1 Trials for Deprescribing Beta-blockers in HFpEF [NCT04767061]	Phase 4	9 participants (Actual)	Interventional	2021-04-01	Completed
Epidemic Profile of Left Ventricular Diastoic Dysfunction in the Community Elderly and Establishing Prediction Model: the Northern Shanghai Study [NCT03735251]		1,920 participants (Actual)	Observational [Patient Registry]	2014-07-10	Completed
Open-label, Drug Interaction Study of Pyronaridine-artesunate and Metoprolol in Healthy Volunteers and Pyronaridine-artesunate Redosing Study in Healthy Volunteers [NCT01523002]	Phase 1	56 participants (Actual)	Interventional	2012-01-31	Completed
Effect of Coreg CR on BP, Endothelial Function, Exhaled Nitric Oxide, and Nitric Oxide Production and Oxidation [NCT00732511]	Phase 4	40 participants (Anticipated)	Interventional	2008-04-30	Recruiting
Assessment of Metoprolol in the Prevention of Vasovagal Syncope in Aging Subjects [NCT02123056]	Phase 4	52 participants (Actual)	Interventional	2014-10-31	Active, not recruiting
A Prospective, Randomized, Open-Label, Active-Comparator, Blinded-Endpoint, 12-week Forced-Titration Study of the Efficacy and Safety of Nebivolol Verses Metoprolol in Hypertensive Subjects Taking Amlodipine [NCT03635125]	Phase 4	40 participants (Actual)	Interventional	2010-08-30	Completed
Evaluation of Metoprolol Pharmacokinetics in Patients Receiving Hi Flux Hemodialysis [NCT03612180]		8 participants (Actual)	Observational	2018-06-30	Completed
An Open-label, Multi Centre Drug-drug Interaction Trial to Investigate the Effects of Tralokinumab on the Pharmacokinetics of Selected Cytochrome P450 Substrates in Adult Subjects With Moderate-to-severe Atopic Dermatitis [NCT03556592]	Phase 1	40 participants (Actual)	Interventional	2018-08-13	Completed
The Effect of Multiple Doses of BI 187004 on the Single Dose Pharmacokinetics of Cytochrome P450 Substrates (Caffeine, Warfarin, Omeprazole, Metoprolol and Midazolam) and a P-glycoprotein Substrate (Digoxin) Administered Orally in an Open-label, One-seque [NCT02254148]	Phase 1	24 participants (Actual)	Interventional	2014-10-31	Completed
Effect of Beta Blockade on Left Ventricular Remodeling and Function in Moderate to Severe Asymptomatic Aortic Regurgitation [NCT01157572]	Phase 4	75 participants (Actual)	Interventional	2010-08-31	Completed
A Phase III, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Factorial Study of Metoprolol Succinate Extended Release Tablets (TOPROL-XL) Hydrochlorothiazide and Their Combination in Patients With Essential Hypertension. [NCT00642096]	Phase 3	1,900 participants (Anticipated)	Interventional	2003-06-30	Completed
An Open-label, Randomized Study Evaluating the Long-term Effects of Metoprolol (MET) Versus Nebivolol (NEB) as Monotherapy or in Combination With Amlodipine or Hydrochlorothiazide for the Treatment of Patients With Hypertension [NCT00142584]	Phase 3	336 participants (Actual)	Interventional	2005-08-31	Completed
Pharmacokinetic and Pharmacodynamic Effect of LY2189265 on Lisinopril in Subjects With Hypertension and Metoprolol in Healthy Subjects [NCT01324388]	Phase 1	51 participants (Actual)	Interventional	2011-03-31	Completed
Use of Determination of Drug Levels to Optimize Pharmacotherapy of Heart Failure [NCT06035978]	Phase 4	100 participants (Anticipated)	Interventional	2023-11-30	Not yet recruiting
A Study to Evaluate the Co-Administration of MK-4618 With Antihypertensive Agents [NCT01337674]	Phase 1	26 participants (Actual)	Interventional	2011-04-01	Completed
Tolerability of Nebivolol Compared With Metoprolol ER in Patients With Mild to Moderate Hypertension Taking Hydrochlorothiazide (HCTZ) [NCT00547300]	Phase 3	49 participants (Actual)	Interventional	2007-10-31	Terminated
The Effect of Metoprolol on Myocardial Function, Perfusion, Hemodynamics and Heart Failure Symptoms in Patients With Hypertrophic Obstructive Cardiomyopathy. [NCT03532802]	Phase 2	30 participants (Actual)	Interventional	2018-05-01	Completed
INFLAMMATION AND DRUG METABOLISM - Does the Effect of Drugs Decrease When Patients With Type 2 Diabetes Initiate Antidiabetic Treatment? [NCT04504045]	Phase 1	10 participants (Actual)	Interventional	2020-09-01	Terminated(stopped due to Slow recruitment due to COVID-19, the study was stopped when recruited numbers fulfilled the pre-defined lower sample size.)
Heart Rate Controller in Computed Tomography Coronary Angiography: A Randomized Controlled Trial of Metoprolol, Diltiazem and Ivabradine [NCT05261464]	Phase 4	246 participants (Anticipated)	Interventional	2021-01-30	Recruiting
Bariatric Surgery and Pharmacokinetics of Metoprolol: BAR-MEDS Metoprolol [NCT03519906]		12 participants (Anticipated)	Observational	2016-11-02	Recruiting
Acute Management of Paroxysmal Atrial Fibrillation With Beta Blockers Plus Intravenous Flecainide: a Real-world Chios Registry (BETAFLEC-CHIOS) [NCT04991896]		81 participants (Actual)	Observational [Patient Registry]	2020-01-01	Completed
Study of Curative Effect Evaluation of DanLou Tablet on Coronary Artery Disease Not Amenable to Revascularization on the Basis of Western Medicine Therapy [NCT03072082]	Phase 4	440 participants (Anticipated)	Interventional	2017-06-30	Not yet recruiting
Novel Strategy For Perioperative Beta-Blocker Therapy - Pilot Study [NCT02746575]	Phase 4	70 participants (Actual)	Interventional	2015-11-30	Completed
Preemptive Pharmacogenetic- Guided Metoprolol Management for Postoperative Atrial Fibrillation in Cardiac Surgery: The PREEMPTIVE- Pilot Trial [NCT03943927]		107 participants (Actual)	Interventional	2021-03-05	Completed
Beta-blocker Effect on Structural Remodeling and Gene Expression in the Failing Human Heart [NCT01798992]	Phase 4	56 participants (Actual)	Interventional	2000-09-30	Completed
Rate Control in Atrial Fibrillation: A Randomized, Double-Blind, Crossover Comparison of Carvedilol and Metoprolol Tartrate [NCT02251509]	Phase 4	20 participants (Anticipated)	Interventional	2016-12-31	Not yet recruiting
Interstitial Cystitis: Examination of the Central Autonomic Network [NCT03008382]	Phase 4	80 participants (Actual)	Interventional	2017-03-01	Completed
An Investigator-Initiated Prospective Randomized Open-Label Blinded-Endpoint Crossover Trial Comparing the Effect and Safety of Flecainide and Metoprolol Versus Metoprolol Alone to Suppress Ventricular Arrhythmias in Arrhythmic Mitral Valve Prolapse [NCT05631730]	Phase 3	50 participants (Anticipated)	Interventional	2023-01-04	Recruiting
A Phase I/II Evaluation of Bromocriptine, Metoprolol and Tamsulosin Combination Therapy in Eyes With Non-Central Diabetic Macular Edema [NCT03384524]	Phase 1/Phase 2	0 participants (Actual)	Interventional	2018-03-31	Withdrawn(stopped due to withdrawn during planning stages)
Pharmacodynamic Effects, Safety and Tolerability of 0.25 mg, 0.5 mg, 1 mg and 2 mg Cilobradine, Compared to 190 mg Metoprolol Succinate and Placebo, Administered p.o. Once Daily Over 14 Days to Healthy Volunteers in a Randomised, Placebo-controlled, Partl [NCT02264002]	Phase 1	119 participants (Actual)	Interventional	2003-02-28	Completed
The Effect of Metoprolol on Anaesthesia, the Need for Analgesics, and Pain in Breast Cancer Patients [NCT02269696]	Phase 3	0 participants (Actual)	Interventional	2018-03-21	Withdrawn(stopped due to Withdrawn)
Metoprolol to Reduce Perioperative Myocardial Injury [NCT03138603]	Phase 3	170 participants (Actual)	Interventional	2016-12-31	Completed
Effect of BMS-914392 on the Pharmacokinetics of Metoprolol and on Heart Rate After Co-administration of BMS-914392 and Metoprolol in Healthy Subjects [NCT01211821]	Phase 1	18 participants (Actual)	Interventional	2010-09-30	Completed
Multicenter Clinical Study of Therapeutic Effect of Sotalol on Children With Arrhythmia (Paroxysmal Supraventricular Tachycardia, Paroxysmal Atrial Tachycardia, Ventricular Tachycardia, Idiopathic Ventricular Tachycardia, Premature Ventricular Contraction [NCT03895411]	Phase 4	500 participants (Anticipated)	Interventional	2019-08-31	Not yet recruiting
Prevention of Atrial Fibrillation in Patients Undergoing Thoracic Surgery for Lung Cancer [NCT01281787]	Phase 3	320 participants (Actual)	Interventional	2008-04-30	Completed
Improving Outcomes in Atrial Fibrillation Patients Aided by Implantable Cardiac Monitor: Evaluation of Chronic Beta-blocker Use Versus As-needed Pharmacological Rate Control [NCT05745337]	Phase 1	20 participants (Anticipated)	Interventional	2023-02-06	Recruiting
Low Dose EPInephrine to Improve Platelet Reactivity in TICagrelor-treated Subjects: A Proof of Concept Study in Healthy Volunteers (EPITIC) [NCT03441412]	Phase 1	10 participants (Actual)	Interventional	2018-02-28	Completed
Effect of Combined Antihypertensive Therapy on Blood Pressure and Sexual Function in Patients With Essential Hypertension [NCT01238705]	Phase 4	280 participants (Anticipated)	Interventional	2008-04-30	Recruiting
A Multi-Center Study on the Metoprolol Optimal Dosing Pathway of Metoprolol Application in Chinese Patients With Acute Coronary Syndrome [NCT03413410]		1,000 participants (Anticipated)	Interventional	2018-02-01	Recruiting
Rate Control in Atrial Fibrillation II [NCT02695992]	Phase 4	122 participants (Actual)	Interventional	2016-02-29	Completed
A Phase 1, Open-label, Drug-Drug Interaction Study to Investigate the Effect of Rocatinlimab (AMG 451) on the Pharmacokinetics of Multiple CYP450 Substrates in Patients With Moderate to Severe Atopic Dermatitis [NCT05891119]	Early Phase 1	20 participants (Anticipated)	Interventional	2023-06-03	Recruiting
Molecular Mechanisms of Volume Overload-Aim 1(SCCOR in Cardiac Dysfunction and Disease) [NCT01052428]	Phase 2/Phase 3	38 participants (Actual)	Interventional	2004-08-31	Completed
LY377604 + Sibutramine Hydrochloride Monohydrate: A Phase 2 Weight Loss Efficacy Study in Overweight/Obese Men and Women [NCT00993421]	Phase 2	343 participants (Actual)	Interventional	2009-10-31	Terminated(stopped due to Clinical trial terminated due to results from recent nonclinical studies)
A Randomised, Open Label, Parallel Group, Multicentre, Phase IV Study on the Effect of 8 Weeks Succinate Metoprolol (Betaloc ZOK®) (95 - 190 mg) on Heart Rate in the Stable Angina Patients [NCT01213173]	Phase 4	251 participants (Actual)	Interventional	2010-10-31	Completed
Blood Pressure and Weight Trajectory on a Dual Antihypertensive Combination Plus Sibutramine Versus Placebo in Obese Hypertensives [NCT00679653]	Phase 3	171 participants (Actual)	Interventional	2002-02-28	Completed
Beta-Blockade in Chronic Mitral Regurgitation: Moving From the Laboratory Experiment to Clinical Investigation [NCT00700947]	Phase 1	27 participants (Actual)	Interventional	2007-10-31	Terminated(stopped due to Funding terminated)
Effect of Nebivolol on Forearm Vasodilation, Nitric Oxide Bioavailability, and Oxidative Stress in Patients With Stage 1/2 Hypertension [NCT00648895]	Phase 3	12 participants (Actual)	Interventional	2007-11-30	Completed
A Phase 3, Multi-center, Randomized, Double-blind Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy [NCT05767346]	Phase 3	170 participants (Anticipated)	Interventional	2023-06-19	Recruiting
Combined Metoprolol and Remote Ischemic Conditioning in Cardioprotection of Anterior ST-segment Elevation Myocardial Infarction (METRICATION) [NCT03579914]		1,206 participants (Actual)	Interventional	2017-11-28	Completed
Impact of Roux-en-Y Gastric Bypass (RYGB) Bariatric Surgery on System Pharmacology: Single-dose Cross-over Pharmacokinetic Study of Simvastatin and Carvedilol. [NCT04049786]	Phase 4	120 participants (Anticipated)	Interventional	2019-06-01	Enrolling by invitation
Effects of Selective and Nonselective Beta-blockade on Platelet Aggregation in Patients With Acute Coronary Syndrome [NCT02809820]	Phase 4	100 participants (Actual)	Interventional	2016-05-31	Completed
An Open-label, Non-randomized, 2-arm, 2-period Fixed Sequence Phase 1 Study to Evaluate the Potential Inhibition of Nitisinone on Cytochrome P450 2C9, 2D6, and 2E1 and the Organic Anion Transporters OAT1 and OAT3 in Healthy Volunteers [NCT03103568]	Phase 1	36 participants (Actual)	Interventional	2017-03-28	Completed
COMParison of the EffecT of mEdication Therapy: Anticoagulation Versus Anti-platelet Versus Migraine Therapy in Alleviating Migraine With Patent Foramen Ovale [NCT05546320]	Phase 4	1,000 participants (Anticipated)	Interventional	2022-10-15	Recruiting
A Randomized, Open-label, Three-sequence, Three-period Crossover Study to Investigate The Effect of Anplag on the Disposition of Betaloc in Healthy Male Volunteers [NCT02097511]	Phase 1	9 participants (Anticipated)	Interventional	2013-12-31	Completed
Efficacy and Safety of Metoprolol Tartrate Tablets Combined With Chinese Traditional Medicine on Premature Ventricular Complex: a Multicenter, Randomized, Double-blind, Parallel Controlled Clinical Study. [NCT05008250]	Phase 4	584 participants (Actual)	Interventional	2014-01-31	Completed
Cluster and Registry Trial of the Working Group of Heart Failure in Denmark. Are Carvedilol and Metoprolol Succinate Comparable Treatments in Heart Failure Patients With Reduced Ejection Fraction [NCT04996550]		5,600 participants (Anticipated)	Observational [Patient Registry]	2022-01-03	Not yet recruiting
A Two-cohort, Open-label, Fixed-sequence, Two-period, Two-treatment Pharmacokinetic Interaction Study of Repeated Oral Doses of Sotagliflozin on a Single Dose Cocktail of Metoprolol and Midazolam Used as Probe Substrates for CYP2D6 and CYP3A Activities, R [NCT02940379]	Phase 1	24 participants (Actual)	Interventional	2016-10-31	Completed
GCC0766: Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol [NCT00806390]	Phase 4	15 participants (Actual)	Interventional	2008-07-31	Terminated(stopped due to Poor enrollment)
TREatment With Beta-blockers After myOcardial Infarction withOut Reduced Ejection fracTion [NCT03596385]	Phase 4	8,468 participants (Anticipated)	Interventional	2018-10-31	Recruiting
Beta-blockeRs tO patieNts With CHronIc Obstructive puLmonary diseasE [NCT03566667]	Phase 4	1,700 participants (Anticipated)	Interventional	2018-06-12	Recruiting
Metoprolol for the Treatment of Cytokine Release Syndrome in Patients Treated With Chimeric Antigen Receptor T Cells [NCT04082910]	Phase 1/Phase 2	30 participants (Anticipated)	Interventional	2019-09-15	Recruiting
"Cardiac Transfer of SARS-CoV-2 Spike Protein Circulation Techniques - Medicine Induced Hemodialysis on Vaccinated Immune Attacks" [NCT05711810]	Phase 4	1 participants (Actual)	Interventional	2023-01-02	Completed
A Randomised, Single Blind, Multicentre, 9-month, Phase IV Study, Comparing Treatment Guided by Clinical Symptoms and Signs and NT-proBNP vs Treatment Guided by Clinical Symptoms and Signs Alone, in Patients With Heart Failure (HF) and Left Ventricular Sy [NCT00391846]	Phase 4	252 participants (Actual)	Interventional	2006-10-31	Completed
Profiling Study for the Hepatic Cytochrome P450 (CYP) Isozymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A in Healthy Subjects and in Patients With Stage 4 (F4) Liver Fibrosis / Cirrhosis by the Combined Administration of the Probe Substrates (the Cocktail) [NCT05741385]		30 participants (Anticipated)	Interventional	2023-04-25	Recruiting
Association Between Angiotensin Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use and COVID-19 Severity and Mortality Among US Veterans [NCT04467931]		22,213 participants (Actual)	Observational	2020-01-19	Completed
Radiofrequency Ablation of Symptomatic Frequent Ventricular Premature Complexes as a First-line Therapy in Pediatric Population Without Structural Heart Disease [NCT02772354]	Phase 2/Phase 3	124 participants (Anticipated)	Interventional	2016-04-30	Recruiting
Post-Acute Sequelae of Coronavirus-19 (COVID-19) With DysPnEA on ExertIon And Associated TaChycardia TrEatment Study [NCT05096884]	Early Phase 1	20 participants (Anticipated)	Interventional	2022-03-23	Recruiting
Glycemic Effects of Nebivolol Compared With Metoprolol Extended Release and Compared With Hydrochlorothiazide In Hypertensive Patients With Type 2 Diabetes Mellitus: A Pilot Study [NCT00744237]	Phase 4	231 participants (Actual)	Interventional	2008-08-31	Completed
Single-Dose Food In Vivo Bioequivalence Study of Metoprolol Tartrate Tablets (100 mg; Mylan) and Lopressor® (100 mg; Novartis) in Healthy Volunteers [NCT00649116]	Phase 1	20 participants (Actual)	Interventional	2002-12-31	Completed
An Open-Label, Drug-Drug Interaction Study to Examine the Effects of Dupilumab on the Pharmacokinetics of Selected Cytochrome P450 Substrates in Adult Patients With Moderate to Severe Atopic Dermatitis [NCT02647086]	Phase 1	14 participants (Actual)	Interventional	2015-12-31	Completed
Single-Dose Fasting In Vivo Bioequivalence Study of Metoprolol Tartrate/Hydrochlorothiazide Tablets (100/50 mg; Mylan) and Lopressor HCT® Tablets (100/50 mg; Novartis) in Healthy Volunteers [NCT00649688]	Phase 1	32 participants (Actual)	Interventional	2003-01-31	Completed
A Randomized, Double-Blind, Multi-Center Study Comparing the Effects of Carvedilol Phosphate Modified Release Formulation (COREG- MR) With Metoprolol Succinate (TOPROL XL) on the Lipid Profile in Normolipidemic, or Mildly Dyslipidemic Hypertensive Patient [NCT00273052]	Phase 3	514 participants (Actual)	Interventional	2006-01-05	Completed
Impact of Nebivolol on Central Aortic Pressure [NCT01051947]		0 participants (Actual)	Interventional	2009-12-31	Withdrawn(stopped due to Similar study already published)
Efficacy and Safety of Arotinolol Hydrochloride on Morning Blood Pressure and Heart Rate in Patients With Essential Hypertension [NCT02612298]	Phase 4	198 participants (Actual)	Interventional	2015-08-31	Completed
The Effects of Nebivolol on Aortic Impedance Parameters in Type 2 Diabetics [NCT00829296]	Phase 2/Phase 3	70 participants (Actual)	Interventional	2009-01-31	Completed
Beta-adrenoceptor Blockade Prior to Induction of Anesthesia for Improvement of Depressed Autonomic Regulation [NCT00700466]		100 participants (Anticipated)	Observational	2008-03-31	Completed
The Influence of Heart Rate Reduction Upon Central Arterial Pressure in Younger and Older Healthy Individuals [NCT01029223]	Phase 4	42 participants (Anticipated)	Interventional	2008-10-31	Withdrawn
[NCT00497003]	Phase 4	50 participants (Actual)	Interventional	2004-02-29	Completed
[NCT00718406]	Phase 4	0 participants	Interventional		Completed
An Open-Label, Non-Comparative, Multi-Centre Study to Evaluate the Efficacy and Safety of Metoprolol Succinate Prolonged-Release Tablet (Betaloc Zok) in Patients With Mild to Moderate Essential Hypertension [NCT00861016]	Phase 4	310 participants (Actual)	Interventional	2005-10-31	Completed
A Randomized, Double-Blind, Multicenter Study Comparing the Effects of Carvedilol and Metoprolol on Glycemic Control in Hypertensive Patients With Type II Diabetes Mellitus. [NCT00060931]	Phase 4	501 participants (Actual)	Interventional	2001-06-30	Completed
The Influence of Heart Rate Reduction Upon Central Arterial Pressure in Younger and Older Healthy Individuals [NCT00825123]	Phase 4	2 participants (Actual)	Interventional	2008-10-31	Terminated
Einfluss Selektiver I(f)-Blockade Auf Orthostase-Toleranz Und Sympathikusaktivität Bei Gesunden [NCT00865917]	Phase 2	40 participants (Anticipated)	Interventional	2008-11-30	Recruiting
Use of Prophylactic Beta Blockade to Prevent Peri-extubation Cardiac Ischemia and Congestive Heart Failure [NCT00563238]		0 participants (Actual)	Interventional	2007-11-30	Withdrawn
A Phase III, Randomized, Double-Blind, Double Placebo-Controlled, Multicenter, Three Parallel Group Study of Enoximone Plus Extended-Release Metoprolol Succinate in Advanced CHF Subjects Previously Intolerant to Beta-Blocker Treatment [NCT00077948]	Phase 3	175 participants	Interventional	2003-07-31	Terminated
Intravenous Metoprolol Versus Biatrial Pacing in the Prevention of Atrial Fibrillation After Cardiac Surgery [NCT00783900]	Phase 4	316 participants (Actual)	Interventional	2007-01-31	Completed
The Success of Opening Single CTO Lesions to Improve Myocardial Viability Study (SOS-comedy) [NCT02767401]	Phase 4	200 participants (Actual)	Interventional	2015-09-15	Completed
N-of-1 Trials for Deprescribing Beta-blockers in HFpEF [NCT04757584]	Phase 4	9 participants (Actual)	Interventional	2021-04-01	Completed
An Open Label, Randomized, Two-Period, Two-Treatment, Two-Sequence, Crossover, Balanced, Single Dose Oral Bioequivalence Study of Metoprolol Succinate Extended Release Tablets 200 mg of Ipca Laboratories Limited, India and 'Toprol-XL®' (Metoprolol Succina [NCT01884896]	Phase 1	48 participants (Actual)	Interventional	2013-02-28	Completed
An Open Label, Randomized, Two-Period, Two-Treatment, Two-Sequence, Crossover, Balanced, Single Dose Oral Bioequivalence Study of Metoprolol Succinate Extended Release Tablets 200 mg of Ipca Laboratories Limited, India and 'Toprol-XL®' (Metoprolol Succina [NCT01884909]	Phase 1	48 participants (Actual)	Interventional	2013-04-30	Completed
Renal Denervation in Patients After Acute Coronary Syndrome [NCT01901549]	Phase 2	80 participants (Anticipated)	Interventional	2013-06-30	Recruiting
Intravenous Metoprolol Versus Intravenous Amiodarone in the Prevention of Atrial Fibrillation After Cardiac Surgery [NCT00784316]	Phase 4	316 participants (Actual)	Interventional	2007-08-31	Completed
A Phase 1, Open-Label, Single-Sequence Crossover Study in Healthy Subjects to Determine the Effect of Relacorilant on Exposure to Probe Substrates for Cytochrome P450s 3A4, 2C8, 2C9, 2C19, and 2D6 [NCT03457597]	Phase 1	27 participants (Actual)	Interventional	2018-03-06	Completed
Effect of Losartan on Retinal Endothelial Function in Patients With Essential Hypertension [NCT00152633]	Phase 2/Phase 3	0 participants (Actual)	Interventional	2005-09-30	Withdrawn(stopped due to No patient could be recruited.)
A Five-arm, Randomised, Open Label, Multi-centre, Prospective Study to Compare the Efficacy, Safety and Tolerability of Metoprolol XL Plus Amlodipine Combination (Selomax TM) With Metoprolol XL and Amlodipine as Individual Components in Management of Hype [NCT00819104]	Phase 4	402 participants (Actual)	Interventional	2008-11-30	Completed
Collaborative Systematic Overview of Randomised Controlled Trials of Beta-Blockers in the Treatment of Heart Failure [NCT00832442]		18,240 participants (Anticipated)	Observational	2008-08-31	Enrolling by invitation
Sympathetic Nervous System Modulation in Hypertension by Beta-adrenergic Blockade [NCT00491387]	Phase 4	24 participants (Actual)	Interventional	2007-08-31	Terminated(stopped due to Adverse events reported with beta-blockers as primary therapy.)
Telmisartan Effectiveness on Left Ventricular MAss Reduction (TELMAR) as Assessed by MRI, in Patients With Mild to Moderate Hypertension - a Prospective, Randomised, Double-blind Comparison of Telmisartan 80 mg Oral, Once Daily, to Metoprolol Succinate 95 [NCT02242812]	Phase 4	24 participants (Actual)	Interventional	2003-09-30	Terminated
An Open Label, Randomized, Two-Period, Two-Treatment, Two-Sequence, Crossover, Balanced, Single Dose Oral Bioequivalence Study of Metoprolol Succinate Extended Release Tablets 50 mg of Ipca Laboratories Limited, India and 'Toprol-XL®' (Metoprolol Succinat [NCT01884857]	Phase 1	48 participants (Actual)	Interventional	2013-04-30	Completed
A Randomized, Double-Blind, 2-Period Crossover Study to Evaluate the Effect of Single Dose JNJ-54452840 on Pharmacodynamics of Metoprolol Tartrate Immediate-Release in Healthy Subjects [NCT01902550]	Phase 1	0 participants (Actual)	Interventional	2013-07-31	Withdrawn(stopped due to Trial was stopped because study not required for development.)
Protective Effects of Propranolol in Adults Following Major Burn Injury: A Safety and Efficacy Trial [NCT01902810]	Phase 2/Phase 3	47 participants (Actual)	Interventional	2013-07-31	Terminated(stopped due to At the request of the study site, this study has been closed and access to study-related data is unavailable. We are unable to submit the results-data.)
Efficacy and Safety Study of Supramaximal Titrated Inhibition of RAAS in Idiopathic Dilated Cardiomyopathy [NCT01917149]	Phase 4	480 participants (Actual)	Interventional	2005-03-31	Completed
CSP #2026 - Beta Blocker Dialyzability on Cardiovascular Outcomes (BRAVO) [NCT05931276]	Phase 3	2,540 participants (Anticipated)	Interventional	2024-01-01	Not yet recruiting
A Comparison of the Effectiveness of Carvedilol Versus Metoprolol for Atrial Fibrillation Appearing After Off-Pump Coronary Bypass Surgery in the Carvedilol or Metoprolol Post-Revascularization Atrial Fibrillation Controlled Trial (COMPACT) [NCT00198614]		650 participants	Interventional	2005-01-31	Completed
Clopidogrel Or Metoprolol in Myocardial Infarction Trial [NCT00222573]	Phase 4	46,000 participants	Interventional	1999-07-31	Completed
Safety and Efficacy of Propranolol in Severely Burned Children [NCT01957449]	Phase 2/Phase 3	63 participants (Actual)	Interventional	2013-12-31	Terminated(stopped due to At the request of the study site, this study has been closed and access to study-related data is unavailable. We are unable to submit the results-data.)
Efficacy and Safety Comparison of Extended-Release Carvedilol Sulfate and Sustained-release Metoprolol Succinate in Patients With Hypertension [NCT01970059]	Phase 3	302 participants (Anticipated)	Interventional	2013-10-31	Recruiting
Comparison of Normotensive Anesthesia Using a Combination of Metoprolol and Tramadol With Controlled Hypotension Using Remifentanil in Endoscopic Sinus Surgery [NCT02484859]	Phase 4	88 participants (Actual)	Interventional	2015-07-31	Completed
Efficacy and Safety Comparison of Extended-Release Carvedilol Sulfate and Sustained-release Metoprolol Succinate in Patients With Heart Failure [NCT02012075]	Phase 3	316 participants (Anticipated)	Interventional	2013-12-31	Recruiting
A Randomised, Open-label, 4-way Crossover Study in Healthy Subjects to Explore the Performance of IntelliCap® by Comparing Pharmacokinetic Profiles of a Probe Drug. [NCT02025348]	Early Phase 1	20 participants (Actual)	Interventional	2014-01-31	Completed
Randomized Trial Comparing Diltiazem and Metoprolol For Atrial Fibrillation Rate Control [NCT02025465]	Phase 4	150 participants (Anticipated)	Interventional	2013-12-31	Recruiting
Effect of Acupoint Application With Herbal Medicine in Patients With Stable Angina Pectoris: Randomized, Controlled,Double Blind Clinical Study [NCT02029118]	Early Phase 1	200 participants (Actual)	Interventional	2012-10-31	Completed
[NCT00000499]	Phase 2	0 participants	Interventional	1980-09-30	Completed
Clonidine to Prevent Implantable Cardiovertor Defibrillator Firing [NCT00585871]		0 participants (Actual)	Interventional	2006-05-31	Withdrawn(stopped due to could not recruit)
Assessment of the Treatment of the Severely Burned With Anabolic Agents on Clinical Outcomes, Recovery and Rehabilitation [NCT00675714]	Phase 2/Phase 3	1,126 participants (Actual)	Interventional	2004-01-31	Terminated(stopped due to At the request of the study site, this study has been closed and access to study-related data is unavailable. We are unable to submit the results-data.)
Single-Dose Food In Vivo Bioequivalence Study of Metoprolol Tartrate Tablets (25 mg; Mylan) and Lopressor® (50 mg; Novartis) in Healthy Volunteers [NCT00648271]	Phase 1	19 participants (Actual)	Interventional	2002-12-31	Completed
Nebivolol Effect on Nitric Oxide Levels, Blood Pressure, and Renal Function in Kidney Transplant Patients [NCT01157234]	Phase 4	32 participants (Actual)	Interventional	2010-07-31	Completed
Pharmacogenomic Evaluation of Antihypertensive Responses 2 [NCT01203852]	Phase 4	839 participants (Actual)	Interventional	2010-08-31	Completed
Comparative Effects of Nebivolol Versus Metoprolol on Sodium Sensitivity and Renal Sodium Handling in Hypertensive Hispanic Postmenopausal Women [NCT00992056]	Phase 4	24 participants (Actual)	Interventional	2010-12-31	Completed
Pacing and AV Node Ablation Compared to Drug Therapy in Symptomatic Elderly Patients With Atrial Fibrillation Clinical Trial (PACIFIC) - Pilot Study [NCT00589303]	Phase 3	27 participants (Actual)	Interventional	2007-12-31	Terminated(stopped due to Lack of funding)
Efficacy and Safety of Chinese Herbal Medicine Wen Xin Granules for the Treatment of Unstable Angina Pectoris With Yang Deficiency and Blood Stasis Syndrome: Study Protocol for a Randomized Controlled Trial [NCT04661709]	Phase 4	502 participants (Anticipated)	Interventional	2021-03-01	Not yet recruiting
The Effect of Multiple Subcutaneous Doses of Risankizumab on the Single Dose Pharmacokinetics of Cytochrome P450 Substrates (Caffeine, Warfarin, Omeprazole, Metoprolol and Midazolam) Administered Orally in an Open-label, One-sequence Trial in Patients Wit [NCT02772601]	Phase 1	21 participants (Actual)	Interventional	2016-09-15	Completed
Tight Hemodynamic Control in Patients Who Are Chronically on Metoprolol: A Study Comparing the Post Op Continuation of the Preoperative Oral Dose Beta Blockers to Intravenous Esmolol Titrated to a Target Heart Rate (HR) [NCT01404767]	Phase 4	20 participants (Actual)	Interventional	2011-04-30	Terminated(stopped due to Enrollment slow over 2 years a change in the population less on metoprolol than initially anticipated)
An International Randomised Controlled Trial to Establish the Effects of Low-dose rtPA and the Effects of Early Intensive Blood Pressure Lowering in Patients With Acute Ischaemic Stroke [NCT01422616]	Phase 3	4,587 participants (Actual)	Interventional	2012-03-31	Completed
Effects of GSK3640254 on the Single-Dose Pharmacokinetics of Probe Substrates (Caffeine, Metoprolol, Montelukast, Flurbiprofen, Omeprazole, Midazolam, Digoxin, and Pravastatin) in Healthy Subjects [NCT04425902]	Phase 1	20 participants (Actual)	Interventional	2020-12-16	Completed
Beta Blockade in Mitral Regurgitation [NCT00166400]	Phase 4	60 participants (Anticipated)	Interventional	2004-07-31	Completed
Perioperative Ischemic Evaluation Study (POISE) Trial [NCT00182039]	Phase 3	8,351 participants (Actual)	Interventional	2002-10-31	Terminated(stopped due to Please see detailed description for reason why study was terminated.)
The Effect of Metoprolol Succinate on the Cardiac Function of Patients With Thalassemia Cardiomyopathy a Double Blind Randomized Study [NCT01863173]	Phase 2/Phase 3	45 participants (Actual)	Interventional	2012-01-31	Completed
Randomised, Double-blind, Placebo-controlled Clinical Trial to Evaluate the to Assess the Efficacy of Intravenous Metoprolol in Patients With Acute Respiratory Distress Syndrome (ARDS). [NCT05847517]	Phase 3	350 participants (Anticipated)	Interventional	2023-11-30	Not yet recruiting
A Pharmacokinetic and Pharmacodynamic Study Comparing Metoprolol IR and Metoprolol CR/XL Subsequent to Initial Treatment With Intravenous and/or Oral Metoprolol in Patients With Suspected Acut Myocardial Infarction [NCT01523054]	Phase 1	27 participants (Actual)	Interventional	2000-02-29	Completed
Beta-blocker Uptitration in Heart Failure Patients Receiving Cardiac Resynchronization Therapy With Optivol Fluid Status Monitoring System [NCT00433043]	Phase 4	2 participants (Actual)	Interventional	2007-01-31	Terminated(stopped due to Insufficient enrollment)
The Surrogate Marker of Rate Control in Patients With Atrial Fibrillation [NCT04513509]		50 participants (Anticipated)	Interventional	2020-08-07	Not yet recruiting
Comparison the Effects of Nebivolol Versus Metoprolol Succinate on Endothelial Function and Large Artery Stiffness [NCT01248338]	Phase 4	80 participants (Actual)	Interventional	2006-03-31	Completed
Diltiazem vs. Metoprolol in the Acute Management of Atrial Fibrillation in Patients With Heart Failure With Reduced Ejection Fraction [NCT02938260]		48 participants (Actual)	Observational	2016-10-31	Completed
An Investigation Into the Effects of Intravenous Lipid Emulsion (ILE) on the Pharmacokinetic and Pharmacodynamic Properties of Metoprolol. [NCT02924454]	Phase 4	10 participants (Actual)	Interventional	2016-09-30	Completed
A Randomised Trial to Establish the Effects of Early Intensive Blood Pressure Lowering on Death and Disability in Patients With Stroke Due to Acute Intracerebral Haemorrhage [NCT00226096]		404 participants (Actual)	Interventional	2005-11-30	Completed
Comparative Effects of Nebivolol Versus Metoprolol on 24-hour Blood Pressures and Basal Metabolic Rate: An Open-Label Study [NCT00849810]		1 participants (Actual)	Interventional	2009-01-31	Terminated(stopped due to Difficulty with recruiting willing participants.)
Comparative Effect of Nebivolol vs. Metoprolol on Insulin Sensitivity and Fibrinolytic Balance in Metabolic Syndrome [NCT00775671]	Phase 4	46 participants (Actual)	Interventional	2008-10-31	Completed
Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy [NCT04133532]	Phase 4	22 participants (Actual)	Interventional	2020-03-05	Completed
African American Study of Kidney Disease and Hypertension [NCT04364139]	Phase 3	1,094 participants (Actual)	Interventional	1995-02-01	Completed
Effect of Metoprolol Succinate in Cardiac Remodeling Related to Nonalcoholic Cirrhosis. Randomized Study. [NCT01676285]	Phase 3	125 participants (Actual)	Interventional	2012-01-31	Completed
Vacular Structure, Function and Sympathetic Activity in Takotsubo Syndrome [NCT05768542]	Phase 1/Phase 2	31 participants (Actual)	Interventional	2016-04-12	Completed
An Open Label, One-sequence, Parallel Study to Compare the Single Dose Pharmacokinetics of YM178 in Healthy Poor or Extensive Metabolisers for CYP2D6 and to Assess the Effect of Multiple Doses of YM178 on the Metabolism of the Model Substrate Metoprolol [NCT01478490]	Phase 1	28 participants (Actual)	Interventional	2002-09-30	Completed
A Safety, Tolerability and Pharmacokinetics Study of TOPROL-XL® (Metoprolol Succinate) Extended-release Tablets (Metoprolol CR/XL) in Hypertensive Pediatric Subjects: A Multicenter, Open-Label Extension of Protocol 307A [NCT00255502]	Phase 3	100 participants	Interventional	2002-07-31	Completed
"Effects of Beta-Blockade on Cardiovascular Morbidity and Mortality in Elderly Trauma Patients: A Prospective Randomized Clinical Trial" [NCT00302692]	Phase 2	148 participants (Anticipated)	Interventional	2005-12-31	Recruiting
BLOCKade of Calcium Channels and Beta Adrenergic Receptors for the Treatment of Hypertension in Heart Failure With Preserved Ejection Fraction (BLOCK HFpEF) Trial [NCT04434664]	Phase 4	50 participants (Anticipated)	Interventional	2021-05-01	Recruiting
Effect of Nebivolol on Blood Pressure in a Model of Hypertension Sensitive to Potentiation of Nitric Oxide Bioactivity [NCT01044693]		20 participants (Actual)	Interventional	2010-01-31	Completed
A Randomized, Double-blind, Positive-Controlled, Multicenter Study Comparing the Efficacy of Carvedilol Phosphate Modified Release Formulation (COREG MR) and Metoprolol Succinate Extended Release (TOPROL-XL) on the Reduction of Microalbuminuria in Patient [NCT00123903]	Phase 3	1,220 participants	Interventional	2005-07-31	Terminated
Coronary Atherosclerosis T1-Weighted Characterization (CATCH) [NCT03504956]		140 participants (Anticipated)	Interventional	2018-07-30	Recruiting
[NCT00475462]		28 participants (Actual)	Interventional	2001-07-31	Completed
Carvedilol vs.Metoprolol: A Comparison of Effects on Endothelial Function and Oxidative Stress in Response to Acute Hyperglycemia in Patients With Type 2 Diabetes and Hypertension [NCT00642434]	Phase 4	22 participants (Actual)	Interventional	2004-01-31	Completed
Open Label Repeated Dose Study for the Evaluation of Heritability of and Genetic Influences on Drug Pharmacokinetics (TWINS II) [NCT01845194]	Phase 1	117 participants (Actual)	Interventional	2009-12-31	Completed
Nebivolol Vs. Metoprolol: Comparative Effects on Fatigue and Quality of Life [NCT00999102]	Phase 4	37 participants (Actual)	Interventional	2009-10-31	Completed
A Randomized, Open-label Study to Evaluate the Effects on Blood Pressure Control, Pulse Wave Velocity, as Well as Safety and Tolerability of Felodipine Sustained Release, Alone and in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide, in Chin [NCT02336607]		529 participants (Actual)	Interventional	2005-12-31	Completed
Interventional, Open-label, One-sequence Study to Investigate the Effects of Lu AG06466 on the Pharmacokinetics of the Cytochrome P450 Substrates Midazolam (CYP3A4), Bupropion (CYP2B6), and Metoprolol (CYP2D6) in Healthy Young Men and Women [NCT04713254]	Phase 1	15 participants (Actual)	Interventional	2020-12-08	Completed
Effects of Nebivolol on Microvascular Perfusion in the Skeletal Muscles During Exercise in Hypertensive Patients [NCT01501929]	Phase 4	32 participants (Actual)	Interventional	2010-08-31	Completed
Effects of Nebivolol Versus Metoprolol on Blood Flow Responses to Exercise and Angiotensin II in Hypertensive Patients [NCT01502787]	Phase 4	46 participants (Actual)	Interventional	2009-04-30	Completed
Action to Control Cardiovascular Risk in Diabetes (ACCORD) [NCT00000620]	Phase 3	10,251 participants (Actual)	Interventional	1999-09-30	Completed
[NCT00038077]	Phase 3	300 participants	Interventional	2001-08-31	Completed
Randomized Clinical Trial of Ivabradine to Reduce Heart Rate Prior to Coronary CT-angiography in Advanced Heart Failure: Comparison With β-Blocker [NCT03830957]		200 participants (Anticipated)	Interventional	2018-11-26	Recruiting
A Randomized, Double-Blind, Multicenter Study Comparing the Glycemic Control Characteristics of Carvedilol and Metoprolol in Hypertensive Patients With Type II Diabetes Mellitus. [NCT00060918]	Phase 4	1,210 participants	Interventional	2001-06-30	Completed
Clinical Bioequivalence Study on Two Metoprolol Tablet 100mg Formulations [NCT03082352]	Phase 1	30 participants (Anticipated)	Interventional	2020-08-31	Not yet recruiting
The Effects of ß2 Polymorphisms on Beta Selectivity After ß-adrenergic Blockade in Patients With Heart Failure [NCT00214318]		25 participants	Interventional	2005-01-31	Completed
A Comparison of the Effect of Intraoperative Administration of Metoprolol or Esmolol on General Anesthetic Requirement [NCT00756236]		60 participants (Actual)	Interventional	2008-10-31	Completed
The Pathophysiology and Treatment of Supine Hypertension in Patients With Autonomic Failure [NCT00223717]	Phase 1	152 participants (Actual)	Interventional	2001-01-31	Completed
The Efficacy and Safety of Metoprolol as add-on Treatment to Standard of Care in Preventing Cardiomyopathy in Patients With Duchenne Muscular Dystrophy Aged 8-16 Years. A Randomized, Double-blind, Placebo-controlled Study [NCT05066633]	Phase 3	150 participants (Anticipated)	Interventional	2021-08-18	Recruiting
Open-Labeled Pharmacokinetic and Pharmacodynamic (PK-PD) Studies of Metoprolol ER [NCT02417246]	Phase 4	61 participants (Actual)	Interventional	2015-08-31	Completed
Black Education and Treatment of Hypertension (BEAT HTN) [NCT00661895]	Phase 4	99 participants (Actual)	Interventional	2005-08-31	Completed
Optimization of Pre-surgical Testing With an Intensive Multifactorial Intervention to MinimiZe Cardiovascular Events in Orthopedic Surgery [NCT01837069]	Phase 4	198 participants (Actual)	Interventional	2014-02-28	Terminated(stopped due to Low recruitment / DSMB approval to halt recruitment)
Dose Ranging, Safety and Tolerability of TOPROL-XL® (Metoprolol Succinate) Extended-Release Tablets (Metoprolol CR/XL) in Hypertensive Pediatric Subjects: A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Parallel-Group Study [NCT00255528]	Phase 3	144 participants	Interventional	2002-07-31	Completed
Effects of Carvedilol and Metoprolol on Endothelial Function in Hypertensive Patients With Type 2 Diabetes Mellitus [NCT00123604]	Phase 4	36 participants (Actual)	Interventional	2004-06-30	Completed
Pulmonary Effects of the Combination of Metoprolol and Formoterol in COPD [NCT00288548]	Phase 4	45 participants	Interventional	2006-02-28	Recruiting
Rate Control in Atrial Fibrillation [NCT00313157]	Phase 3	80 participants (Actual)	Interventional	2006-04-30	Completed
A Single Center Study of Perivascular Coronary Inflammation in Patients With Myocardial Ischemia or Infarction With Non-Obstructive Coronary Arteries [NCT05031520]		100 participants (Anticipated)	Observational	2021-07-12	Recruiting
Oral Propranolol, Diltiazem, Metoprolol and Verapamil in Atrial Fibrillation Rate Control in Patients With Stable Hemodynamic Status [NCT01655303]	Phase 4	90 participants (Actual)	Interventional	2011-02-28	Completed
A Single-site, Open-label, Fixed-sequence Phase 1 Study Evaluating the Effect of Eliglustat (Genz-112638) on the Pharmacokinetics, Safety and Tolerability of Metoprolol in Healthy Adult Subjects. [NCT01659944]	Phase 1	14 participants (Actual)	Interventional	2012-05-31	Completed
An Open Label, Balanced, Randomized, Two-treatment, Two-period, Two Sequence, Single Dose, Crossover, Oral Bioequivalence Study of Metoprolol Succinate Extended-Release Tablets 50 mg of Dr. Reddy's Laboratories Limited, India Comparing With That of TOPROL [NCT01694797]	Phase 1	48 participants (Actual)	Interventional	2011-01-31	Completed
A Double-blind, Randomized, Placebo-controlled, Multiple-dose, Multi-centre Safety and Efficacy Study of Co-administration of Tesofensine/Metoprolol in Subjects With Prader-Willi Syndrome (PWS) [NCT03149445]	Phase 2	18 participants (Actual)	Interventional	2017-03-30	Completed
Renin System Responses to Combined Renin Inhibition and Beta Adrenergic Blockade [NCT00627861]		1 participants (Actual)	Interventional	2008-11-30	Terminated(stopped due to The renin laboratory used in the study is no longer available.)
Comparison of Efficacy and Safety of Ivabradine Versus Metoprolol for Controlling Heart Rate Prior to 640-Slice Computed Tomographic Angiography in Elective Patients [NCT01755663]	Phase 4	60 participants (Anticipated)	Interventional	2014-12-31	Not yet recruiting
Economic Impact of Switching From Metoprolol to Nebivolol for Hypertension Treatment: A Retrospective Database Analysis [NCT01758263]		3,000 participants (Anticipated)	Observational	2012-10-31	Active, not recruiting
A Phase 2b, Double-blind, Randomized, Placebo-controlled, Multi-center, 16-week Dose Finding, Safety and Efficacy Study With Open-label Extension (OLE) Period of Tesomet in Subjects With Prader-Willi Syndrome [NCT05198362]	Phase 2	0 participants (Actual)	Interventional	2021-12-28	Withdrawn(stopped due to Due to financial considerations Sponsor is unable to complete the trial and assess the planned objectives/endpoints. No subjects have been randomized to treatment in the clinical trial and the decision therefore has no safety concern for patients)
Pharmacogenetic Prediction of Metoprolol Effectiveness [NCT02293096]		462 participants (Actual)	Interventional	2014-09-30	Terminated(stopped due to Study was terminated due to the change in funding.)
Nebivolol and Endothelial Regulation of Fibrinolysis [NCT01595516]	Phase 4	44 participants (Actual)	Interventional	2012-02-29	Completed
Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: A Randomized, Placebo-controlled, 2x2 Factorial, Double Blind Trial of Candesartan and Metoprolol [NCT01434134]	Phase 2	130 participants (Actual)	Interventional	2011-09-30	Completed
A Prospective Controlled Study for the Treatment Effect of Different Intervention Strategies for Pediatric Mitral Regurgitation--A Multicenter Prospective Cohort Study of Innovative Drug Therapy in Improving Left Ventricular Function After Mitral Repair [NCT06039592]		164 participants (Anticipated)	Observational [Patient Registry]	2022-04-01	Recruiting
A Comprehensive Research of Pediatric Heart Failure--A Prospective Cohort Study of Drug Therapy for Pediatric Heart Failure [NCT06039540]		200 participants (Anticipated)	Observational [Patient Registry]	2022-01-01	Recruiting
A Prospective Controlled Study for the Treatment Effect of Different Intervention Strategies for Pediatric Mitral Regurgitation--A Multicenter Prospective Cohort Study of Innovative Drug Therapy for Pediatric Mitral Regurgitation [NCT06037434]		122 participants (Anticipated)	Observational [Patient Registry]	2022-04-01	Recruiting
Carvedilol for Prevention of Paroxysmal Atrial Fibrillation [NCT01608893]		300 participants (Anticipated)	Interventional	2012-05-31	Active, not recruiting
Premedication With Atenolol Versus Metoprolol for Controlled Hypotensive Anesthesia During Nasal Surgeries. A Randomized Clinical Trial [NCT04914234]	Phase 4	60 participants (Anticipated)	Interventional	2022-12-15	Recruiting
Randomized Evaluation of Decreased Usage of betablocCkErs After Myocardial Infarction in the SWEDEHEART Registry - A Registry-based, Randomized, Parallel, Open-label, Multicenter Trial (REDUCE-SWEDEHEART) [NCT03278509]	Phase 4	5,000 participants (Anticipated)	Interventional	2017-09-11	Active, not recruiting
The Study Was Approved by the Ethics Committee of Our Institution, Which is Accredited by the Office of Human Research Protection as an Institutional Review Board [NCT02408172]	Phase 2/Phase 3	20 participants (Anticipated)	Interventional	2013-10-31	Recruiting
A Single Site, Interventional, Comparative Study to Evaluate the Safety and Efficacy of Ranolazine Plus Metoprolol Combination vs. FlecainidE pluS Metoprolol Combination in ATrial Fibrillation Recurrences [NCT03162120]	Phase 2/Phase 3	0 participants (Actual)	Interventional	2018-09-01	Withdrawn(stopped due to new study type, it will be re-organiZed as an Investigator Initiated Study (IIS))
Effect of Nebivolol on Oxidative Stress and Endothelial Progenitor Cells in Subjects With Hypertension [NCT01041287]	Phase 4	96 participants (Actual)	Interventional	2009-12-31	Completed
Nebivolol and the Endothelin (ET)-1 System [NCT01395329]	Phase 4	42 participants (Actual)	Interventional	2011-05-31	Completed
The Effects of Nifedipine and Metoprolol on Blood Pressure Variability in Northern Chinese: a Randomized Crossover Study [NCT02513927]	Phase 2/Phase 3	40 participants (Anticipated)	Interventional	2015-08-31	Recruiting
Adjuvant Treatment of Graves´ Ophthalmopathy With NSAID (aGO Study) [NCT01458600]	Phase 4	65 participants (Actual)	Interventional	2006-09-30	Completed
The Effect of Nebivolol on Endothelial Dysfunction in African Americans With Hypertension [NCT01049009]	Phase 4	91 participants (Actual)	Interventional	2009-12-31	Completed
The Impact of Nebivolol Versus Metoprolol on Quality of Life Measures and Cost-effectiveness in Stable Renal Transplant Recipients [NCT01441570]		11 participants (Actual)	Interventional	2012-02-29	Terminated(stopped due to due to slow enrollment)
The CAMERA Study: CArvedilol MEtoprolol Respiratory Assessment Investigator Trial [NCT00384566]	Phase 4	0 participants (Actual)	Interventional	2005-06-30	Withdrawn(stopped due to In order to join forces with another study already running which aims to answer the same question.)
Safety and Efficacy of Drug-Coated Balloon Angioplasty for the Treatment of Chronic Total Occlusions [NCT04744571]		200 participants (Anticipated)	Interventional	2021-02-28	Enrolling by invitation
A Randomized, Open-label, Single-dose, Parallel-arm, Phase 1 Study to Investigate the Pharmacokinetic Profile of a Fixed-Dose Combination Tablet of Tesofensine and Metoprolol (Tesomet) and Co-Administration of Tesofensine Plus Commercial Metoprolol in Adu [NCT03286829]	Phase 1	60 participants (Actual)	Interventional	2017-12-18	Completed
Radiofrequency Ablation for Atrial Fibrillation in Advanced Chronic Heart Failure [NCT00292162]		41 participants (Actual)	Interventional	2007-01-31	Completed
Beta-Blockers for the Prevention of Acute Exacerbations of COPD [NCT02587351]	Phase 3	532 participants (Actual)	Interventional	2016-05-01	Terminated(stopped due to Futility)
A Double-blind, Randomized, Placebo-controlled, Multiple-dose, Two-center, Safety and Efficacy Study of Co-administration of Tesofensine/Metoprolol Treatment in Subjects With Type 2 Diabetes Mellitus (T2DM) [NCT02737891]	Phase 2	60 participants (Actual)	Interventional	2016-04-30	Completed
Improving Right Ventricular Function in Young Adults Born Preterm: A Pilot Study [NCT03696758]	Phase 2	10 participants (Actual)	Interventional	2018-10-30	Completed
Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) [NCT00246519]	Phase 4	1,701 participants (Actual)	Interventional	2005-10-31	Completed
Mechanisms of Fenofibrate and Propranolol Alone or Combined in Burn Patients [NCT02452255]	Phase 2/Phase 3	18 participants (Actual)	Interventional	2015-11-30	Terminated(stopped due to Shriner's Burn Hospital closed the study and access to study-related data is unavailable. We are unable to submit the additional information or results-data)
An Open-label Crossover Trial Assessing the Value of Dabigatran in a Drug Interaction Cocktail in Healthy Young Volunteers [NCT02361619]	Phase 1	16 participants (Actual)	Interventional	2015-02-28	Completed
An International Randomised Controlled Trial to Establish the Effects of Early Intensive Blood Pressure Lowering in Patients With Intracerebral Haemorrhage. [NCT00716079]		2,839 participants (Actual)	Interventional	2008-09-30	Completed
Reducing Total Cardiovascular Risk in an Urban Community [NCT00241904]	Phase 4	525 participants (Actual)	Interventional	2006-05-31	Completed
Influence of CPB and Mini CPB to the Absorption of the Metoprolol After CABG [NCT01728272]		45 participants (Anticipated)	Interventional	2012-11-30	Recruiting
A Pilot Study of Plasma Renin Activity Guided vs Generic Combination Therapy for Hypertension [NCT01658657]		17 participants (Actual)	Interventional	2012-10-31	Completed
Comparative Effects of Nebivolol and Metoprolol on Female Sexual Function [NCT00995072]		29 participants (Actual)	Interventional	2009-10-31	Completed
Comparison of Bisoprolol With Metoprolol Succinate Sustained-release on Heart Rate and Blood Pressure in Hypertensive Patients (CREATIVE Study) [NCT01508325]	Phase 4	186 participants (Actual)	Interventional	2011-12-31	Completed
Is Labetalol More Effective Than Metoprolol for Controlled Hypotensive Anesthesia During Endoscopic Nasal Surgeries? A Randomized Clinical Trial. [NCT05368376]	Phase 4	60 participants (Actual)	Interventional	2021-04-01	Completed
GENETIC-AF - A Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Toprol-XL for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients With Heart Failure [NCT01970501]	Phase 2	267 participants (Actual)	Interventional	2014-04-30	Completed
An Open Label, Balanced, Randomized, Two-treatment, Two-period, Two Sequence, Single Dose, Crossover, Oral Bioequivalence Study of Metoprolol Succinate Extended-Release Tablets 200mg of Dr. Reddy's Laboratories Limited, India Comparing With That of TOPROL [NCT01673997]	Phase 1	48 participants (Actual)	Interventional	2010-12-31	Completed
A Randomized Controlled Trial to Compare Prophylaxis With Oral Ascorbic Acid, Oral Amiodarone or Both in Combination With Beta Blockers to Reduce Postoperative Atrial Fibrillation After Cardiac Surgery [NCT00953212]	Phase 3	304 participants (Actual)	Interventional	2009-08-31	Completed
Racial Differences in the Natriuretic Peptide Response to Exercise and Beta-blockers [NCT03070184]	Phase 2	80 participants (Actual)	Interventional	2017-04-30	Active, not recruiting
Study of Curative Effect Evaluation of Shexiang Baoxin Pill on Coronary Artery Disease Not Amenable to Revascularization on the Basis of Western Medicine Therapy [NCT03072121]	Phase 4	440 participants (Anticipated)	Interventional	2017-06-30	Not yet recruiting
Treatment of Ventricular Tachyarrhythmias Refractory To Shock With Beta Blockers: The SHOCK and BLOCK Trial [NCT00401882]	Phase 2	7 participants (Actual)	Interventional	2007-01-31	Terminated(stopped due to Difficult accrual)
The Antihypertensives and Vascular, Endothelial and Cognitive Function Trial (AVEC Trial) [NCT00605072]	Phase 2	53 participants (Actual)	Interventional	2008-01-31	Completed
Acute Cardioversion Versus Wait And See-approach for Symptomatic Atrial Fibrillation in the Emergency Department (RACE 7 ACWAS-trial) [NCT02248753]		437 participants (Actual)	Interventional	2014-10-31	Completed
DiME Study: Comparison of Diltiazem and Metoprolol in the Management of Acute Atrial Fibrillation or Atrial Flutter With Rapid Ventricular Response: A Prospective Randomized and Double-Blinded Non-Inferiority Trial of Safety and Efficacy [NCT01914926]	Phase 4	54 participants (Actual)	Interventional	2009-06-30	Completed
Flucloxacillin as an Inducer of CYP-enzymes [NCT04840641]	Phase 1	14 participants (Actual)	Interventional	2021-03-25	Completed
A Phase 1 Study to Examine Pharmacodynamic Interaction Between Tesofensine and Metoprolol on 24-hours Mean Heart Rate [NCT03488719]	Phase 1	37 participants (Actual)	Interventional	2018-07-10	Completed
Comparison of Efficacy and Safety of S-Metoprolol XR 25-50 mg Tablets and Metoprolol Zok 50-100 mg Tablets in Hypertensive Patients. [NCT04457323]	Phase 4	126 participants (Anticipated)	Interventional	2022-01-15	Not yet recruiting
Assessment of Intravenous Rate Control Response in Atrial Fibrillation Trial Pilot Study (AIRCRAFT) [NCT04234477]	Phase 4	0 participants (Actual)	Interventional	2021-12-31	Withdrawn(stopped due to The study was not IRB approved and there were anticipated challenges in recruiting participants.)
Effect of Nebivolol Compared With Metoprolol in Hypertensive Patients With Peripheral Arterial Disease [NCT01499134]	Phase 3	17 participants (Actual)	Interventional	2011-08-31	Completed
A Phase 2b, Double-blind, Randomized, Placebo-controlled, Dose-finding, Multi-center, 36-week Safety and Efficacy Study With Open-label Extension (OLE) Period of Tesomet in Subjects With Hypothalamic Obesity [NCT05147415]	Phase 2	0 participants (Actual)	Interventional	2021-11-11	Withdrawn(stopped due to Due to financial considerations Sponsor is unable to complete the trial and assess the planned objectives/endpoints. No subjects have been randomized to treatment in the clinical trial and the decision therefore has no safety concern for patients)
The Success of Opening Concurrent Chronic Total Occlusion leSion to Improve Cardiac Function Trial in Patients With Multi-vessel Disease (SOS-moral): Study Protocol of a Prospective Multicenter Study [NCT03372785]		240 participants (Anticipated)	Observational [Patient Registry]	2018-04-10	Enrolling by invitation
Randomized Open-Label Crossover Trial Comparing Tolerability of a Cardioselective Beta-Blocker (Metoprolol-Succinate-ER) and a Non-Cardioselective Beta-Blocker (Carvedilol) in Patients With Chronic Obstructive Pulmonary Disease [NCT03370835]	Phase 4	21 participants (Actual)	Interventional	2004-06-30	Completed
Can Nebivolol Reverse Inappropriate Left Ventricular Mass in Hypertensive Patients? [NCT01605370]	Phase 4	1 participants (Actual)	Interventional	2012-06-30	Terminated(stopped due to Difficulty in identifying subjects satisfying the inclusion criteria.)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Trial	Outcome
NCT00000620 (6) [back to overview]	Stroke in the Blood Pressure Trial.
NCT00000620 (6) [back to overview]	First Occurrence of MCE or Revascularization or Hospitalization for Congestive Heart Failure (CHF) in Lipid Trial.
NCT00000620 (6) [back to overview]	First Occurrence of Major Cardiovascular Event (MCE) in the Blood Pressure Trial.
NCT00000620 (6) [back to overview]	First Occurrence of a Major Cardiovascular Event (MCE); Specifically Nonfatal Heart Attack, Nonfatal Stroke, or Cardiovascular Death (Measured Throughout the Study) in the Glycemia Trial.
NCT00000620 (6) [back to overview]	Death From Any Cause in the Glycemia Trial.
NCT00000620 (6) [back to overview]	First Occurrence of Major Cardiovascular Event (MCE) in the Lipid Trial.
NCT00123604 (1) [back to overview]	Flow Mediated Dilation
NCT00142584 (3) [back to overview]	Change in Average Sitting Diastolic Blood Pressure (DBP) Taken at Trough at the End of Treatment Compared to Baseline
NCT00142584 (3) [back to overview]	Number of Participants With Treatment Emergent Adverse Events (TEAEs)
NCT00142584 (3) [back to overview]	Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline
NCT00241904 (4) [back to overview]	Patients' Satisfaction With Care and Health Care Utilization
NCT00241904 (4) [back to overview]	Systolic Blood Pressure
NCT00241904 (4) [back to overview]	HbA1c
NCT00241904 (4) [back to overview]	Low-density Lipoprotein Cholesterol
NCT00246519 (1) [back to overview]	Blood Pressure Response (Delta BP (After 18 Weeks of Medication - Baseline)).
NCT00273052 (14) [back to overview]	Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) Levels by Treatment Group at Maintenance Month 6
NCT00273052 (14) [back to overview]	Change From Baseline in Hemoglobin A1c (HbA1c) (Glycemic Parameter) by Treatment Group at Maintenance Month 6
NCT00273052 (14) [back to overview]	Change From Baseline in c-Peptide (Glycemic Parameter) by Treatment Group at Maintenance Month 6
NCT00273052 (14) [back to overview]	Change From Baseline in Fasting Insulin (Glycemic Parameter) by Treatment Group at Maintenance Month 6
NCT00273052 (14) [back to overview]	Change From Baseline in Log Transformed Lipoprotein-associated Phospholipase A2 (LpPLA2) by Treatment Group at Maintenance Month 6
NCT00273052 (14) [back to overview]	Change From Baseline in Blood Pressure by Treatment Group at Maintenance Month 6
NCT00273052 (14) [back to overview]	Change From Baseline in Fasting Plasma Glucose (FPG) (Glycemic Parameter) by Treatment Group at Maintenance Month 6
NCT00273052 (14) [back to overview]	Change From Baseline in Additional Lipid Parameters by Treatment Group With Unit of Measures of mg/dL at Maintenance Month 6
NCT00273052 (14) [back to overview]	Change From Baseline in Additional Lipid Parameters by Treatment Group With Unit of Measures of g/L at Maintenance Month 6
NCT00273052 (14) [back to overview]	Change From Baseline in Weight by Treatment Group at Maintenance Month
NCT00273052 (14) [back to overview]	Change From Baseline in Triglycerides Levels by Treatment Group at Maintenance Month 6
NCT00273052 (14) [back to overview]	Change From Baseline in Heart Rate by Treatment Group at Maintenance Month 6
NCT00273052 (14) [back to overview]	Change From Baseline in Log Transformed High Sensitivity C-reactive Protein (Hs-CRP) by Treatment Group at Maintenance Month 6
NCT00273052 (14) [back to overview]	Change From Baseline in Homeostasis Model Assessment (Glycemic Parameter) by Treatment Group at Maintenance Month 6
NCT00292162 (6) [back to overview]	Plasma B-type Natriuretic Peptide (BNP) at Baseline
NCT00292162 (6) [back to overview]	Plasma B-type Natriuretic Peptide (BNP) at 6 Months
NCT00292162 (6) [back to overview]	Plasma B-type Natriuretic Peptide (BNP)
NCT00292162 (6) [back to overview]	Baseline Left Ventricular Ejection Fraction by Magnetic Resonance Imaging (MRI)
NCT00292162 (6) [back to overview]	Change in Left Ventricular Ejection Fraction by Magnetic Resonance Imaging (MRI)%
NCT00292162 (6) [back to overview]	Left Ventricular Ejection Fraction by Magnetic Resonance Imaging (MRI)at 6 Months
NCT00391846 (8) [back to overview]	Composite Value of 3 Variables After 9 Months: Cardiovascular Death (Days Alive), Cardiovascular Hospitalization (Days Out of Hospital), Heart Failure Symptoms (Symptom Score Subset of the Kansas City Cardiomyopathy Questionnaire - Questions 3,5,7,9)
NCT00391846 (8) [back to overview]	Discontinuations
NCT00391846 (8) [back to overview]	Number of CV Deaths
NCT00391846 (8) [back to overview]	Number of Days in Hospital for CV Reason
NCT00391846 (8) [back to overview]	Total Number of Titration Steps in Prescribed Heart Failure Treatment
NCT00391846 (8) [back to overview]	Changes in Health-related Quality of Life
NCT00391846 (8) [back to overview]	Changes in Heart Failure Symptoms
NCT00391846 (8) [back to overview]	Changes in NT-proBNP Values Over Time in All Patients
NCT00401882 (3) [back to overview]	Survival to Hospital Discharge
NCT00401882 (3) [back to overview]	Adverse Effects
NCT00401882 (3) [back to overview]	Return of Spontaneous Circulation
NCT00589303 (1) [back to overview]	Cardiac Hospitalization Within Six Months of Enrollment
NCT00605072 (5) [back to overview]	Cognitive Assessment: Trail Making Test Part B
NCT00605072 (5) [back to overview]	Cognitive Assessment: Hopkins Verbal Learning- Immediate Recall
NCT00605072 (5) [back to overview]	Cognitive Assessment: Forward Digit Span Test
NCT00605072 (5) [back to overview]	Blood Pressure Outcome: Systolic BP
NCT00605072 (5) [back to overview]	Blood Flow Velocity, Sitting
NCT00627861 (3) [back to overview]	Plasma Renin Activity
NCT00627861 (3) [back to overview]	Blood Pressure
NCT00627861 (3) [back to overview]	Plasma Renin Concentration
NCT00642434 (1) [back to overview]	Number of Participants Assessed for Change in Markers of Inflammation (PAI-1) Following Treatment Compared to Baseline
NCT00661895 (1) [back to overview]	Percentage of Subjects Achieving Blood Pressure Goals
NCT00716079 (2) [back to overview]	A Composite of Death or Dependency, With Dependency Being Defined by a Score of 3 to 5 on the Modified Rankin Scale (mRS)
NCT00716079 (2) [back to overview]	Death at 90 Days
NCT00744237 (2) [back to overview]	Change From Baseline in Insulin Resistance Based on Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
NCT00744237 (2) [back to overview]	Change From Baseline in Mean Glycosylated Hemoglobin (HbA1c) at Week 26
NCT00756236 (1) [back to overview]	Area Under the Curve of etSEV Over the First Hour
NCT00775671 (2) [back to overview]	Measurement of Insulin Sensitivity
NCT00775671 (2) [back to overview]	Marker of Fibrinolysis
NCT00829296 (4) [back to overview]	Change in Augmentation Index
NCT00829296 (4) [back to overview]	Change in Central Systolic Blood Pressure (SBP)
NCT00829296 (4) [back to overview]	Change in Pulse Pressure Amplification
NCT00829296 (4) [back to overview]	Change in Pulse Wave Velocity (PWV)
NCT00849810 (1) [back to overview]	Primary Outcome is Pre- and Post-treatment Ambulatory Blood Pressure.
NCT00953212 (12) [back to overview]	Occurrence of Post-operative Atrial Fibrillation Requiring Treatment After Open Heart Surgery
NCT00953212 (12) [back to overview]	Number of Participants With Stroke
NCT00953212 (12) [back to overview]	Number of Participants With Respiratory Failure Requiring Reintubation
NCT00953212 (12) [back to overview]	Number of Participants With Readmission to ICU for Treatment of Atrial Fibrillation
NCT00953212 (12) [back to overview]	Number of Participants With Readmission to Hospital for Treatment of Atrial Fibrillation
NCT00953212 (12) [back to overview]	Number of Participants With Postoperative Vasoplegia
NCT00953212 (12) [back to overview]	Number of Participants With Mortality
NCT00953212 (12) [back to overview]	Number of Participants With Low Output Heart Failure
NCT00953212 (12) [back to overview]	Number of Participants With Bradycardia Necessitating Permanent Pacemaker Placement
NCT00953212 (12) [back to overview]	Number of Participants With Acute Kidney Injury
NCT00953212 (12) [back to overview]	ICU Length of Stay
NCT00953212 (12) [back to overview]	Hospital Length of Stay
NCT00992056 (1) [back to overview]	Change in 24-hour Mean Systolic Blood Pressure by ABPM From Day 5 of Low Sodium to Day 10 of High Sodium
NCT00993421 (14) [back to overview]	Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to 24 Weeks Endpoint
NCT00993421 (14) [back to overview]	Change in Body Composition Using Dual Energy X-ray Absorptiometry (DXA) From Baseline to 24 Week Endpoint
NCT00993421 (14) [back to overview]	The Mean Change in Body Weight From Baseline to 24 Week Endpoint
NCT00993421 (14) [back to overview]	Percentage of Participants Who Achieve a Minimum of 10% Weight Loss From Baseline at 24 Weeks
NCT00993421 (14) [back to overview]	Percentage Change in Waist Circumference From Baseline to 24 Week Endpoint
NCT00993421 (14) [back to overview]	Percent Change in Body Weight From Baseline to 24 Week Endpoint
NCT00993421 (14) [back to overview]	Change in Waist Circumference From Baseline to 24 Week Endpoint
NCT00993421 (14) [back to overview]	Change in Blood Pressure From Baseline to 24 Week Endpoint
NCT00993421 (14) [back to overview]	Change in Triglycerides From Baseline to 24 Weeks Endpoint
NCT00993421 (14) [back to overview]	Change in Total Cholesterol From Baseline to 24 Weeks Endpoint
NCT00993421 (14) [back to overview]	Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to 24 Weeks Endpoint
NCT00993421 (14) [back to overview]	Change in Heart Rate From Baseline to 24 Week Endpoint
NCT00993421 (14) [back to overview]	Change From Baseline in Vitality Scale of Medical Outcomes Short Form - 36 (SF-36) Scale
NCT00993421 (14) [back to overview]	Change From Baseline for Obesity Weight Loss Quality of Life Instrument (OWL-QoL)
NCT00995072 (2) [back to overview]	Change in Sexual Functioning Questionnaire Score
NCT00995072 (2) [back to overview]	Change in Female Sexual Function Index
NCT00999102 (2) [back to overview]	Treadmill Exercise Time After 4 Weeks of Treatment on Each Drug/Dose Combination.
NCT00999102 (2) [back to overview]	Multidimensional Assessment of Fatigue (MAF) Questionnaire: Global Fatigue Score After 4 Weeks of Treatment on Each Drug/Dose Combination.
NCT01041287 (3) [back to overview]	Pulse Wave Velocity (Measure of Arterial Stiffness)
NCT01041287 (3) [back to overview]	Pulse Wave Velocity (Measure of Arterial Stiffness)
NCT01041287 (3) [back to overview]	Pulse Wave Velocity (Measure of Arterial Stiffness)
NCT01044693 (4) [back to overview]	Change in Heart Rate During the Night
NCT01044693 (4) [back to overview]	Nocturnal Urinary Sodium Excretion
NCT01044693 (4) [back to overview]	Change in Systolic Blood Pressure During the Night
NCT01044693 (4) [back to overview]	Orthostatic Tolerance the Following Morning
NCT01049009 (2) [back to overview]	Endothelial Function Measured by Forearm Blood Flow (FBF) at 24 Weeks
NCT01049009 (2) [back to overview]	Endothelial Function Measured by Forearm Blood Flow (FBF) at 12 Weeks
NCT01052428 (7) [back to overview]	Left Ventricular Ejection Fraction
NCT01052428 (7) [back to overview]	Peak Early Filling Rate: Rate of Change Over Time
NCT01052428 (7) [back to overview]	Left Ventricular End-diastolic Mass Indexed to Left Ventricular End-diastolic Volume
NCT01052428 (7) [back to overview]	Left Ventricular End-Diastolic Radius to Wall Thickness
NCT01052428 (7) [back to overview]	Left Ventricular End Systolic Volume Indexed to Body Surface Area
NCT01052428 (7) [back to overview]	Left Ventricular End Diastolic Volume Indexed to Body Surface Area
NCT01052428 (7) [back to overview]	Systolic Longitudinal Strain
NCT01157234 (11) [back to overview]	Percent Change in Plasma Nitric Oxide Level From Baseline to Month-twelve of Treatment With Nebivolol in Transplant Recipients >/= 50 Years Old Compared With Nebivolol in Transplant Recipients < 50 Years Old.
NCT01157234 (11) [back to overview]	Plasma Nitric Oxide Level Change From Baseline to Month 12 Between the Groups.
NCT01157234 (11) [back to overview]	Systolic Blood Pressure (Millimeter, Mercury) Change From Baseline to Month-12 of Treatment Between the Groups
NCT01157234 (11) [back to overview]	Number of Antihypertensive Drug Classes Change From Baseline to Month-12 Between the Groups.
NCT01157234 (11) [back to overview]	Percent Change in Plasma Nitric Oxide Level From Baseline to Month-12 of Treatment With Nebivolol in Transplant Recipients >/= 50 Years Old Compared With Metoprolol in Transplant Recipients Age >/= 50 Years Old.
NCT01157234 (11) [back to overview]	Diastolic Blood Pressure (Millimeter, Mercury) Change From Baseline to Month-12 Between the Groups
NCT01157234 (11) [back to overview]	Estimated Glomerular Filtration Rate (ml/Minute) Change From Baseline to Month-12 Between the Groups
NCT01157234 (11) [back to overview]	Percent Change in Plasma Nitric Oxide Level From Baseline to Month-12 of Treatment With Nebivolol in Transplant Recipients <50 Years Old Compared With Metoprolol in Transplant Recipients >/= 50 Years Old.
NCT01157234 (11) [back to overview]	Percent Change in Plasma Nitric Oxide Level From Baseline to Month-12 of Treatment With Nebivolol in Transplant Recipients < 50 Years Old Compared With Metoprolol in Transplant Recipients < 50 Years Old
NCT01157234 (11) [back to overview]	Plasma Nitric Oxide Level (Nmol/L) at Month-12 Between the Groups.
NCT01157234 (11) [back to overview]	Mean Arterial Blood Pressure (Millimeter, Mercury) Change From Baseline to Month-12 Between the Groups
NCT01203852 (2) [back to overview]	Adverse Metabolic Effects
NCT01203852 (2) [back to overview]	Change in Blood Pressure From Baseline to Treatment
NCT01213173 (13) [back to overview]	The Change From Baseline in Total Cholesterol
NCT01213173 (13) [back to overview]	The Impact on 24-hr Average Heart Rate Between Two Groups (Betaloc ZOK® 95mg vs. 190mg)
NCT01213173 (13) [back to overview]	The Difference of Change From Baseline in Total Ischemic Burden Between Groups
NCT01213173 (13) [back to overview]	The Difference of Change From Baseline in Angina Frequency Between Groups
NCT01213173 (13) [back to overview]	The Proportion of Patients With Resting Heart Rate Controlled to ≤60bpm Between Groups
NCT01213173 (13) [back to overview]	The Proportion of Patients With Resting Heart Rate Controlled to ≤60bpm Between Groups
NCT01213173 (13) [back to overview]	The Different Impact on 24-hr Average Heart Rate Between Two Groups
NCT01213173 (13) [back to overview]	The Change From Baseline in Fasting Plasma Glucose
NCT01213173 (13) [back to overview]	The Impact on 24-hr Average Heart Rate From Baseline Within Groups
NCT01213173 (13) [back to overview]	The Change From Baseline in Triglycerides
NCT01213173 (13) [back to overview]	The Different Impact on 24-hr Average Heart Rate From Baseline Within Groups
NCT01213173 (13) [back to overview]	The Difference of Change From Baseline in Total Ischemic Burden Between Groups
NCT01213173 (13) [back to overview]	The Difference of Change From Baseline in Angina Frequency Between Groups
NCT01324388 (8) [back to overview]	Pharmacokinetics, Area Under the Concentration Curve (AUC) of Metoprolol When Administered With LY2189265
NCT01324388 (8) [back to overview]	Pharmacokinetics, Maximum Concentration (Cmax) of Lisinopril
NCT01324388 (8) [back to overview]	Pharmacokinetics, Maximum Concentration (Cmax) of Metoprolol When Administered With LY2189265
NCT01324388 (8) [back to overview]	Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol
NCT01324388 (8) [back to overview]	Mean, 24-hour Blood Pressure (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril
NCT01324388 (8) [back to overview]	Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Lisinopril
NCT01324388 (8) [back to overview]	Mean, 24-hour Heart Rate (Collected by Ambulatory Blood Pressure Monitoring [ABPM]) in Response to Co-administration of LY2189265 and Metoprolol
NCT01324388 (8) [back to overview]	Pharmacokinetics, Area Under the Concentration Curve (AUC) of Lisinopril
NCT01337674 (4) [back to overview]	Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel A
NCT01337674 (4) [back to overview]	Percentage of Participants With a Clinical or Laboratory Adverse Experience
NCT01337674 (4) [back to overview]	Steady-state Area Under the Plasma Concentration Versus Time Curve (AUC0-24hr) for MK-4618
NCT01337674 (4) [back to overview]	Maximum Change From Baseline in Semi-recumbent and Standing Systolic Blood Pressure: Panel B
NCT01395329 (7) [back to overview]	Systolic Blood Pressure
NCT01395329 (7) [back to overview]	Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min)
NCT01395329 (7) [back to overview]	Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min)
NCT01395329 (7) [back to overview]	FBF Response to Sodium Nitroprusside
NCT01395329 (7) [back to overview]	FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788)
NCT01395329 (7) [back to overview]	Diastolic Blood Pressure
NCT01395329 (7) [back to overview]	FBF Response to Acetylcholine (ACh)
NCT01441570 (2) [back to overview]	Quality of Life
NCT01441570 (2) [back to overview]	Blood Pressure
NCT01499134 (8) [back to overview]	Ankle-brachial Index (ABI)
NCT01499134 (8) [back to overview]	Claudication Onset Time (COT)
NCT01499134 (8) [back to overview]	Peak Walking Time (PWT)
NCT01499134 (8) [back to overview]	Walking Impairment Questionnaire (WIQ) - Change Calf Pain
NCT01499134 (8) [back to overview]	Walking Impairment Questionnaire (WIQ) - Change in Buttock Pain
NCT01499134 (8) [back to overview]	Walking Impairment Questionnaire (WIQ) - Change in WIQ Distance Score
NCT01499134 (8) [back to overview]	Walking Impairment Questionnaire (WIQ) - Change in WIQ Speed Score
NCT01499134 (8) [back to overview]	Walking Impairment Questionnaire (WIQ) - Change in WIQ Stairs Score
NCT01501929 (2) [back to overview]	Microvascular Blood Flow
NCT01501929 (2) [back to overview]	Endothelial Cell Protein Expression p47phox From Endothelial Cell Collection
NCT01502787 (3) [back to overview]	Blood Pressure During Exercise
NCT01502787 (3) [back to overview]	Blood Pressure During Angiotensin II Infusion
NCT01502787 (3) [back to overview]	Forearm Blood Flow
NCT01508325 (12) [back to overview]	Change From Baseline in Mean Heart Rate in the Last 4 Hours After 12-week Treatment
NCT01508325 (12) [back to overview]	Change From Baseline in Mean Ambulatory Systolic Blood Pressure (SBP) in the Last 4 Hours After 12-week Treatment
NCT01508325 (12) [back to overview]	Change From Baseline in Mean Ambulatory Night-time Heart Rate at Week 12
NCT01508325 (12) [back to overview]	Change From Baseline in Mean Ambulatory Daytime Heart Rate at Week 12
NCT01508325 (12) [back to overview]	Change From Baseline in Mean Ambulatory Daytime Blood Pressure at Week 12
NCT01508325 (12) [back to overview]	Change From Baseline in Mean Ambulatory 24-hour Heart Rate at Week 12
NCT01508325 (12) [back to overview]	Change From Baseline in Mean Ambulatory 24-hour Blood Pressure at Week 12
NCT01508325 (12) [back to overview]	Heart Rate Response Rate
NCT01508325 (12) [back to overview]	Change From Baseline in Mean Ambulatory Diastolic Blood Pressure (DBP) in the Last 4 Hours After 12-week Treatment
NCT01508325 (12) [back to overview]	Change From Baseline in 24-hour Blood Pressure Variability at Week 12
NCT01508325 (12) [back to overview]	Change From Baseline in Mean Ambulatory Night-time Blood Pressure at Week 12
NCT01508325 (12) [back to overview]	Blood Pressure Response Rate
NCT01523002 (6) [back to overview]	World Health Organization (WHO) Treatment Emergent Adverse Events
NCT01523002 (6) [back to overview]	Arm A Pharmacokinetic Parameters of Metoprolol & α-hydroxymetoprolol: Area Under Curve (AUC)0-t, AUC0-∞
NCT01523002 (6) [back to overview]	Arm A Pharmacokinetics Parameters of Metoprolol & α-hydroxymetoprolol: Cmax
NCT01523002 (6) [back to overview]	Arm A Pharmacokinetics Parameters of Metoprolol & α-hydroxymetoprolol: t1/2
NCT01523002 (6) [back to overview]	Arm A Pharmacokinetics Parameters of Metoprolol & α-hydroxymetoprolol: Tmax
NCT01523002 (6) [back to overview]	Non-WHO Listed Treatment Emergent Adverse Events
NCT01595516 (6) [back to overview]	Systolic Blood Pressure
NCT01595516 (6) [back to overview]	Heart Rate
NCT01595516 (6) [back to overview]	Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention
NCT01595516 (6) [back to overview]	Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy.
NCT01595516 (6) [back to overview]	Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy.
NCT01595516 (6) [back to overview]	Diastolic Blood Pressure
NCT01658657 (1) [back to overview]	Blood Pressure Control, as Defined as Office BP Measurement of <140 mmHg Systolic and <90 mmHg Diastolic
NCT01798992 (3) [back to overview]	Composite of All-cause Mortality, Need for Heart Transplant or Need for Ventricular Assist Device.
NCT01798992 (3) [back to overview]	Improvement in Left Ventricular Ejection Fraction (LVEF) at 12 Months
NCT01798992 (3) [back to overview]	Improvement in LVEF at 3 Months
NCT01837069 (2) [back to overview]	Number of Partipants That Experienced Death, Myocardial Infarction, Stroke, Transient Ischemic Attack, Myocardial Necrosis, or Venous Thromboembolism
NCT01837069 (2) [back to overview]	Length of Stay
NCT01914926 (1) [back to overview]	Percent of Patients Reaching Target HR<100bpm Within 30 Minutes
NCT01970501 (4) [back to overview]	Number of Patients With Adequate Ventricular Rate Control During the 24-week Follow-up Period
NCT01970501 (4) [back to overview]	Total Number of Hospitalization Days Per Patient (All-cause) During the Total Study Period (24 Weeks)
NCT01970501 (4) [back to overview]	Time to First Event of Symptomatic or Asymptomatic AF/AFL or ACM During the 24-week Follow-up Period After Establishment of Stable SR on Study Drug [End of Treatment Week 24]
NCT01970501 (4) [back to overview]	Time to First Event of Symptomatic Atrial Fibrillation/Atrial Flutter (AF/AFL) or All Cause Mortality (ACM) During the 24-week Follow-up Period After Establishment of Stable Sinus Rhythm (SR) on Study Drug [End of Treatment Week 24].
NCT02293096 (4) [back to overview]	Adverse Drug Events: CYP2D6 Metabolizer Status
NCT02293096 (4) [back to overview]	Adverse Drug Events: ADRB1 Genotype
NCT02293096 (4) [back to overview]	Blood Pressure Decline
NCT02293096 (4) [back to overview]	Heart Rate Decline
NCT02336607 (12) [back to overview]	The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among the Subjects Who Reached Target at 4 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.
NCT02336607 (12) [back to overview]	The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among the Subjects Who Reached Target at 2 Weeks of Felodipine Sustained Release, Alone
NCT02336607 (12) [back to overview]	The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among the Subjects Who Reached Target at 12 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.
NCT02336607 (12) [back to overview]	The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among the Subjects Who Reached Target After 8 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.
NCT02336607 (12) [back to overview]	The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among All Randomized Subjects After 8 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.
NCT02336607 (12) [back to overview]	The Change of Pulse Wave Velocity at 12 Weeks Compare With Baseline Data of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.
NCT02336607 (12) [back to overview]	The Percentage of Subjects Reaching Blood Pressure Target (Defined as < 140 / 90 mmHg) After 14 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.
NCT02336607 (12) [back to overview]	The Percentage of Subjects Reaching Blood Pressure Target (Defined as < 140 / 90 mmHg) After 8 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.
NCT02336607 (12) [back to overview]	The Change of Pulse Wave Velocity From Baseline at 2, 14 Weeks of Felodipine Sustained Release Alone.
NCT02336607 (12) [back to overview]	The Magnitude of Systolic and Diastolic Blood Pressure Change From Baseline Among All Randomized Subjects After 4 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.
NCT02336607 (12) [back to overview]	The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among All Randomized Subjects After 12 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.
NCT02336607 (12) [back to overview]	The Percentage of Subjects Reaching Blood Pressure Target (Defined as < 140 / 90 mmHg) After 4 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.
NCT02417246 (5) [back to overview]	Area Under the Plasma Concentration Versus Time Curve (AUC)
NCT02417246 (5) [back to overview]	Heart Rate (HR) Response Compared Between Brand Name Metoprolol ER and Each Generic (Generic B, Generic A) Formulation of Metoprolol Succinate
NCT02417246 (5) [back to overview]	Peak Plasma Concentration (Cmax) of Metoprolol Succinate
NCT02417246 (5) [back to overview]	The Heart Rate Variability (HRV) Response to Brand Name Metoprolol ER Versus Each Generic Formulation of Metoprolol Succinate.
NCT02417246 (5) [back to overview]	Blood Pressure Values (Systolic and Diastolic) Compared Between Brand Name Metoprolol ER and Each Generic Metoprolol Formulation (Generic B, Generic A)
NCT02484859 (5) [back to overview]	Time to Achieve Intraoperative Bleeding Score < 3
NCT02484859 (5) [back to overview]	Postoperative Pain
NCT02484859 (5) [back to overview]	Intraoperative Bleeding Score
NCT02484859 (5) [back to overview]	Bleeding Rate
NCT02484859 (5) [back to overview]	Number of Participants With Postoperative Nausea and Vomiting
NCT02587351 (24) [back to overview]	Incidence of Presumed Metoprolol-related Side-effects
NCT02587351 (24) [back to overview]	Major Adverse Cardiovascular Events
NCT02587351 (24) [back to overview]	Markers of Systemic Inflammation
NCT02587351 (24) [back to overview]	Short Form Health Survey (SF-36) Bodily Pain Scale
NCT02587351 (24) [back to overview]	Short Form Health Survey (SF-36) Emotional Well-being Scale
NCT02587351 (24) [back to overview]	Short Form Health Survey (SF-36) Energy/Fatigue Scale
NCT02587351 (24) [back to overview]	Short Form Health Survey (SF-36) General Health Scale
NCT02587351 (24) [back to overview]	Short Form Health Survey (SF-36) Physical Function Scale
NCT02587351 (24) [back to overview]	Short Form Health Survey (SF-36) Role Functioning - Emotional Scale
NCT02587351 (24) [back to overview]	Short Form Health Survey (SF-36) Role Functioning - Physical Scale
NCT02587351 (24) [back to overview]	Short Form Health Survey (SF-36) Social Functioning Scale
NCT02587351 (24) [back to overview]	All-cause Mortality
NCT02587351 (24) [back to overview]	COPD Assessment Test (CAT)
NCT02587351 (24) [back to overview]	Exercise Capacity as Assessed by the 6 Minute Walk Distance (6MWD)
NCT02587351 (24) [back to overview]	Forced Expiratory Volume in 1 Second (FEV1)
NCT02587351 (24) [back to overview]	Hospital Days Resulting From Acute Exacerbations of COPD
NCT02587351 (24) [back to overview]	Modified Medical Research Council Dyspnea Scale (MMRC)
NCT02587351 (24) [back to overview]	Number of Acute Exacerbations of COPD
NCT02587351 (24) [back to overview]	Number of Emergency Department Visits Resulting From Acute Exacerbations of COPD
NCT02587351 (24) [back to overview]	Number of Hospital Admissions Resulting From Acute Exacerbations of COPD
NCT02587351 (24) [back to overview]	San Diego Shortness of Breath Questionnaire (SOBQ)
NCT02587351 (24) [back to overview]	St. George's Respiratory Questionnaire (SGRQ)
NCT02587351 (24) [back to overview]	Time to First Occurrence of an Acute COPS Exacerbation
NCT02587351 (24) [back to overview]	Acute Exacerbations of COPD and MACE
NCT02737891 (3) [back to overview]	Change From Baseline to End of Treatment in Body Weight
NCT02737891 (3) [back to overview]	Change From Baseline to End of Treatment in HbA1c
NCT02737891 (3) [back to overview]	Effects of Co-administration of Tesofensine/Metoprolol Treatment vs. Placebo on 24-hour Mean Heart Rate
NCT02746575 (1) [back to overview]	Difference in hscTnI Values
NCT03286829 (3) [back to overview]	AUC0-48
NCT03286829 (3) [back to overview]	Tmax
NCT03286829 (3) [back to overview]	Cmax
NCT03696758 (20) [back to overview]	Right Ventricular Diastolic Volume Pre and Post Metoprolol
NCT03696758 (20) [back to overview]	Right Ventricular Diastolic Volume Pre and Post Sildenafil
NCT03696758 (20) [back to overview]	Right Ventricular Ejection Fraction Pre and Post Metoprolol
NCT03696758 (20) [back to overview]	Right Ventricular Ejection Fraction Pre and Post Sildenafil
NCT03696758 (20) [back to overview]	Right Ventricular Energetic Efficiency Pre and Post Metoprolol
NCT03696758 (20) [back to overview]	Right Ventricular Energetic Efficiency Pre and Post Sildenafil
NCT03696758 (20) [back to overview]	Right Ventricular Stroke Volume Pre and Post Sildenafil
NCT03696758 (20) [back to overview]	Right Ventricular Systolic Volume Pre and Post Metoprolol
NCT03696758 (20) [back to overview]	Right Ventricular Systolic Volume Pre and Post Sildenafil
NCT03696758 (20) [back to overview]	Left Ventricular Diastolic Volume Pre and Post Metoprolol
NCT03696758 (20) [back to overview]	Left Ventricular Systolic Volume Pre and Post Metoprolol
NCT03696758 (20) [back to overview]	Left Ventricular Diastolic Volume Pre and Post Sildenafil
NCT03696758 (20) [back to overview]	Left Ventricular Ejection Fraction Pre and Post Metoprolol
NCT03696758 (20) [back to overview]	Left Ventricular Ejection Fraction Pre and Post Sildenafil
NCT03696758 (20) [back to overview]	Left Ventricular Energetic Efficiency Pre and Post Metoprolol
NCT03696758 (20) [back to overview]	Left Ventricular Energetic Efficiency Pre and Post Sildenafil
NCT03696758 (20) [back to overview]	Left Ventricular Stroke Volume Pre and Post Metoprolol
NCT03696758 (20) [back to overview]	Left Ventricular Stroke Volume Pre and Post Sildenafil
NCT03696758 (20) [back to overview]	Left Ventricular Systolic Volume Pre and Post Sildenafil
NCT03696758 (20) [back to overview]	Right Ventricular Stroke Volume Pre and Post Metoprolol
NCT04425902 (171) [back to overview]	Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
NCT04425902 (171) [back to overview]	Treatment C: Change From Baseline in Albumin, Globulin, Protein
NCT04425902 (171) [back to overview]	Treatment C: Change From Baseline in Amylase, Lipase
NCT04425902 (171) [back to overview]	Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
NCT04425902 (171) [back to overview]	Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
NCT04425902 (171) [back to overview]	Treatment C: Change From Baseline in Erythrocytes
NCT04425902 (171) [back to overview]	Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin
NCT04425902 (171) [back to overview]	Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Volume
NCT04425902 (171) [back to overview]	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
NCT04425902 (171) [back to overview]	Treatment C: Change From Baseline in Hematocrit
NCT04425902 (171) [back to overview]	Treatment C: Change From Baseline in Hemoglobin
NCT04425902 (171) [back to overview]	Treatment C: Change From Baseline in Oral Temperature
NCT04425902 (171) [back to overview]	Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
NCT04425902 (171) [back to overview]	Treatment C: Change From Baseline in Pulse Rate
NCT04425902 (171) [back to overview]	Treatment C: Change From Baseline in Respiratory Rate
NCT04425902 (171) [back to overview]	Treatment C: Change From Baseline in SBP and DBP
NCT04425902 (171) [back to overview]	Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
NCT04425902 (171) [back to overview]	Treatment B: Absolute Values of Albumin, Globulin, Protein
NCT04425902 (171) [back to overview]	Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
NCT04425902 (171) [back to overview]	Treatment A: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
NCT04425902 (171) [back to overview]	Treatment A: Change From Baseline in SBP and DBP
NCT04425902 (171) [back to overview]	Treatment B: Absolute Values of Amylase, Lipase
NCT04425902 (171) [back to overview]	Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
NCT04425902 (171) [back to overview]	Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
NCT04425902 (171) [back to overview]	Treatment A: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
NCT04425902 (171) [back to overview]	Treatment A: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
NCT04425902 (171) [back to overview]	Treatment A: Change From Baseline in Amylase, Lipase
NCT04425902 (171) [back to overview]	Treatment A: Change From Baseline in Albumin, Globulin, Protein
NCT04425902 (171) [back to overview]	Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
NCT04425902 (171) [back to overview]	Treatment A: Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
NCT04425902 (171) [back to overview]	Treatment A: Absolute Values of Respiratory Rate
NCT04425902 (171) [back to overview]	Treatment A: Absolute Values of Pulse Rate
NCT04425902 (171) [back to overview]	Treatment B: Absolute Values of Respiratory Rate
NCT04425902 (171) [back to overview]	Treatment A: Absolute Values of Oral Temperature
NCT04425902 (171) [back to overview]	Treatment A: Absolute Values of Hemoglobin
NCT04425902 (171) [back to overview]	Treatment A: Absolute Values of Hematocrit
NCT04425902 (171) [back to overview]	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
NCT04425902 (171) [back to overview]	Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Volume
NCT04425902 (171) [back to overview]	Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin
NCT04425902 (171) [back to overview]	AUC(0-infinity) for Omeprazole
NCT04425902 (171) [back to overview]	Apparent Terminal Phase Half-life (t1/2) for Caffeine
NCT04425902 (171) [back to overview]	Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Time t (AUC[0-t]) for Caffeine
NCT04425902 (171) [back to overview]	AUC From Time Zero Extrapolated to Infinity (AUC[0-infinity]) for Caffeine
NCT04425902 (171) [back to overview]	AUC(0-infinity) for 1-hydroxymidazolam
NCT04425902 (171) [back to overview]	AUC(0-infinity) for 36-hydroxymontelukast
NCT04425902 (171) [back to overview]	AUC(0-infinity) for 5-hydroxyomeprazole
NCT04425902 (171) [back to overview]	Treatment A: Absolute Values of Erythrocytes
NCT04425902 (171) [back to overview]	Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase
NCT04425902 (171) [back to overview]	Treatment A: Absolute Values of Amylase, Lipase
NCT04425902 (171) [back to overview]	Treatment A: Absolute Values of Albumin, Globulin, Protein
NCT04425902 (171) [back to overview]	Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)
NCT04425902 (171) [back to overview]	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
NCT04425902 (171) [back to overview]	Treatment C: Tmax for GSK3640254
NCT04425902 (171) [back to overview]	Treatment C: t1/2 for GSK3640254
NCT04425902 (171) [back to overview]	Treatment C: Plasma Concentration at the End of the Dosing Interval (Ctau) for GSK3640254
NCT04425902 (171) [back to overview]	Treatment C: Cmax for GSK3640254
NCT04425902 (171) [back to overview]	Treatment C: AUC(0-t) for GSK3640254
NCT04425902 (171) [back to overview]	Treatment C: AUC From Time Zero to the End of the Dosing Interval at Steady State (AUC[0-tau]) for GSK3640254
NCT04425902 (171) [back to overview]	Treatment B: Change From Baseline in Respiratory Rate
NCT04425902 (171) [back to overview]	Treatment B: Change From Baseline in Pulse Rate
NCT04425902 (171) [back to overview]	AUC(0-infinity) for Alpha-hydroxymetoprolol
NCT04425902 (171) [back to overview]	AUC(0-infinity) for Digoxin
NCT04425902 (171) [back to overview]	AUC(0-infinity) for Flurbiprofen
NCT04425902 (171) [back to overview]	Treatment B: Change From Baseline in Oral Temperature
NCT04425902 (171) [back to overview]	Treatment B: Change From Baseline in Hemoglobin
NCT04425902 (171) [back to overview]	Treatment B: Change From Baseline in Hematocrit
NCT04425902 (171) [back to overview]	Treatment B: Change From Baseline in Erythrocytes Mean Corpuscular Volume
NCT04425902 (171) [back to overview]	Treatment B: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin
NCT04425902 (171) [back to overview]	Treatment B: Change From Baseline in Erythrocytes
NCT04425902 (171) [back to overview]	AUC(0-infinity) for Metoprolol
NCT04425902 (171) [back to overview]	AUC(0-infinity) for Midazolam
NCT04425902 (171) [back to overview]	AUC(0-infinity) for Montelukast
NCT04425902 (171) [back to overview]	AUC(0-infinity) for Pravastatin
NCT04425902 (171) [back to overview]	AUC(0-t) for 1-hydroxymidazolam
NCT04425902 (171) [back to overview]	AUC(0-t) for 36-hydroxymontelukast
NCT04425902 (171) [back to overview]	AUC(0-t) for 5-hydroxyomeprazole
NCT04425902 (171) [back to overview]	AUC(0-t) for Alpha-hydroxymetoprolol
NCT04425902 (171) [back to overview]	AUC(0-t) for Digoxin
NCT04425902 (171) [back to overview]	AUC(0-t) for Flurbiprofen
NCT04425902 (171) [back to overview]	AUC(0-t) for Metoprolol
NCT04425902 (171) [back to overview]	AUC(0-t) for Midazolam
NCT04425902 (171) [back to overview]	AUC(0-t) for Montelukast
NCT04425902 (171) [back to overview]	AUC(0-t) for Omeprazole
NCT04425902 (171) [back to overview]	AUC(0-t) for Pravastatin
NCT04425902 (171) [back to overview]	Cmax for 1-hydroxymidazolam
NCT04425902 (171) [back to overview]	Cmax for 36-hydroxymontelukast
NCT04425902 (171) [back to overview]	Cmax for 5-hydroxyomeprazole
NCT04425902 (171) [back to overview]	Cmax for Alpha-hydroxymetoprolol
NCT04425902 (171) [back to overview]	Cmax for Digoxin
NCT04425902 (171) [back to overview]	Cmax for Flurbiprofen
NCT04425902 (171) [back to overview]	Cmax for Metoprolol
NCT04425902 (171) [back to overview]	Cmax for Midazolam
NCT04425902 (171) [back to overview]	Cmax for Montelukast
NCT04425902 (171) [back to overview]	Cmax for Omeprazole
NCT04425902 (171) [back to overview]	Cmax for Pravastatin
NCT04425902 (171) [back to overview]	Maximum Observed Plasma Concentration (Cmax) for Caffeine
NCT04425902 (171) [back to overview]	Ratio of AUC(0-infinity) of 1-hydroxymidazolam to Midazolam
NCT04425902 (171) [back to overview]	Ratio of AUC(0-infinity) of 36-hydroxymontelukast to Montelukast
NCT04425902 (171) [back to overview]	Ratio of AUC(0-infinity) of 5-hydroxyomeprazole to Omeprazole
NCT04425902 (171) [back to overview]	Ratio of AUC(0-infinity) of Alpha-hydroxymetoprolol to Metoprolol
NCT04425902 (171) [back to overview]	Ratio of Cmax of 1-hydroxymidazolam to Midazolam
NCT04425902 (171) [back to overview]	Ratio of Cmax of 36-hydroxymontelukast to Montelukast
NCT04425902 (171) [back to overview]	Ratio of Cmax of 5-hydroxyomeprazole to Omeprazole
NCT04425902 (171) [back to overview]	Ratio of Cmax of Alpha-hydroxymetoprolol to Metoprolol
NCT04425902 (171) [back to overview]	t1/2 for 1-hydroxymidazolam
NCT04425902 (171) [back to overview]	Treatment B: Absolute Values of Oral Temperature
NCT04425902 (171) [back to overview]	Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
NCT04425902 (171) [back to overview]	Treatment B: Absolute Values of Pulse Rate
NCT04425902 (171) [back to overview]	Treatment B: Absolute Values of SBP and DBP
NCT04425902 (171) [back to overview]	Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
NCT04425902 (171) [back to overview]	Treatment B: Change From Baseline in Albumin, Globulin, Protein
NCT04425902 (171) [back to overview]	Treatment B: Change From Baseline in Amylase, Lipase
NCT04425902 (171) [back to overview]	Tmax for 5-hydroxyomeprazole
NCT04425902 (171) [back to overview]	Treatment B: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
NCT04425902 (171) [back to overview]	Treatment B: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
NCT04425902 (171) [back to overview]	Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
NCT04425902 (171) [back to overview]	Treatment A: Change From Baseline in Respiratory Rate
NCT04425902 (171) [back to overview]	Treatment A: Change From Baseline in Pulse Rate
NCT04425902 (171) [back to overview]	Treatment A: Change From Baseline in Oral Temperature
NCT04425902 (171) [back to overview]	Treatment A: Change From Baseline in Hemoglobin
NCT04425902 (171) [back to overview]	Treatment A: Change From Baseline in Hematocrit
NCT04425902 (171) [back to overview]	Treatment A: Change From Baseline in Erythrocytes Mean Corpuscular Volume
NCT04425902 (171) [back to overview]	Treatment A: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin
NCT04425902 (171) [back to overview]	Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
NCT04425902 (171) [back to overview]	Treatment A: Change From Baseline in Erythrocytes
NCT04425902 (171) [back to overview]	Tmax for Pravastatin
NCT04425902 (171) [back to overview]	Treatment B: Change From Baseline in SBP and DBP
NCT04425902 (171) [back to overview]	Treatment B: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
NCT04425902 (171) [back to overview]	Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
NCT04425902 (171) [back to overview]	Treatment C: Absolute Values of Albumin, Globulin, Protein
NCT04425902 (171) [back to overview]	Treatment C: Absolute Values of Amylase, Lipase
NCT04425902 (171) [back to overview]	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
NCT04425902 (171) [back to overview]	Treatment C: Absolute Values of Erythrocytes
NCT04425902 (171) [back to overview]	Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
NCT04425902 (171) [back to overview]	Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin
NCT04425902 (171) [back to overview]	Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Volume
NCT04425902 (171) [back to overview]	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
NCT04425902 (171) [back to overview]	Treatment C: Absolute Values of Hematocrit
NCT04425902 (171) [back to overview]	Treatment C: Absolute Values of Hemoglobin
NCT04425902 (171) [back to overview]	Treatment C: Absolute Values of Oral Temperature
NCT04425902 (171) [back to overview]	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
NCT04425902 (171) [back to overview]	Treatment C: Absolute Values of Pulse Rate
NCT04425902 (171) [back to overview]	Tmax for Omeprazole
NCT04425902 (171) [back to overview]	Tmax for Montelukast
NCT04425902 (171) [back to overview]	Tmax for Midazolam
NCT04425902 (171) [back to overview]	Tmax for Metoprolol
NCT04425902 (171) [back to overview]	Tmax for Flurbiprofen
NCT04425902 (171) [back to overview]	Tmax for Digoxin
NCT04425902 (171) [back to overview]	Tmax for Alpha-hydroxymetoprolol
NCT04425902 (171) [back to overview]	Tmax for 36-hydroxymontelukast
NCT04425902 (171) [back to overview]	Tmax for 1-hydroxymidazolam
NCT04425902 (171) [back to overview]	Time to Cmax (Tmax) for Caffeine
NCT04425902 (171) [back to overview]	t1/2 for Pravastatin
NCT04425902 (171) [back to overview]	t1/2 for Omeprazole
NCT04425902 (171) [back to overview]	t1/2 for Montelukast
NCT04425902 (171) [back to overview]	t1/2 for Midazolam
NCT04425902 (171) [back to overview]	t1/2 for Metoprolol
NCT04425902 (171) [back to overview]	t1/2 for Flurbiprofen
NCT04425902 (171) [back to overview]	t1/2 for Digoxin
NCT04425902 (171) [back to overview]	t1/2 for Alpha-hydroxymetoprolol
NCT04425902 (171) [back to overview]	t1/2 for 5-hydroxyomeprazole
NCT04425902 (171) [back to overview]	t1/2 for 36-hydroxymontelukast
NCT04425902 (171) [back to overview]	Treatment C: Absolute Values of Respiratory Rate
NCT04425902 (171) [back to overview]	Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
NCT04425902 (171) [back to overview]	Treatment B: Absolute Values of Erythrocytes
NCT04425902 (171) [back to overview]	Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin
NCT04425902 (171) [back to overview]	Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Volume
NCT04425902 (171) [back to overview]	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
NCT04425902 (171) [back to overview]	Treatment B: Absolute Values of Hematocrit
NCT04425902 (171) [back to overview]	Treatment B: Absolute Values of Hemoglobin
NCT04425902 (171) [back to overview]	Treatment C: Absolute Values of SBP and DBP
NCT04767061 (10) [back to overview]	Change in Patient-reported Health Status When on Beta-blocker Versus When Off Beta-blocker, as Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ-12)
NCT04767061 (10) [back to overview]	Change in Exercise Capacity When on Beta-blocker Versus When Off Beta-blocker, as Measured by Peak Oxygen Consumption (VO2) During Cardiopulmonary Exercise Test (CPET)
NCT04767061 (10) [back to overview]	Change in Patient-reported Quality of Life When on Beta-blocker Versus When Off Beta-blocker, as Measured by Patient-Reported Outcome Measurement Information System-29 (PROMIS-29)
NCT04767061 (10) [back to overview]	Change in Physical Activity When on Beta-blocker Versus When Off Beta-blocker, as Measured by Step Count on Wearable Activity Monitoring Device
NCT04767061 (10) [back to overview]	Change in Patient-reported Sexual Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by Patient-Reported Outcome Measurement Information System-Sexual Function (PROMIS-Sexual Function)
NCT04767061 (10) [back to overview]	Change in Patient-reported Cognitive Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by Patient-Reported Outcome Measurement Information System-Short Form 6a (PROMIS SF-6a)
NCT04767061 (10) [back to overview]	Change in Lower Extremity Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by the Gait Speed Portion of a Modified Version of the Short Physical Performance Battery.
NCT04767061 (10) [back to overview]	Change in Lower Extremity Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by the Chair Rise Portion of a Modified Version of the Short Physical Performance Battery.
NCT04767061 (10) [back to overview]	Change in Lower Extremity Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by the Balance Portion of a Modified Version of the Short Physical Performance Battery.
NCT04767061 (10) [back to overview]	Change in Patient-reported Health When on Beta-blocker Versus When Off Beta-blocker, as Measured by the EuroQol-5D Visual Analogue System (EQ-5D VAS)

Stroke in the Blood Pressure Trial.

Time to first occurrence of nonfatal or fatal stroke among participants in the BP Trial. (NCT00000620)
Timeframe: 4.7 years

Intervention	participants (Number)
BP Trial: Intensive Control	36
BP Trial: Standard Control	62

Intervention	participants (Number)
Glycemia Trial: Intensive Control	503
Glycemia Trial: Standard Control	543

Intervention	mm Hg (Mean)
	Visit 1	Visit 2	Visit 3	Visit 4	Visit 5	Visit 6	Visit 7	Visit 8	Visit 9
1-NEB	-8.3	-8.4	-10.6	-12.1	-13.0	-14.5	-15.5	-16.3	-16.7
2-MET	-8.4	-8.4	-9.8	-10.7	-12.4	-12.1	-13.1	-12.4	-13.7

Intervention	units on a scale (Mean)
Comprehensive Intervention Group	2.9
Less Intensive Intervention Group	1.8

Intervention	mmHg (Mean)
Comprehensive Intervention Group	130.8
Less Intensive Intervention Group	135.9

Intervention	mg/dL (Mean)
Comprehensive Intervention Group	100.1
Less Intensive Intervention Group	110.6

Intervention	mm Hg (Number)
	Systolic Blood Pressure	Diastolic Blood Pressure
Coreg CR	-15.90	-10.89
Toprol XL	-16.23	-11.06

Intervention	mg/dL (Number)
	Total Serum Cholesterol	Low-Density Lipoprotein (LDL)	Low+Very Low Density Lipoprotein	High-Density Lipoprotein 2 (HDL2)	High-Density Lipoprotein 3 (HDL3)	Low-Density Lipoprotein-Relative Flotation	Intermediate Density Lipoproteins+VLDL
Coreg CR	0.1	-1.1	0.9	-1.45	-4.0	0.166	2.0
Toprol XL	-0.7	-1.7	0.4	-6.5	-3.5	-1.360	5.6

Intervention	g/L (Number)
	Apolipoprotein A-1 (Apo-A1)	Apolipoprotein B (Apo-B)
Coreg CR	-1.82	-1.16
Toprol XL	-3.45	0.81

Intervention	Participants (Count of Participants)
Additional Epinephrine Doses	0
Metoprolol Instead of Additional Epinephrine Doses	0

Intervention	Participants (Count of Participants)
Additional Doses of Epinephrine	0
Metoprolol Instead of Additional Epinephrine Doses	0

Intervention	ng/mL/h (Number)
	Screening	Week 4	Week 6	Week 7	Week 9	Week 10	Week 11	Week 12
Aliskiren and Metoprolol	2.07	1.22	0.28	0.18	0.28	0.07	0.03	0.06

Intervention	mm Hg (Number)
	Week 1-Systolic	Week 1-Diastolic	Week 2-Systolic	Week 2-Diastolic	Week 3-Systolic	Week 3-Diastolic	Week 4-Systolic	Week 4-Diastolic	Week 5-Systolic	Week 5-Diastolic	Week 6-Systolic	Week 6-Diastolic	Week 7-Systolic	Week 7-Diastolic	Week 8-Systolic	Week 8-Diastolic	Week 9-Systolic	Week 9 -Diastolic	Week 10-Systolic	Week 10-Diastolic	Week 11-Systolic	Week 11-Diastolic	Week 12-Systolic	Week 12-Diastolic
Aliskiren and Metoprolol	146	64	144	88	148	90	148	92	156	92	150	84	157	89	147	76	129	94	139	79	170	90	146	78

Intervention	pg/mL (Number)
	Week 5	Week 6	Week 7	Week 9	Week 10	Week 11	Week 12
Aliskiren and Metoprolol	16.5	13.5	20.5	22	2.7	4.4	3.2

Intervention	participants (Number)
Intensive Blood-Pressure Lowering	719
Guideline-Recommended Blood-Pressure Lowering	785

Intervention	Unit on a scale (Mean)
Nebivolol	0.011
Metoprolol ER	1.156
Hydrochlorothiazide (HCTZ)	-0.662

Intervention	Percentage (Mean)
Nebivolol	0.12
Metoprolol ER	0.00
Hydrochlorothiazide (HCTZ)	0.40

Intervention	percent (%) (Mean)
	Augmentation index at Baseline	Augmentation index at 26 Weeks
Metoprolol	26.2	24.6
Nebivolol	22.0	22.1

Intervention	mmHg (Mean)
	Aortic Systolic Blood Pressure at Baseline	Aortic Systolic Blood Pressure at 26 Weeks
Metoprolol	127.8	123.8
Nebivolol	125.3	121.6

Intervention	ratio (Mean)
	Pulse pressure amplification at Baseline	Pulse pressure amplification at 26 Weeks
Metoprolol	0.79	0.85
Nebivolol	0.77	0.83

Intervention	m/s (Mean)
	Pulse wave velocity at Baseline	Pulse wave velocity at 26 Weeks
Metoprolol	6.52	6.4
Nebivolol	6.48	6.3

metoprolol

Description

Cross-References

Synonyms (142)

Research Excerpts

Overview

Effects

Actions

Treatment

Toxicity

Pharmacokinetics

Compound-Compound Interactions

Bioavailability

Dosage Studied

Roles (5)

Drug Classes (4)

Pathways (1)

Protein Targets (41)

Potency Measurements

Inhibition Measurements

Activation Measurements

Other Measurements

Biological Processes (119)

Molecular Functions (69)

Ceullar Components (30)

Bioassays (385)

Research

Studies (5,534)

Market Indicators

Research Demand Index: 139.02

Study Types

Clinical Trials (242)

Trial Overview

Trial Outcomes

Stroke in the Blood Pressure Trial.

First Occurrence of MCE or Revascularization or Hospitalization for Congestive Heart Failure (CHF) in Lipid Trial.

First Occurrence of Major Cardiovascular Event (MCE) in the Blood Pressure Trial.

First Occurrence of a Major Cardiovascular Event (MCE); Specifically Nonfatal Heart Attack, Nonfatal Stroke, or Cardiovascular Death (Measured Throughout the Study) in the Glycemia Trial.

Death From Any Cause in the Glycemia Trial.

First Occurrence of Major Cardiovascular Event (MCE) in the Lipid Trial.

Flow Mediated Dilation

Change in Average Sitting Diastolic Blood Pressure (DBP) Taken at Trough at the End of Treatment Compared to Baseline

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline

Patients' Satisfaction With Care and Health Care Utilization

Systolic Blood Pressure

HbA1c

Low-density Lipoprotein Cholesterol

Blood Pressure Response (Delta BP (After 18 Weeks of Medication - Baseline)).

Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) Levels by Treatment Group at Maintenance Month 6

Change From Baseline in Hemoglobin A1c (HbA1c) (Glycemic Parameter) by Treatment Group at Maintenance Month 6

Change From Baseline in c-Peptide (Glycemic Parameter) by Treatment Group at Maintenance Month 6

Change From Baseline in Fasting Insulin (Glycemic Parameter) by Treatment Group at Maintenance Month 6

Change From Baseline in Log Transformed Lipoprotein-associated Phospholipase A2 (LpPLA2) by Treatment Group at Maintenance Month 6

Change From Baseline in Blood Pressure by Treatment Group at Maintenance Month 6

Change From Baseline in Fasting Plasma Glucose (FPG) (Glycemic Parameter) by Treatment Group at Maintenance Month 6

Change From Baseline in Additional Lipid Parameters by Treatment Group With Unit of Measures of mg/dL at Maintenance Month 6

Change From Baseline in Additional Lipid Parameters by Treatment Group With Unit of Measures of g/L at Maintenance Month 6

Change From Baseline in Weight by Treatment Group at Maintenance Month

Change From Baseline in Triglycerides Levels by Treatment Group at Maintenance Month 6

Change From Baseline in Heart Rate by Treatment Group at Maintenance Month 6

Change From Baseline in Log Transformed High Sensitivity C-reactive Protein (Hs-CRP) by Treatment Group at Maintenance Month 6

Change From Baseline in Homeostasis Model Assessment (Glycemic Parameter) by Treatment Group at Maintenance Month 6

Plasma B-type Natriuretic Peptide (BNP) at Baseline

Plasma B-type Natriuretic Peptide (BNP) at 6 Months

Plasma B-type Natriuretic Peptide (BNP)

Baseline Left Ventricular Ejection Fraction by Magnetic Resonance Imaging (MRI)

Change in Left Ventricular Ejection Fraction by Magnetic Resonance Imaging (MRI)%

Left Ventricular Ejection Fraction by Magnetic Resonance Imaging (MRI)at 6 Months

Composite Value of 3 Variables After 9 Months: Cardiovascular Death (Days Alive), Cardiovascular Hospitalization (Days Out of Hospital), Heart Failure Symptoms (Symptom Score Subset of the Kansas City Cardiomyopathy Questionnaire - Questions 3,5,7,9)

Discontinuations

Number of CV Deaths

Number of Days in Hospital for CV Reason

Total Number of Titration Steps in Prescribed Heart Failure Treatment

Changes in Health-related Quality of Life

Changes in Heart Failure Symptoms

Changes in NT-proBNP Values Over Time in All Patients

Survival to Hospital Discharge

Adverse Effects

Return of Spontaneous Circulation

Intervention	mm HG (Mean)
	SBP ABPM on metoprolol	DBP ABPM on metoprolol	SBP ABPM on nebivolol	DBP ABPM on nebivolol
Metoprolol to Nebivolol	122	72	122	71

Intervention	Participants (Count of Participants)
Amiodarone - Yes	50
Amiodarone - No	56
Ascorbic Acid - Yes	58
Ascorbic Acid - No	48

Intervention	Participants (Count of Participants)
Beta Blockers, Ascorbic Acid and Amiodarone	1
Beta Blockers and Ascorbic Acid	1
Beta Blockers and Amiodarone	1
Beta Blockers Alone	0

Intervention	millimole/Liter (mmol/L) (Mean)
Placebo	-0.07
LY377604 (75 mg)	-0.03
Sibutramine (30 mg)/Metoprolol (200 mg)	0.00
LY377604 (15 mg)/Sibutramine (30 mg)	-0.00
LY377604 (40 mg)/Sibutramine (30 mg)	-0.07
LY377604 (75 mg)/Sibutramine (30 mg)	0.16
LY377604 (75 mg)/Sibutramine (15 mg)	-0.16

Intervention	kilograms (kg) (Least Squares Mean)
	Fat Mass	Lean Mass
LY377604 (15 mg)/Sibutramine (30 mg)	-6.13	-1.85
LY377604 (40 mg)/Sibutramine (30 mg)	-4.80	-0.71
LY377604 (75 mg)	0.54	0.15
LY377604 (75 mg)/Sibutramine (15 mg)	-2.55	-1.48
LY377604 (75 mg)/Sibutramine (30 mg)	-4.29	-1.08
Placebo	-2.40	-0.55
Sibutramine (30 mg)/Metoprolol (200 mg)	-3.00	-1.92

Intervention	kilograms (Least Squares Mean)
Placebo	-2.37
LY377604 (75 mg)	0.45
Sibutramine (30 mg)/Metoprolol (200 mg)	-6.41
LY377604 (15 mg)/Sibutramine (30 mg)	-8.15
LY377604 (40 mg)/Sibutramine (30 mg)	-6.49
LY377604 (75 mg)/Sibutramine (30 mg)	-7.06
LY377604 (75 mg)/Sibutramine (15 mg)	-4.68

Intervention	percentage of participants (Number)
Placebo	10.2
LY377604 (75 mg)	0.0
Sibutramine (30 mg)/Metoprolol (200 mg)	18.8
LY377604 (15 mg)/Sibutramine (30 mg)	34.7
LY377604 (40 mg)/Sibutramine (30 mg)	21.2
LY377604 (75 mg)/Sibutramine (30 mg)	18.0
LY377604 (75 mg)/Sibutramine (15 mg)	6.5

Intervention	percent change (Least Squares Mean)
Placebo	-5.86
LY377604 (75 mg)	-2.22
Sibutramine (30 mg)/Metoprolol (200 mg)	-7.55
LY377604 (15 mg)/Sibutramine (30 mg)	-5.96
LY377604 (40 mg)/Sibutramine (30 mg)	-3.02
LY377604 (75 mg)/Sibutramine (30 mg)	-3.11
LY377604 (75 mg)/Sibutramine (15 mg)	-7.29

Intervention	percent change (Least Squares Mean)
Placebo	-2.21
LY377604 (75 mg)	0.48
Sibutramine (30 mg)/Metoprolol (200 mg)	-6.12
LY377604 (15 mg)/Sibutramine (30 mg)	-8.53
LY377604 (40 mg)/Sibutramine (30 mg)	-6.61
LY377604 (75 mg)/Sibutramine (30 mg)	-7.05
LY377604 (75 mg)/Sibutramine (15 mg)	-4.71

Intervention	centimeter (cm) (Least Squares Mean)
Placebo	-6.58
LY377604 (75 mg)	-2.51
Sibutramine (30 mg)/Metoprolol (200 mg)	-8.84
LY377604 (15 mg)/Sibutramine (30 mg)	-6.76
LY377604 (40 mg)/Sibutramine (30 mg)	-3.57
LY377604 (75 mg)/Sibutramine (30 mg)	-3.55
LY377604 (75 mg)/Sibutramine (15 mg)	-8.67