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tolbutamide

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Description

Tolbutamide: A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290) [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

tolbutamide : An N-sulfonylurea that consists of 1-butylurea having a tosyl group attached at the 3-position. [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]

Cross-References

ID SourceID
PubMed CID5505
CHEMBL ID782
CHEBI ID27999
SCHEMBL ID15918
MeSH IDM0021630

Synonyms (296)

Synonym
nsc-87833
AC-12490
BIDD:PXR0179
CBIOL_001920
MLS001148399
MLS002152944
AB00052110-16
BRD-K85119730-001-06-5
n-[(butylamino)carbonyl]-4-methylbenzenesulfonamide
tolbutamidum
orinase (tn)
tolbutamida
CHEBI:27999 ,
n-(p-methylbenzenesulfonyl)-n'-butylurea
smr000058363
1-butyl-3-(p-tolylsulfonyl)urea
orabet
toluvan
diabuton
nci-c01763
rastinon
3-(p-tolyl-4-sulfonyl)-1-butylurea
toluina
arkozal
d 860
glyconon
oterben
n-butyl-n'-p-toluenesulfonylurea
oralin
n-(4-methylbenzenesulfonyl)-n'-butylurea
n-(4-methylphenylsulfonyl)-n'-butylurea
artosin
nsc-23813
1-butyl-3-tosylurea
artozin
tolbutamid
orezan
mobenol
n-butyl-n'-(p-tolylsulfonyl)urea
diasulfon
pramidex
n-butyl-n'-(4-methylphenylsulfonyl)urea
dolipol
nsc23813
tolylsulfonylbutylurea
orinaz
n-(sulfonyl-p-methylbenzene)-n'-n-butylurea
1-butyl-3-(p-methylphenylsulfonyl)urea
dirastan
orinase
aglicid
tolbusal
1-p-toluenesulfonyl-3-butylurea
wln: 4mvmswr d1
diaben
drabet
urea, 1-butyl-3-(p-tolylsulfonyl)-
n-n-butyl-n'-tosylurea
ipoglicone
diabetamid
benzenesulfonamide, n-[(butylamino)carbonyl]-4-methyl-
n-butyl-n'-toluene-p-sulfonylurea
willbutamide
butamid
diabetol
n-(p-tolylsulfonyl)-n'-butylcarbamide
hls 831
tolumid
butamide
KBIO1_000341
DIVK1C_000341
EU-0101154
SPECTRUM_000447
BSPBIO_002078
BPBIO1_000131
PRESTWICK_471
BIO2_000227
BIO2_000707
lopac-t-0891
BIO1_001184
NCGC00015999-01
cas-64-77-7
BIO1_000206
BIO1_000695
NCGC00015999-02
SPECTRUM5_001272
PRESTWICK3_000190
BSPBIO_000119
CMAP_000008
IDI1_033977
IDI1_000341
BSPBIO_001507
NCGC00022721-03
BIM-0051121.0001
AB00052110
diabesan
arcosal
einecs 200-594-3
butamidum
nsc 23813
hsdb 3393
beglucin
n-((butylamino)carbonyl)-4-methylbenzenesulfonamide
tolbutamidum [inn-latin]
toluran
n-4-methylbenzolsulfonyl-n-butylurea
tarasina
tolbutamida [inn-spanish]
brn 1984428
ccris 592
benzenesulfonamide, n-((butylamino)carbonyl)-4-methyl-
sk-tolbutamide
u 2043
n-4-(methylbenzolsulfonyl)-n-butylurea
n-(sulfonyl-p-methylbenzene)-n'-butylurea
tolbet
tolbutone
C07148
tolbutamide
64-77-7
DB01124
D00380
tolbutamide (jp17/usp/inn)
LOPAC0_001154
NCGC00022721-07
NCGC00022721-08
NCGC00022721-09
NCGC00022721-05
MLS000028399 ,
KBIO2_004843
KBIOGR_002275
KBIOSS_000227
KBIO3_000454
KBIO2_002795
KBIOSS_002276
KBIO2_002275
KBIO3_001578
KBIO3_002755
KBIO3_000453
KBIO2_000927
KBIOSS_000927
KBIO2_005363
KBIO2_007411
KBIO2_003495
KBIOGR_000227
KBIO2_006063
KBIOGR_000795
KBIO2_000227
NCIOPEN2_009592
SPECTRUM4_000358
PRESTWICK1_000190
SPBIO_002040
SPECTRUM3_000599
NINDS_000341
SPBIO_001000
PRESTWICK0_000190
SPECTRUM2_001210
SPECTRUM1500581
PRESTWICK2_000190
NCGC00015999-03
NCGC00022721-06
NCGC00022721-10
NCGC00022721-04
NCGC00015999-07
HMS2089C17
HMS2092M21
T 0891 ,
HMS1989L09
NCGC00015999-14
CHEMBL782 ,
HMS1361L09
HMS1791L09
HMS501B03
HMS1568F21
1-butyl-3-(4-methylphenyl)sulfonylurea
n-butyl-n''-(p-tolylsulfonyl)urea
bdbm50027886
n-(4-methylphenylsulfonyl)-n''-butylurea
n-n-butyl-n''-tosylurea
n-butyl-n''-(4-methylphenylsulfonyl)urea
NCGC00015999-10
A834879
n'-butyl-n-(p-tolylsulfonyl)carbamimidate;tolbutamide
1-butyl-3-(4-methylphenylsulfonyl)urea
HMS3259A08
HMS3263H09
HMS2095F21
dtxcid801359
tox21_302795
dtxsid8021359 ,
NCGC00256548-01
NCGC00259161-01
tox21_201612
pharmakon1600-01500581
nsc-757354
nsc757354
tox21_110279
3-butyl-1-[(4-methylbenzene)sulfonyl]urea
HMS2232H16
unii-982xcm1foi
4-11-00-00396 (beilstein handbook reference)
tolbutamide [usp:inn:ban:jan]
982xcm1foi ,
CCG-39141
NCGC00015999-16
NCGC00015999-06
NCGC00015999-05
NCGC00015999-08
NCGC00015999-15
NCGC00015999-09
NCGC00015999-17
NCGC00015999-12
NCGC00015999-13
NCGC00015999-11
NCGC00015999-04
3-butyl-1-(4-methylbenzenesulfonyl)urea
FT-0603265
LP01154
AKOS015894999
S2443
gtpl6848
tolbutamidum [who-ip latin]
tolbutamide [jan]
tolbutamide [usp monograph]
tolbutamide [who-dd]
tolbutamide [who-ip]
tolbutamide [ep monograph]
tolbutamide [orange book]
tolbutamide [mart.]
tolbutamide [mi]
tolbutamide [vandf]
tolbutamide [usp-rs]
tolbutamide [inn]
tolbutamide [hsdb]
HY-B0401
NC00543
SCHEMBL15918
NCGC00015999-19
tox21_110279_1
T3690
n-(butylcarbamoyl)-4-methylbenzenesulfonamide
tox21_501154
NCGC00261839-01
W-104820
n-(n-butyl)-n'-p-toluene-sulfonylurea
tolumide
1-(([(butylamino)carbonyl]amino)sulfonyl)-4-methylbenzene #
1-butyl-3-(para-tolylsulfonyl)-urea
u-2043
1-butyl-3-(4-methylbenzenesulfonyl)urea
HMS3402L09
OPERA_ID_112
AB00052110_18
AB00052110_17
mfcd00027169
SR-01000003059-2
sr-01000003059
tolbutamide, vetranal(tm), analytical standard
tolbutamide, united states pharmacopeia (usp) reference standard
Z44591715
HMS3651N03
tolbutamide, analytical standard
tolbutamide, european pharmacopoeia (ep) reference standard
tolbutamide 1.0 mg/ml in acetonitrile
SR-01000003059-7
SR-01000003059-4
SBI-0051121.P003
HMS3712F21
SW196681-3
Q414275
tolbutamide il
tolbutamide form i^l^
tolbutamide iii
tolbutamide form i^h^
nsc-813220
nsc813220
AS-14136
BCP09192
BRD-K85119730-001-17-2
EN300-124678
SDCCGSBI-0051121.P004
NCGC00015999-29
D87667
NCGC00015999-20
tolbutamide (usp-rs)
v04ca01
a10bb03
tolbutamidum (inn-latin)
tolbutamide (mart.)
n-(p-tolylsulfonyl)n'-butylcarbamide
n'-4-methylbenzenesulfonyl-n''-butylurea
tolbutamide (usp monograph)
tolbutamide (ep monograph)
tolbutamide (usp:inn:ban:jan)
tolbutamida (inn-spanish)
SY014891

Research Excerpts

Overview

Tolbutamide (TBM) is an oral hypoglycemic drug largely used in the treatment of type II Mellitus diabetes. Tolbutamide is an important member of the sulfonylureas, drugs which stimulate secretion of several hormones, including insulin and prolactin.

ExcerptReferenceRelevance
"Tolbutamide (TBM) is an oral hypoglycemic drug largely used in the treatment of type II Mellitus diabetes."( Structural, thermal, vibrational, solubility and DFT studies of a tolbutamide co-amorphous drug delivery system for treatment of diabetes.
de Sousa, FF; Lage, MR; Lima, ADDSG; Lopes, JA; R Sá, M; Ribeiro, PRS; Sarraguça, JMG; Sarraguça, MSC, 2022
)
1.68
"Tolbutamide is an oral anti-hyperglycaemic agent used to treat non-insulin-dependent diabetes mellitus with species-dependent metabolic profiles. "( Methyl-hydroxylation and subsequent oxidation to produce carboxylic acid is the major metabolic pathway of tolbutamide in chimeric TK-NOG mice transplanted with human hepatocytes.
Higuchi, Y; Suemizu, H; Uehara, S; Yamazaki, H; Yoneda, N, 2021
)
2.28
"Tolbutamide is a better CYP2C9 probe than flurbiprofen and losartan, and the 0- to 12-hour amount of 4'-hydroxytolbutamide and carboxytolbutamide is the best urinary measure of its metabolism."( Tolbutamide, flurbiprofen, and losartan as probes of CYP2C9 activity in humans.
Blaisdell, JA; Frye, RF; Goldstein, JA; Hinderliter, AL; Lee, CR; Pieper, JA, 2003
)
2.48
"Tolbutamide is an oral hypoglycemic agent that exists in four polymorphic forms."( Crystal forms of tolbutamide from acetonitrile and 1-octanol: effect of solvent, humidity and compression pressure.
Alexander, KS; Chakravarty, P; Chatterjee, K; Riga, AT, 2005
)
1.39
"Tolbutamide is an important member of the sulfonylureas, drugs which stimulate secretion of several hormones, including insulin and prolactin (PRL), through a mechanism postulated to involve blocking ATP-sensitive K+ channels. "( Evidence that tolbutamide induces prolactin secretion by a mechanism which does not involve blocking ATP-sensitive potassium channels.
Greer, MA; Greer, SE; Sato, N; Wang, X, 1994
)
2.09
"Tolbutamide (TOLB) is a sulfonylurea used to treat non-insulin-dependent diabetes mellitus and is a suspected teratogen. "( The effect of tolbutamide on rat embryonic development in vitro.
Grafton, TF; Hansen, DK; Ziegler, MH, 1993
)
2.09
"Tolbutamide is a sulfonylurea oral hypoglycaemic agent with suspected teratogenicity in humans and demonstrated teratogenicity in laboratory animals, but the underlying mechanism is unknown. "( Tolbutamide: placental transfer, tissue distribution, and metabolic effects in murine embryos.
Emanuel, AN; Smoak, IW, 1998
)
3.19
"Tolbutamide is a sulfonylurea-type oral hypoglycemic agent whose action is terminated by hydroxylation of the tolylsulfonyl methyl moiety catalyzed by cytochrome P-450 (CYP) enzymes of the human CYP2C subfamily. "( CYP2C19 participates in tolbutamide hydroxylation by human liver microsomes.
Johnson, EF; Lasker, JM; Raucy, JL; Wester, MR, 2000
)
2.06
"Tolbutamide is a sulfonylurea oral hypoglycemic agent widely used for the treatment of non insulin-dependent diabetes mellitus. "( Tolbutamide alters glucose transport and metabolism in the embryonic mouse heart.
Smoak, IW, 2002
)
3.2

Effects

Tolbutamide has been used as a model drug for an examination of the effects of eleven substituted imidazole compounds on hepatic metabolism. Tolbutamide, which has no ketone group within its chemical structure, strongly inhibited the heart enzyme, whereas it had little ability to inhibit the liver or kidney enzyme.

ExcerptReferenceRelevance
"Tolbutamide has previously been shown to amplify the pressor effects of "exogenous" catecholamines in conscious dogs, possibly due to sensitization of the alpha 1-adrenoreceptor-mediated vasoconstriction. "( Potentiation of the pressor response to stress by tolbutamide in dogs.
Lee, KC; Randall, DC,
)
1.83
"Tolbutamide, which has no ketone group within its chemical structure, strongly inhibited the heart enzyme, whereas it had little ability to inhibit the liver or kidney enzyme."( Characterization of acetohexamide reductases purified from rabbit liver, kidney, and heart: structural requirements for substrates and inhibitors.
Akita, H; Imamura, Y; Koga, T; Migita, T; Nozawa, M; Otagiri, M; Ryu, A, 1997
)
1.02
"E.g. Tolbutamide metabolism has been shown to be inhibited by coumarole derivatives."( [Drug interaction during therapy with tolbutamide. The influence of some commonly used drugs on plasma level and half life in diabetic out-patients (author's transl)].
Grille, W; Johnsen, K; Kolenda, KD, 1979
)
0.99
"3. Tolbutamide, which has effects similar to glibenclamide in other tissues, paradoxically abolishes HPV, an effect reversed by glibenclamide."( Opposing actions of tolbutamide and glibenclamide on hypoxic pulmonary vasoconstriction.
Kozlowski, RZ; Nye, PC; Robertson, BE, 1992
)
1.12
"Tolbutamide hydroxylation has been investigated in human, rabbit and rat liver microsomes and by six purified forms of hepatic rabbit cytochromes P-450. "( Tolbutamide hydroxylation by human, rabbit and rat liver microsomes and by purified forms of cytochrome P-450.
Birkett, DJ; Laupattarakasem, P; McManus, ME; Miners, JO; Veronese, ME,
)
3.02
"Tolbutamide hydroxylation has been investigated in human liver microsomes. "( Tolbutamide hydroxylation by human liver microsomes. Kinetic characterisation and relationship to other cytochrome P-450 dependent xenobiotic oxidations.
Birkett, DJ; McManus, ME; Miners, JO; Robson, RA; Smith, KJ; Veronese, ME, 1988
)
3.16
"Tolbutamide has been used as a model drug for an examination of the effects of eleven substituted imidazole compounds on hepatic metabolism in vivo. "( Inhibition of tolbutamide metabolism by substituted imidazole drugs in vivo: evidence for a structure-activity relationship.
Back, DJ; Tjia, JF, 1985
)
2.07

Actions

Tolbutamide elicits an increase in [Ca2+li in beta- and delta-cells, regardless of glucose concentrations. Tolbutamide increase in serum was not associated with a rise of IRI level in serum.

ExcerptReferenceRelevance
"Tolbutamide continued to activate the enzyme in cells in which insulin receptor had been destroyed by trypsin-pretreatment."( Effects of sulfonylureas on membrane-bound low Km cyclic AMP phosphodiesterase in rat fat cells.
Kanatsuka, A; Kumagai, A; Makino, H; Osegawa, M, 1982
)
0.99
"Tolbutamide elicits an increase in [Ca2+li in beta- and delta-cells, regardless of glucose concentrations."( Different effects of tolbutamide and diazoxide in alpha, beta-, and delta-cells within intact islets of Langerhans.
Nadal, A; Quesada, I; Soria, B, 1999
)
1.34
"Tolbutamide increase in serum was not associated with a rise of IRI level in serum."( Interaction of tolbutamide and chloramphenicol in diabetic patients.
Brunová, E; Dvorácek, K; Grafnetterová, J; Pavlik, F; Platilová, H; Slabochová, Z, 1977
)
1.33
"Even tolbutamide could not increase the biosynthesis of insulin in this condition."( Effects of thiamine deficiency on the biosynthesis of insulin in rats.
Rathanaswami, P; Sundaresan, R, 1991
)
0.74
"The tolbutamide-induced increase in sodium was reversed to a decrease when Ca2+ was omitted from the incubation medium."( Sulphonamide modulation of sodium content in rat pancreatic islets.
Ali, L; Hellman, B; Wesslén, N, 1988
)
0.76

Treatment

Tolbutamide was associated with a decreased survival rate of 50% (n = 12) and an increase in the incidence and duration of reperfusion-induced arrhythmias. The tolbutamide treated group showed a mean blood glucose level which was only 33.8% lower than that of the control group. Tolbutamide did not markedly affect the slope of the terminal portion of the plasma concentration.

ExcerptReferenceRelevance
"Tolbutamide treatment markedly depressed the IRI response to glucose (P less than 0.005) or arginine (P less than 0.0005) infusion and the IRG response to arginine (P less than 0.01)."( Suppressive effect of long term sulfonylurea treatment on A, B, and D cells of normal rat pancreas.
Brunetti, P; Filipponi, P; Marcelli, M; Nicoletti, I; Pacifici, R; Santeusanio, F, 1983
)
0.99
"Tolbutamide pretreatment was associated with a decreased survival rate of 50% (n = 12) and an increase in the incidence and duration of reperfusion-induced arrhythmias."( Effects of nicorandil administration on survival rate and arrhythmias during reperfusion in anesthetized rabbits.
Das, B; Karanth, KS; Sarkar, C, 2001
)
1.03
"The tolbutamide treated group showed a mean blood glucose level which was only 33.8% lower than that of the control group."( An aqueous extract of the green leafy vegetable Ipomoea aquatica is as effective as the oral hypoglycaemic drug tolbutamide in reducing the blood sugar levels of Wistar rats.
Jansz, ER; Malalavidhane, S; Wickramasinghe, SM, 2001
)
1
"Tolbutamide treatment did not markedly affect the slope of the terminal portion of the plasma concentration vs."( Pharmacokinetic analysis of the interaction between dicoumarol and tolbutamide in man.
Gilfrich, HJ; Groth, U; Jähnchen, E; Meinertz, T, 1976
)
1.21
"Tolbutamide-treated serum was then supplemented with glucose to control for potential effects of hypoglycemia."( Teratogenic effects of tolbutamide on early-somite mouse embryos in vitro.
Smoak, IW, 1992
)
1.32
"Tolbutamide treatment resulted in graded granule depletion which was maximal at 72 hr relative to control animals."( Quantitative morphometric studies of pancreatic islets obtained from tolbutamide-treated rats.
Kalkhoff, RK; Yorde, DE, 1986
)
1.23
"pretreatment with tolbutamide, glyburide or glipizide attenuated the KA-induced neuronal cell death in CA3 region of the hippocampus and hyperglycemia."( Effect of tolbutamide, glyburide and glipizide administered supraspinally on CA3 hippocampal neuronal cell death and hyperglycemia induced by kainic acid in mice.
Jung, JS; Kim, CH; Kim, SJ; Kim, SS; Lim, SM; Park, SH; Sim, YB; Suh, HW, 2014
)
1.13
"4 Treatment with tolbutamide in maturity-onset diabetics need not be modified if concurrent administration of naproxen is contemplated."( Effect of naproxen on glucose metabolism and tolbutamide kinetics and dynamics in maturity onset diabetics.
Lorenzi, M; Robins, DS; Varady, JC; Whiting, B; Williams, RL, 1981
)
0.85

Toxicity

ExcerptReferenceRelevance
" Glyburide has a therapeutic effectiveness comparable to that of the first-generation sulfonylurea chlorpropamide; however, it has a lower frequency of adverse effects."( Glyburide: a second-generation sulfonylurea hypoglycemic agent. History, chemistry, metabolism, pharmacokinetics, clinical use and adverse effects.
Feldman, JM,
)
0.13
" Thus, the question arose whether K(ATP) channel-blocking insulin secretagogues are beta-cell toxic as has already been suggested for sulfonylureas."( Beta-cell toxicity of ATP-sensitive K+ channel-blocking insulin secretagogues.
Jörns, A; Krautheim, A; Rustenbeck, I; Steinfelder, HJ, 2004
)
0.32
" An understanding of structure-activity relationships (SARs) of chemicals can make a significant contribution to the identification of potential toxic effects early in the drug development process and aid in avoiding such problems."( Developing structure-activity relationships for the prediction of hepatotoxicity.
Fisk, L; Greene, N; Naven, RT; Note, RR; Patel, ML; Pelletier, DJ, 2010
)
0.36
"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

Pharmacokinetics

The pharmacokinetic changes of tolbutamide were studied after oral administration to normal rabbits and mild and medium folate-induced renal failure rabbits. The average elimination half-life of hexobarbital had decreased from 624 to 262 min and that of to lbutamide from 292 to 160 min following rifampicin treatment.

ExcerptReferenceRelevance
" However, the subjects differed with respect to the elimination kinetics of dicoumarol and the effect of tolbutamide on some of the measured pharmacokinetic paramaters."( Pharmacokinetic analysis of the interaction between dicoumarol and tolbutamide in man.
Gilfrich, HJ; Groth, U; Jähnchen, E; Meinertz, T, 1976
)
0.71
"A pharmacokinetic model that incorporates linear binding of drug to plasma proteins and tissue indicates the same relationship between apparent volume of distribution and drug binding as that proposed by Gillette (1971) based on a simple distribution model."( Apparent volumes of distribution and drug binding to plasma proteins and tissues.
Gibaldi, M; McNamara, PJ, 1978
)
0.26
" The average elimination half-life of hexobarbital had decreased from 624 to 262 min and that of tolbutamide from 292 to 160 min following rifampicin treatment."( Stimulation of drug metabolism by rifampicin in patients with cirrhosis or cholestasis measured by increased hexobarbital and tolbutamide clearance.
Breimer, DD; Richter, E; Zilly, W, 1977
)
0.68
" The average elimination half-life of hexobarbital had decreased from 325 to 122 min and of tolbutamide from 418 to 183 min following rifampicin treatment."( Induction of drug metabolism in man after rifampicin treatment measured by increased hexobarbital and tolbutamide clearance.
Breimer, DD; Richter, E; Zilly, W, 1975
)
0.69
" The changes observed in the pharmacokinetic parameters of SMZ after tolbutamide treatment is due to the induction of liver N-acetyltransferase activity."( Effect of tolbutamide treatment on the pharmacokinetics of intravenously administered sulphamethoxazole in rabbits.
Garg, SK; Ghosh, SS; Mathur, VS, 1987
)
0.91
"Various pharmacokinetic parameters--disposition half-life, t1/2,z, metabolic clearance CLm, volume of distribution V, intrinsic clearance of unbound drug CLuint, and unbound volume of distribution of tissues (distributive tissue volume/fraction of drug in tissue unbound, VT/fuT--are compared in rat and human for nine weakly acidic drugs, phenytoin, hexobarbital, pentobarbital, phenylbutazone, warfarin, tolbutamide, valproate, phenobarbital, and amobarbital, and six weakly basic drugs, quinidine, chlorpromazine, propranolol, pentazocin, antipyrine, and diazepam."( Prediction of the disposition of nine weakly acidic and six weakly basic drugs in humans from pharmacokinetic parameters in rats.
Hanano, M; Iga, T; Sawada, Y; Sugiyama, Y, 1985
)
0.44
"A blood flow rate-limited pharmacokinetic model was developed to study the effect of sulfonamide on the plasma elimination and tissue distribution of 14C-tolbutamide (TB) in rats."( Physiologically based pharmacokinetics of drug-drug interaction: a study of tolbutamide-sulfonamide interaction in rats.
Hanano, M; Iga, T; Sawada, Y; Sugita, O; Sugiyama, Y, 1982
)
0.69
" Mean pharmacokinetic parameters (system plasma clearance, terminal phase rate constant, apparent volume of distribution at steady state) of tolbutamide were derived from individual tolbutamide plasma concentration-time curves generated after infusion."( Tenidap sodium does not alter the clearance or plasma protein binding of tolbutamide in healthy male volunteers.
Gardner, MJ; Wilner, KD, 1995
)
0.72
"There was no significant difference in the pharmacokinetic parameters of tolbutamide (500 mg) determined before and after 14 days treatment with tenoxicam (20 mg/day) in 7 healthy volunteers (6 male, 1 female)."( The effect of tenoxicam on tolbutamide pharmacokinetics and glucose concentrations in healthy volunteers.
Day, RO; Geisslinger, G; Paull, P; Williams, KM, 1995
)
0.82
" The result of the pharmacokinetic analysis showed no change in the elimination rate constant, but a significant increase in the volume of distribution in the OJ state."( Pharmacokinetics of tolbutamide following intravenous and oral administrations in rats with obstructive jaundice.
Furuhama, K; Kimura, T; Kurosaki, Y; Nakagami, H; Nakayama, T; Onodera, T; Yamao, T, 1994
)
0.61
"The pharmacodynamic properties of meloxicam, a new nonsteroidal antiinflammatory drug (NSAID), that go beyond those typical of an NSAID were examined."( General pharmacology of meloxicam--Part II: Effects on blood pressure, blood flow, heart rate, ECG, respiratory minute volume and interactions with paracetamol, pirenzepine, chlorthalidone, phenprocoumon and tolbutamide.
Engelhardt, G; Homma, D; Schlegel, K; Schnitzler, C; Utzmann, R, 1996
)
0.48
" There was no significant change in area under the curve or in the elimination half-life of tolbutamide."( Effects of Sho-saiko-to on the pharmacokinetics and pharmacodynamics of tolbutamide in rats.
Hirano, H; Iwamoto, K; Naora, K; Nishimura, N, 1998
)
0.75
" Noncompartmental pharmacokinetic parameters were calculated using standard equations and compared with those previously reported in Caucasian subjects using the Mann-Whitney U test."( Pharmacokinetics of tolbutamide in ethnic Chinese.
Bridge, S; Gross, AS; Shenfield, GM, 1999
)
0.63
" Thus, not only drug monitoring but also pharmacokinetic investigations from blood plasma have become possible without further sample pretreatment."( Pharmacokinetic investigations with direct injection of plasma samples: possible savings using capillary electrophoresis (CE).
Kunkel, A; Wätzig, H, 1999
)
0.3
" There was approximately 10% increase in AUC0-24 and Cmax for tolbutamide in the presence of diltiazem."( Pharmacokinetic interaction between diltiazem and tolbutamide.
Dixit, AA; Rao, YM, 1999
)
0.8
" It had little effect, however, on the pharmacokinetic parameters of diazepam after intravenous administration at 10 mg kg(-1)."( Interaction of drugs and Chinese herbs: pharmacokinetic changes of tolbutamide and diazepam caused by extract of Angelica dahurica.
Ishihara, K; Kamei, H; Kitada, M; Kushida, H; Ohmori, S; Wakui, Y; Yanagisawa, T; Yuzurihara, M, 2000
)
0.54
"Liver slice experiments were performed to determine the slice intrinsic clearance and to extrapolate this to the in vivo liver intrinsic clearance in a physiologically based pharmacokinetic (PBPK)-like approach."( Utility of rat liver slices to estimate hepatic clearance for application in physiologically based pharmacokinetic modeling: a study with tolbutamide, a compound with low extraction efficiency.
Dormans, J; Haenen, B; Hamzink, M; Rompelberg, C; van Eijkeren, J; van Twillert, K, 2002
)
0.52
"The pharmacokinetic of tolbutamide was studied after the oral administration to normal rabbits or rabbits with mild to medium folate-induced renal failure."( Pharmacokinetics of tolbutamide after oral administration to rabbits with folate-induced renal failure.
Choi, JS; Shin, SC, 2003
)
0.95
"The primary objectives of the present study were to establish whether there was a pharmacokinetic or pharmacodynamic interaction between the probe drugs caffeine (CYP1A2), tolbutamide (CYP2C9), debrisoquine (CYP2D6), chlorzoxazone (CYP2E1) and midazolam (CYP3A4), when administered in combination as a cocktail."( Pharmacokinetic and pharmacodynamic assessment of a five-probe metabolic cocktail for CYPs 1A2, 3A4, 2C9, 2D6 and 2E1.
Aherne, Z; Blakey, GE; Lockton, JA; Norwood, P; Perrett, J; Plume, J; Russell, M, 2004
)
0.52
" Blood pressure and blood glucose measurements were used to assess pharmacodynamic interactions."( Pharmacokinetic and pharmacodynamic assessment of a five-probe metabolic cocktail for CYPs 1A2, 3A4, 2C9, 2D6 and 2E1.
Aherne, Z; Blakey, GE; Lockton, JA; Norwood, P; Perrett, J; Plume, J; Russell, M, 2004
)
0.32
"The five probe drugs when coadministered, in this dosing regimen, demonstrated no evidence of either a metabolic or pharmacodynamic interaction that might confound the conclusions drawn during a cocktail study."( Pharmacokinetic and pharmacodynamic assessment of a five-probe metabolic cocktail for CYPs 1A2, 3A4, 2C9, 2D6 and 2E1.
Aherne, Z; Blakey, GE; Lockton, JA; Norwood, P; Perrett, J; Plume, J; Russell, M, 2004
)
0.32
"The pharmacokinetic changes of tolbutamide were studied after oral administration to normal rabbits and mild and medium folate-induced renal failure rabbits."( Pharmacokinetics of tolbutamide after oral administration in rabbits with folate-induced renal failure.
Bae, HY; Choi, DH; Choi, JS, 2002
)
0.92
" The in vitro clearance value was incorporated in a physiologically based pharmacokinetic literature model of tolbutamide that accurately describes the plasma concentration."( Modeling the in vitro intrinsic clearance of the slowly metabolized compound tolbutamide determined in sandwich-cultured rat hepatocytes.
Barendregt, A; Blaauboer, BJ; Freidig, AP; Treijtel, N; van Eijkeren, JC, 2004
)
0.76
" Pharmacokinetic outcome showed that the individuals with CYP2C9 *1/*3 or CYP2C9 *3/*3 had slower metabolic elimination of tolbutamide than those with CYP2C9 *1/*1."( [Influence of cytochrom P450 CYP2C9 polymorphism on the pharmacokinetics of tolbutamide metabolism using oligonucleotide genotyping microarray].
Chen, K; Fang, Y; Li, J; Pei, F; Wang, R; Wang, SQ; Wen, SY, 2005
)
0.77
" The elimination half-life of tolbutamide was not altered by pomegranate juice administration."( Effects of pomegranate juice on human cytochrome P450 2C9 and tolbutamide pharmacokinetics in rats.
Arimori, K; Hidaka, M; Kawano, Y; Nagata, M; Okumura, M; Sekiya, H; Yamasaki, K, 2007
)
0.87
" 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
" In drug discovery single-dose pharmacokinetic studies in rats, each animal is generally used only once and then euthanized."( Proposed new addition to 3Rs for ethical and humane use of rats in pharmacokinetic studies--'Recycle'.
Balani, SK; Berg, C; Cardoza, K; Lee, FW; Lu, C; Zhang, J, 2008
)
0.35
" This study illustrated that the herb-drug interaction potential should be monitored by both in vitro and in vivo biotransformation/ pharmacokinetic parameters."( Pharmacokinetic interaction studies of tanshinones with tolbutamide, a model CYP2C11 probe substrate, using liver microsomes, primary hepatocytes and in vivo in the rat.
Lee, WY; Or, PM; Wang, X; Yeung, JH, 2010
)
0.61
"In the first DDI study, coadministration of ketoconazole (a CYP3A4 inhibitor) and clobazam increased clobazam's area under the concentration time curve from time zero extrapolated to infinity (AUC(0-∞) ) 54% and decreased clobazam's maximum plasma concentration (C(max) ) by 15% versus administration of clobazam alone, but the combination affected these pharmacokinetic parameters for N-CLB to a lesser degree."( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes.
Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012
)
0.38
"We conducted a pharmacokinetic (PK) study and a pharmacodynamic (PD) study to assess whether Roux-en-Y gastric bypass (RYGB) surgery is associated with significant changes to PK and PD of oral medications."( Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients.
Chalasani, N; Hall, SD; Jones, DR; Mattar, S; Tandra, S; Vuppalanchi, R, 2013
)
0.39
" Compared with controls, the RYGB group had brisk natriuresis, with significantly lower tmax for urine sodium (1."( Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients.
Chalasani, N; Hall, SD; Jones, DR; Mattar, S; Tandra, S; Vuppalanchi, R, 2013
)
0.39
"RYGB recipients have significantly shorter tmax for the studied orally administered medications, but otherwise no other significant changes in PK were reported."( Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients.
Chalasani, N; Hall, SD; Jones, DR; Mattar, S; Tandra, S; Vuppalanchi, R, 2013
)
0.39
" Plasma concentrations of tolbutamide, 4-hydroxytolbutamide, ticagrelor, and AR-C124910XX were determined for pharmacokinetic analyses."( Evaluation of the pharmacokinetic interaction between ticagrelor and tolbutamide, a cytochrome P450 2C9 substrate, in healthy volunteers.
Butler, K; Mitchell, P; Teng, R, 2013
)
0.92
"Ticagrelor had no effect on tolbutamide or 4-hydroxytolbutamide pharmacokinetic parameters."( Evaluation of the pharmacokinetic interaction between ticagrelor and tolbutamide, a cytochrome P450 2C9 substrate, in healthy volunteers.
Butler, K; Mitchell, P; Teng, R, 2013
)
0.92
"Microdose study enables us to understand the pharmacokinetic profiles of drugs in humans prior to the conventional clinical trials."( Microdose pharmacogenetic study of ¹⁴C-tolbutamide in healthy subjects with accelerator mass spectrometry to examine the effects of CYP2C9∗3 on its pharmacokinetics and metabolism.
Aoyama, S; Hamabe, Y; Hasegawa, S; Ikeda, T; Kainuma, M; Maeda, K; Matsui, T; Nozawa, K; Sugiyama, Y; Tozuka, Z, 2013
)
0.66
" In vitro half-life for disappearance of each compound was converted to hepatic clearance using the well stirred model, with and without correction for plasma protein binding."( Meeting the challenge of predicting hepatic clearance of compounds slowly metabolized by cytochrome P450 using a novel hepatocyte model, HepatoPac.
Chan, TS; Kehtani, SR; Khetani, SR; Moore, A; Tweedie, D; Yu, H, 2013
)
0.39
"The aim of this study was to present a deductive compartment pharmacokinetic (PK) model to predict the concentration profiles of drugs in plasma and peritoneal fluid in peritoneal dialysis (PD) rats."( Effects of peritoneal dialysis on pharmacotherapy: a deductive pharmacokinetic-model approach to predict drug concentration profiles in plasma and peritoneal fluid.
Aiba, T; Horiuchi, M; Kurosaki, Y; Moriyama, S; Takahata, Y, 2014
)
0.4
" Similar pharmacokinetic changes were observed in HL rats after oral administration of tolbutamide."( Pharmacokinetics of tolbutamide and its metabolite 4-hydroxy tolbutamide in poloxamer 407-induced hyperlipidemic rats.
Cho, YY; Choi, HD; Choi, MR; Kang, HE; Kim, YC; Kwon, MH, 2014
)
0.95
" The purpose of the study was to investigate the pharmacokinetic of four probe drugs in adriamycin (ADR)-induced nephropathy rat."( Pharmacokinetic of four probe drugs in adriamycin-induced nephropathy rat.
Chen, WH; Chen, ZB; Hu, LF; Li, D; Lin, FY; Yu, XG; Zhi, AY, 2014
)
0.4
" The analytical method was applied to support a pharmacokinetic study of simultaneous estimation of lenalidomide, ibrutinib, and its active metabolite PCI-45227 in Wistar rat."( Simultaneous quantification of lenalidomide, ibrutinib and its active metabolite PCI-45227 in rat plasma by LC-MS/MS: application to a pharmacokinetic study.
Govindarajulu, B; Rangasamy, M; Thappali, S; Vakkalanka, S; Veeraraghavan, S; Viswanadha, S, 2015
)
0.42
"A suitable liquid chromatography tandem mass spectrometry (LC-MS/MS) method is required to determine pelubiprofen and its active metabolite, trans-alcohol (M-D), in human plasma for pharmacokinetic studies of pelubiprofen preparations."( Development and validation of an LC-MS/MS method for the determination of pelubiprofen and its active metabolite, trans-alcohol, in human plasma and its application to pharmacokinetic study.
Hong, J; Jo, MH; Kim, BH; Kim, JI; Lee, KT; Park, JS; Ryu, JH; Shim, WS; Yim, SV, 2015
)
0.42
" The aim of the present study was to evaluate in vivo pharmacokinetic (PK) interaction between allopathic drugs tolbutamide (TOLBU), amlodipine (AMLO), and phenacetin (PHENA) at low (L) and high (H) doses with ethanolic extract (EL) from GS."( In vivo pharmacokinetic interaction by ethanolic extract of Gymnema sylvestre with CYP2C9 (Tolbutamide), CYP3A4 (Amlodipine) and CYP1A2 (Phenacetin) in rats.
Kharkar, P; Pandita, N; Sahu, N; Vaghela, M, 2017
)
0.89
" Previously published physiologically based pharmacokinetic (PBPK) models of tolbutamide are based on an assumption that its metabolic clearance is exclusively through CYP2C9; however, many studies indicate that CYP2C9 metabolism is only responsible for 80-90% of the total clearance."( Physiologically Based Pharmacokinetic Modelling of Cytochrome P450 2C9-Related Tolbutamide Drug Interactions with Sulfaphenazole and Tasisulam.
Chappell, J; Kellie Turner, P; Ng, WT; Perkins, EJ; Posada, M; Twelves, C, 2018
)
0.94
" There were no significant differences in the pharmacokinetic parameters of caffeine, omeprazole, metoprolol, chlorzoxazone, and midazolam between the SGI-pretreated and control groups."( Influence of Shenxiong Glucose Injection on the Activities of Six CYP Isozymes and Metabolism of Warfarin in Rats Assessed Using Probe Cocktail and Pharmacokinetic Approaches.
Gong, Z; Huang, J; Li, Y; Liu, C; Liu, T; Lu, Y; Pan, J; Sun, J; Wang, Y; Zheng, J; Zheng, L, 2017
)
0.46
"To investigate the pharmacokinetic (PK) and pharmacodynamic (PD) mechanism of the herb-drug interactions (HDIs) between GAD and BBR."( Beneficial herb-drug interaction of Gnaphalium affine extract on benzbromarone: A pharmacokinetic and pharmacodynamic study in rats.
Fan, S; Han, S; Liu, X; Yang, Q, 2022
)
0.72
" 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

Compound-Compound Interactions

Biotransformation rates of bupropion administered either separately or in combined with tolbutamide were compared. In the present study, in vitro enzyme kinetic data were used to predict the in vivo clearance and drug-drug interaction potential of four well known CYP2C9 substrates.

ExcerptReferenceRelevance
" From these findings, it is suggested that physiologically based pharmacokinetic analysis could be generally useful to predict approximate plasma and tissue concentrations of a drug in the presence of drug-drug interaction."( Physiologically based pharmacokinetics of drug-drug interaction: a study of tolbutamide-sulfonamide interaction in rats.
Hanano, M; Iga, T; Sawada, Y; Sugita, O; Sugiyama, Y, 1982
)
0.49
"To assess the degree to which the maximum unbound concentration of inhibitor at the inlet to the liver (I(inlet,u,max), used in the prediction of drug-drug interactions, overestimates the unbound concentration in the liver."( Quantitative prediction of in vivo drug-drug interactions from in vitro data based on physiological pharmacokinetics: use of maximum unbound concentration of inhibitor at the inlet to the liver.
Ito, K; Kanamitsu, S; Sugiyama, Y, 2000
)
0.31
" In the present study, in vitro enzyme kinetic data were used to predict the in vivo clearance and drug-drug interaction potential of four well known CYP2C9 substrates (tolbutamide, fluvastatin, ibuprofen and diclofenac) that are frequently used as benchmark substances in screening programs."( An evaluation of the in vitro metabolism data for predicting the clearance and drug-drug interaction potential of CYP2C9 substrates.
Andersson, TB; Bredberg, E; Ericsson, H; Sjöberg, H, 2004
)
0.52
" The method is simple, rapid and rugged, and has been applied successfully to sample analysis in support of a drug-drug interaction study."( Simultaneous determination of tolbutamide, omeprazole, midazolam and dextromethorphan in human plasma by LC-MS/MS--a high throughput approach to evaluate drug-drug interactions.
Bertelsen, K; Guo, P; Han, F; Huang, MQ; Lin, ZJ; Weng, N; Zhang, W; Zhao, H, 2010
)
0.65
"Abstract: The activities of four CYP450 enzymes (CYP3A, 1A2, 2El and 2C) and the mRNA expression levels of CYP1A2, 2El, 2Cll and 3A1 in rat liver were determined after Wistar rats were orally administered with brucine (BR) at three dosage levels (3, 15 and 60 mg."( Effects of brucine combined with glycyrrhetinic acid or liquiritin on rat hepatic cytochrome P450 activities in vivo.
Chen, Y; Du, P; Han, FM; Wu, WH; Xing, PP, 2011
)
0.37
"To investigate potential drug-drug interactions between clobazam and cytochrome P450 (CYP) isoenzyme substrates, inhibitors, and inducers."( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes.
Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012
)
0.38
"Two, prospective, open-label, single-center, drug-drug interaction (DDI) studies and a population pharmacokinetics analysis of seven multicenter phase II-III trials."( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes.
Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012
)
0.38
"Fifty-four healthy adult volunteers were enrolled in the two drug-drug interaction studies; 53 completed the studies."( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes.
Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012
)
0.38
"In the first drug-drug interaction study, 36 participants received a single oral dose of clobazam 10 mg on day 1, followed by either ketoconazole 400 mg once/day or omeprazole 40 mg once/day on days 17-22, with a single dose of clobazam 10 mg coadministered on day 22, to study the effects of CYP3A4 or CYP2C19 inhibition, respectively, on clobazam and its active metabolite N-desmethylclobazam (N-CLB)."( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes.
Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012
)
0.38
" In the second DDI study, no clinically significant drug-drug interactions were observed between clobazam 40 mg and the CYP probe substrates caffeine or tolbutamide."( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes.
Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012
)
0.58
"These findings suggest no clinically meaningful drug-drug interactions between clobazam and drugs metabolized by CYP3A4, CYP2C19, CYP1A2, or CYP2C9."( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes.
Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012
)
0.38
"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
" While grapefruit juice has been extensively studied with respect to its drug-drug interaction potential, numerous other fruit juices such as cranberry juice, orange juice, grape juice, pineapple juice and pomegranate juice have also been investigated for its potential to show drug-drug interaction of any clinical relevance."( Is pomegranate juice a potential perpetrator of clinical drug-drug interactions? Review of the in vitro, preclinical and clinical evidence.
Srinivas, NR, 2013
)
0.39
" The biotransformation rates of bupropion administered either separately or in combined with tolbutamide were compared in this new study."( Assessment of CYP2B6 activity in rats: a cocktail study with bupropion alone and in combined with tolbutamide.
Du, X; Hu, L; Wang, Z; Xu, RA; Zhang, X; Zhu, H, 2013
)
0.83
" We aimed to compare mortality and cardiovascular risk among users of metformin in combination with pharmacologically different ISs."( Metformin in combination with various insulin secretagogues in type 2 diabetes and associated risk of cardiovascular morbidity and mortality--a retrospective nationwide study.
Andersson, C; Fosbøl, EL; Gislason, G; Køber, L; Mogensen, UM; Scheller, NM; Schramm, TK; Torp-Pedersen, C; Vaag, A, 2015
)
0.42
"Most ISs in combination with metformin were associated with similar mortality and cardiovascular risk."( Metformin in combination with various insulin secretagogues in type 2 diabetes and associated risk of cardiovascular morbidity and mortality--a retrospective nationwide study.
Andersson, C; Fosbøl, EL; Gislason, G; Køber, L; Mogensen, UM; Scheller, NM; Schramm, TK; Torp-Pedersen, C; Vaag, A, 2015
)
0.42
"Botanical medicines are frequently used in combination with therapeutic drugs, imposing a risk for harmful botanical-drug interactions (BDIs)."( An ex vivo approach to botanical-drug interactions: a proof of concept study.
Gurley, BJ; Markowitz, JS; Munoz, J; Wang, X; Zhu, HJ, 2015
)
0.42
" CETP inhibitors are likely to be utilized as 'add-on' therapy to statins in patients receiving concomitant medications, so the potential for evacetrapib to cause clinically important drug-drug interactions (DDIs) with cytochromes P450 (CYP) was evaluated."( CYP-mediated drug-drug interactions with evacetrapib, an investigational CETP inhibitor: in vitro prediction and clinical outcome.
Cannady, EA; Friedrich, S; Krueger, KA; Nicholls, SJ; Rehmel, JR; Suico, JG; Wang, MD, 2015
)
0.42
"The competition of two drugs for the same metabolizing enzyme is a common mechanism for drug-drug interactions that can lead to altered kinetics in drug metabolism and altered elimination rates in vivo."( Measuring Drug Metabolism Kinetics and Drug-Drug Interactions Using Self-Assembled Monolayers for Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry.
Anderson, LL; Berns, EJ; Bugga, P; George, AL; Mrksich, M, 2016
)
0.43
" Therefore, these models are not useful for predicting the magnitude of CYP2C9 drug-drug interactions (DDIs)."( Physiologically Based Pharmacokinetic Modelling of Cytochrome P450 2C9-Related Tolbutamide Drug Interactions with Sulfaphenazole and Tasisulam.
Chappell, J; Kellie Turner, P; Ng, WT; Perkins, EJ; Posada, M; Twelves, C, 2018
)
0.71
" Since drug-drug interactions can cause serious adverse effects and impede overall curative effects, evidence regarding the risk associated with drug-drug interactions between Hb-V and such simultaneously administered drugs is needed."( Assessing cytochrome P450-based drug-drug interactions with hemoglobin-vesicles, an artificial red blood cell preparation, in healthy rats.
Ohtsuki, S; Otagiri, M; Sakai, H; Taguchi, K; Tokuno, M; Yamasaki, K, 2020
)
0.56
" Understanding potential drug-drug interactions (DDIs) informs proper dosing when co-administering tucatinib with other therapies."( Evaluation of Safety and Clinically Relevant Drug-Drug Interactions with Tucatinib in Healthy Volunteers.
Abdulrasool, LI; Endres, CJ; Lee, A; Mayor, JG; Rustia, EL; Sun, H; Topletz-Erickson, A; Walker, L, 2022
)
0.72
"In this study, the drug-drug interaction potential of vatiquinone with cytochrome P450 (CYP) substrates was investigated in both in vitro and clinical studies."( Evaluation of vatiquinone drug-drug interaction potential in vitro and in a phase 1 clinical study with tolbutamide, a CYP2C9 substrate, and omeprazole, a CYP2C19 substrate, in healthy subjects.
Barrett, R; Lee, L; Ma, J; Murase, K; Thoolen, M, 2022
)
0.94
" In an open-label, drug-drug interaction study in 18 healthy human subjects, a single oral dose of 500 mg tolbutamide and 40 mg omeprazole was administered on day 1, followed by a washout of 7 days."( Evaluation of vatiquinone drug-drug interaction potential in vitro and in a phase 1 clinical study with tolbutamide, a CYP2C9 substrate, and omeprazole, a CYP2C19 substrate, in healthy subjects.
Barrett, R; Lee, L; Ma, J; Murase, K; Thoolen, M, 2022
)
1.15

Bioavailability

Pomegranate juice inhibited human CYP2C9 activity and increased tolbutamide bioavailability in rats. Sho-saiko-to may potentiate the hypoglycemic effects of tol butamide in the early period after oral administration.

ExcerptReferenceRelevance
" There was no consistent effect on the metabolism of dicumarol following treatment with amitriptyline or nortriptyline although the bioavailability of dicumarol appeared to be increased."( Effects of tricyclic antidepressants on drug metabolism.
Birkett, DJ; Graham, GG; Pond, SM; Wade, DN, 1975
)
0.25
" Two independent studies have shown that aspirin markedly reduces the bioavailability of diclofenac, as measured by "area under the curve"."( Diclofenac sodium (Voltarol): drug interactions and special studies.
Fowler, PD, 1979
)
0.26
"The partial area method was investigated for evaluation of equivalency in the rate of absorption of immediate release formulations."( An alternative approach for assessment of rate of absorption in bioequivalence studies.
Chen, ML, 1992
)
0.28
" It is concluded that magnesium hydroxide increased the early bioavailability of tolbutamide, resulting in enhanced insulin and glucose responses."( Effect of magnesium hydroxide on the absorption and efficacy of tolbutamide and chlorpropamide.
Kivistö, KT; Neuvonen, PJ, 1992
)
0.75
" Fluoxetine is well absorbed after oral administration in both the fed and fasted states and demonstrates dose proportionality."( Fluoxetine: clinical pharmacology and physiologic disposition.
Aronoff, GR; Bergstrom, RF; Enas, GG; Farid, NA; Lemberger, L; Wolen, RL, 1985
)
0.27
"Relative bioavailability and pharmacodynamics of tolbutamide from two different commercially available tablet products have been evaluated in healthy subjects in a single-dose crossover study."( Effect of food and tablet age on relative bioavailability and pharmacodynamics of two tolbutamide products.
Albert, KS; Antal, EJ; Ayres, JW; Olson, SC, 1985
)
0.75
" Glyburide and glipizide are well absorbed after oral administration."( Glyburide and glipizide, second-generation oral sulfonylurea hypoglycemic agents.
Prendergast, BD,
)
0.13
" Food did not affect the bioavailability of any of the four drugs, but delayed Gz absorption."( Kinetics-effect relations of glipizide and other sulfonylureas.
Melander, A; Sartor, G; Scherstén, B; Wåhlin-Boll, E, 1980
)
0.26
" The bioavailability of glipizide was apparently greater than that of glibenclamide."( Comparative single-dose kinetics and effects of four sulfonylureas in healthy volunteers.
Melander, A; Sartor, G; Scherstén, B; Wåhlin-Boll, E, 1980
)
0.26
" Therefore, one possible mechanism accounting for the more rapid and short-lived hypoglycemic action of A-4166 in vivo, as compared with tolbutamide, may involve the reported differences in the bioavailability of A-4166."( Insulin secretion from isolated rat islets induced by the novel hypoglycemic agent A-4166, a derivative of D-phenylalanine.
Kikuchi, M; Niki, I; Oka, Y; Sakurada, M; Tsukuda, K, 1998
)
0.5
" Furthermore, it is considered that elevation of the gastrointestinal absorption rate by Sho-saiko-to might potentiate the hypoglycaemic effect of this sulphonylurea in the early period after oral administration."( Effects of Sho-saiko-to on the pharmacokinetics and pharmacodynamics of tolbutamide in rats.
Hirano, H; Iwamoto, K; Naora, K; Nishimura, N, 1998
)
0.53
" These dissolution characteristics of TB polymorphs were reflected in the oral absorption behavior in dogs; that is, the bioavailability increased in the order Form I < Form III < Form II approximately Form IV."( Characterization of tolbutamide polymorphs (Burger's forms II and IV) and polymorphic transition behavior.
Hirayama, F; Kimura, K; Uekama, K, 1999
)
0.63
" In the study of single oral administration of tolbutamide (50 mg/kg), co-administration of Sho-saiko-to tended to accelerate the initial absorption rate of tolbutamide."( A Chinese traditional medicine, sho-saiko-to (xiao-chaihu-tang), reduces the bioavailability of tolbutamide after oral administration in rats.
Hirano, H; Iwamoto, K; Naora, K; Nishimura, N, 1999
)
0.78
"The value of I(inlet,u,max) differed from the concentration in each compartment, depending on the intrinsic metabolic clearance in the liver, first-order absorption rate constant, non-hepatic clearance and liver-to-blood concentration ratio (Kp) of the inhibitor."( Quantitative prediction of in vivo drug-drug interactions from in vitro data based on physiological pharmacokinetics: use of maximum unbound concentration of inhibitor at the inlet to the liver.
Ito, K; Kanamitsu, S; Sugiyama, Y, 2000
)
0.31
"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 absorption rate of glibenclamide and tolbutamide was not affected by food."( [Timing of administration of sulfonyl urea derivatives].
de Smet, PA; Fischer, HR, 2000
)
0.57
"The purpose of the present study was to evaluate the enhancement of tolbutamide (TBM) oral bioavailability and hypoglycaemic activity through complexation with beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD)."( Oral bioavailability and hypoglycaemic activity of tolbutamide/cyclodextrin inclusion complexes.
Fernandes, C; Teixeira, F; Veiga, F, 2000
)
0.79
" There was approximately 20% increase in mean absorption rate constant and 26% increase in mean bioavailability of tolbutamide in the presence of clarithromycin."( Effect of clarithromycin on the pharmacokinetics of tolbutamide.
Dixit, AA; Jayasagar, G; Kishan, V; Rao, YM, 2000
)
0.77
" Furthermore, it is considered that the increase in the gastrointestinal absorption rate by Sho-saiko-to may potentiate the hypoglycemic effects of tolbutamide in the early period after oral administration."( [Effects of Chinese herbal medicines on intestinal drug absorption].
Nishimura, N, 2005
)
0.53
" Thus, we discovered that pomegranate juice inhibited human CYP2C9 activity and furthermore increased tolbutamide bioavailability in rats."( Effects of pomegranate juice on human cytochrome P450 2C9 and tolbutamide pharmacokinetics in rats.
Arimori, K; Hidaka, M; Kawano, Y; Nagata, M; Okumura, M; Sekiya, H; Yamasaki, K, 2007
)
0.8
" Human oral bioavailability is an important pharmacokinetic property, which is directly related to the amount of drug available in the systemic circulation to exert pharmacological and therapeutic effects."( Hologram QSAR model for the prediction of human oral bioavailability.
Andricopulo, AD; Moda, TL; Montanari, CA, 2007
)
0.34
"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
" However, maximum plasma concentration, half-life, area under the curve, and oral bioavailability were not different."( Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients.
Chalasani, N; Hall, SD; Jones, DR; Mattar, S; Tandra, S; Vuppalanchi, R, 2013
)
0.39
"This study aims to improve the drug oral bioavailability by co-administration with flavonoid inhibitors of the CYP2C isozyme and to establish qualitative and quantitative (QSAR) structure-activity relationships (SAR) between flavonoids and CYP2C."( Dietary flavonoids modulate CYP2C to improve drug oral bioavailability and their qualitative/quantitative structure-activity relationship.
Hsiong, CH; Hu, OY; Lee, MS; Pao, LH; Shih, TY; Wang, HJ, 2014
)
0.4
"Self-nanoemulsifying drug delivery system (SNEDDS) has immense potential in oral bioavailability enhancement of lipophilic drugs."( A Self-nanoemulsifying Drug Delivery System for Poorly Water Soluble Tolbutamide: Development, Optimization and Pharmacodynamic Studies.
Kumari, N; Lather, V; Pandita, D, 2017
)
0.69
"The present study demonstrates a successful development of SNEDDS formulation with an overall potential of bioavailability enhancement for tolbutamide, a BCS-II drug."( A Self-nanoemulsifying Drug Delivery System for Poorly Water Soluble Tolbutamide: Development, Optimization and Pharmacodynamic Studies.
Kumari, N; Lather, V; Pandita, D, 2017
)
0.89
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51
"Among the strategies for bioavailability improvement of poorly soluble drugs, co-amorphous systems have revealed to have a significant impact in the increase of the aqueous solubility of the drug, and at the same time increasing the amorphous state stability and dissolution rate when compared with the neat drug."( Structural, thermal, vibrational, solubility and DFT studies of a tolbutamide co-amorphous drug delivery system for treatment of diabetes.
de Sousa, FF; Lage, MR; Lima, ADDSG; Lopes, JA; R Sá, M; Ribeiro, PRS; Sarraguça, JMG; Sarraguça, MSC, 2022
)
0.96

Dosage Studied

No alteration of plasma half-life of warfarin, phenytoin, or tolbutamide was observed following dosage with the tricyclic antidepressants used. The effectiveness of tol butamide on [Ca(2+)](i) increase was reduced and the dose-response relations for insulin secretion induced by the agent was shifted toward the right in the UCP1-expressing cells.

ExcerptRelevanceReference
" No alteration of plasma half-life of warfarin, phenytoin, or tolbutamide was observed following dosage with the tricyclic antidepressants used."( Effects of tricyclic antidepressants on drug metabolism.
Birkett, DJ; Graham, GG; Pond, SM; Wade, DN, 1975
)
0.49
" In three dose-response experiments in which the perfusing glucose concentration was increased at 30-min intervals from an initial concentration of 25 mg/dl to a final concentration of 300 mg/dl, progressive increases in IRS release were noted at glucose concentrations of 100 mg/dl and above."( Release of immunoreactive somatostatin from the pancreas in response to glucose, amino acids, pancreozymin-cholecystokinin, and tolbutamide.
Arimura, A; Dobbs, RE; Harris, V; Ipp, E; Unger, RH; Vale, W, 1977
)
0.46
"A quantitative high-performance liquid chromatographic method for the determination of chlorpropamide, tolbutamide, and their respective hydrolysis products, p-chlorobenzenesulfonamide and p-toluenesulfonamide, in solid dosage forms was developed."( Stability-indicating high-performance liquid chromatographic determination of chlorpropamide, tolbutamide, and their respective sulfonamide degradates.
Butterfield, AG; Kolasinski, H; Lovering, EG; Matsui, FF; Robertson, DL, 1979
)
0.69
"This study was designed to focus on the genetic control of tolbutamide dispositon in humans and to provide insight into the potential for high accrued blood levels in individuals receiving fixed dosage regimens."( Pharmacogenetics of tolbutamide metabolism in humans.
Poffenbarger, PL; Scott, J, 1979
)
0.83
" The serum tolbutamide concentrations varied widely between the patients (from close to zero to 370 mumol/l (100 mug/ml)), yet the variation in dosage was only sixfold (0."( Serum tolbutamide and chlorpropamide concentrations in patients with diabetes mellitus.
Bitzén, PO; Melander, A; Sartor, G; Scherstén, B; Wåhlin, E, 1978
)
1.13
" Due to the high frequency of side effects it does not seem to be worthwhile to further investigate the therapeutic effect of MPC in a larger number of patients with different dosage regimens."( [Effect of methylpyrazole-carboxylic acid on carbohydrate and lipid metabolisms in patients with diabetes mellitus].
Hassalacher, Ch; Lang, PD; Vollmar, J; Wahl, P, 1975
)
0.25
" If this clearance does not change during hepatic disease, no dosage alterations for tolbutamide and other comparable drugs are necessary to maintain a constant concentration of unbound drug."( Influence of acute viral hepatitis on disposition and plasma binding of tolbutamide.
Blaschke, TF; Meffin, PJ; Melmon, KL; Rowland, M; Williams, RL, 1977
)
0.71
"An apparatus utilizing liquid turbulence to simulate hydrodynamic conditions generated by gastrointestinal peristalsis was designed to estimate drug release from solid oral dosage forms; This turbulence was achieved through special arrangements of a pipetting pump to a dissolution chamber."( A dissolution rate apparatus for the prediction of initial drug absorption patterns in beagles: tolbutamide tablets.
Joshi, NN; Lee, KS; Legore, AA; Picotte, P; Simmons, DL, 1975
)
0.47
" There was a significant dose-response relationship exists between TOL and IRI."( Dynamics of tolbutamide, glucose, and insulin interrelationships following varying doses of intravenous tolbutamide in normal subjects.
Ganda, OP; Gleason, RE; Kahn, CB; Soeldner, JS, 1975
)
0.63
" The dose-response curves for inhibition of I-KATP at different pHo's were found to coincide when plotted for the unionized concentrations of the drugs."( Effects of pH upon the inhibition by sulphonylurea drugs of ATP-sensitive K+ channels in cardiac muscle.
Findlay, I, 1992
)
0.28
" It also produced little or no changes in electroencephalogram (cat) and spinal reflex (cat) after intravenous dosing of 10 mg/kg."( Pharmacological studies with the alpha 2-adrenoceptor antagonist midaglizole. Part II: Central and peripheral nervous systems.
Hirohashi, M; Kasai, Y; Kojima, H; Takasuna, K; Usui, C, 1991
)
0.28
" The dosage was adjusted to obtain adequate control or up to the maximum recommended dosage."( Efficacy of gliclazide in comparison with other sulphonylureas in the treatment of NIDDM.
Harrower, AD, 1991
)
0.28
" After counting insulin-positive beta cells, dose-response curves were plotted and analyzed."( Tolbutamide stimulates proliferation of pancreatic beta cells in culture.
Moore, W; Popiela, H, 1991
)
1.72
" The inter-relationship of tolbutamide dosage and concentration, and glucose and insulin concentrations were therefore examined in 54 out-patients (the observational group) and in 20 patients studied under controlled conditions (the experimental group)."( The relationships between dose and concentration of tolbutamide and insulin and glucose responses in patients with non-insulin-dependent diabetes.
Alberti, KG; Antsiferov, ML; Ferner, RE; Kelman, AW; Rawlins, MD, 1991
)
0.83
" A graded dose-response relationship was found between PB treatment and most but not all parameters."( Drug metabolizing capacity in vitro and in vivo--II. Correlations between hepatic microsomal monooxygenase markers in phenobarbital-induced rats.
Houston, JB; Matthew, DE, 1990
)
0.28
" The magnitude of the hypoglycaemic effect was found to vary with the dosage administered and the storage time of the prepared extract."( A preliminary investigation of the possible hypoglycaemic activity of Asteracanthus longifolia.
Fernando, MR; Karunanayaka, EH; Thabrew, MI; Wickramasinghe, N, 1989
)
0.28
" Insulin secretory dose-response curves utilizing static incubations fit a single binding site model and established that glyburide (ED50 = 112 +/- 18 nM) is a more potent secretagogue than tolbutamide (ED50 = 15 +/- 3 microM)."( Increased cytosolic calcium. A signal for sulfonylurea-stimulated insulin release from beta cells.
Berg, M; Boyd, AE; Gaines, KL; Nelson, TY; Rajan, AS, 1987
)
0.46
" Since maintained contraction induced by oxytocin in a Ca-free solution could be repeated after making a relaxation dose-response curve to sulfonylurea, the most likely mechanism of sulfonylurea-induced uterine relaxation is not an increase in the efflux of Ca but an increase in the Ca-uptake by intracellular organelles."( Relaxant effects of sulfonylureas on induced contractions of rat uterine smooth muscle: role of intracellular calcium.
Anselmi, E; D'Ocon, MP; Villar, A, 1986
)
0.27
" On the other hand, the sulfonylurea (10(-4) M) shifted most points of the dose-response curve to the right for the contractile stimulation elicited by oxytocin, an influence not altered by the simultaneous presence of propranolol or sotalol."( Tolbutamide in vitro diminishes spontaneous and oxytocin-induced contractions of uterine smooth muscle from diestrous rats.
Gimeno, AL; Gimeno, MA; Goldraij, A; Sterin, AB, 1987
)
1.72
" The carbutamide dosage of 50 mg/kg per day prevented the infection in 90% of animals, whereas tolbutamide in the same dosage permitted infection in 100% of animals."( Effects of sulfonylurea compounds on Pneumocystis carinii.
Hughes, WT; Smith-McCain, BL, 1986
)
0.49
" In the first study, the effect of acute dosing (via an intravenous infusion of 5 mg h-1 for 3 h) on the glucose, insulin, hormonal, and intermediary metabolite responses to an intravenous glucose tolerance test was determined in six healthy male volunteers."( The effect of nicardipine on glucose and drug-stimulated insulin secretion in normal volunteers.
Baty, J; Dow, RJ; Isles, TE, 1985
)
0.27
" Dose-response analysis revealed a significant (p less than ."( Effect of tolbutamide and chlorpropamide on acetaldehyde metabolism in two inbred strains of mice.
Little, RG; Petersen, DR, 1985
)
0.67
" In the second experiment, tolbutamide and insulin were given to different groups of weanling lambs with the dosage increased every 2 weeks until signs of hypoglycemia began to appear."( Effect of insulin and tolbutamide on growth rate, blood glucose and body composition of lambs.
Cunningham, HM, 1968
)
0.86
" Only minimal adjustments of insulin dosage were required."( Successful use of oral diazoxide in the treatment of severe toxaemia of pregnancy.
Davis, D; Morgan, MY; Pohl, JE; Thurston, H, 1972
)
0.25
"The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of glyburide and glipizide, two second-generation oral sulfonylurea hypoglycemic agents, are reviewed."( Glyburide and glipizide, second-generation oral sulfonylurea hypoglycemic agents.
Prendergast, BD,
)
0.13
" A placebo dosage form was also administered to determine baseline glucose and insulin response to the meal."( The effect of food on the bioavailability and pharmacodynamics of tolbutamide in diabetic patients.
Albert, KS; Antal, EJ; Gillespie, WR; Phillips, JP, 1982
)
0.5
" For each of the four drugs, the steady state concentrations showed very large between-patient variations, not attributable to dosage or weight differences but to individual differences in drug kinetics and to insufficient compliance."( Kinetics-effect relations of glipizide and other sulfonylureas.
Melander, A; Sartor, G; Scherstén, B; Wåhlin-Boll, E, 1980
)
0.26
" The binding characteristics of these drugs were not altered when plasma containing either warfarin or tolbutamide at concentrations equivalent to those expected normally after therapeutic dosing were concomitantly spiked with therapeutic amounts of pirprofen."( Effect of pirprofen on protein binding of warfarin and tolbutamide in human plasma.
Chao, D; Luders, RC, 1981
)
0.72
" Dose-response curves were constructed before and during intra-arterial infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) (2 mg/min, n = 6) or vehicle (n = 6)."( Endothelial release of nitric oxide contributes to the vasodilator effect of adenosine in humans.
Banitt, P; Creager, MA; Lipson, DE; Rongen, GA; Smits, P; Williams, SB, 1995
)
0.29
" A dose-response relationship revealed that I5-HT was activated with an ED50 of 30 nM."( Whole-cell recordings of inwardly rectifying K+ currents activated by 5-HT1A receptors on dorsal raphe neurones of the adult rat.
Fox, AP; Kelly, JS; Penington, NJ, 1993
)
0.29
"The polymorphism phenomenon causes an important problem in the preparation of many pharmaceutical dosage forms, including oral suspensions, tablets, creams and suppositories."( Influence of the presence of trace amounts of metals on the polymorphism of tolbutamide.
Barba, C; del Castillo, B; Martin, MA; Olives, AI, 1996
)
0.52
" When membrane potential was plotted as a function of glucose concentration, the dose-response curve was shifted to the left."( Diminished fraction of blockable ATP-sensitive K+ channels in islets transplanted into diabetic mice.
Andreu, E; Martín, F; Montana, E; Nacher, V; Sanchez-Andrés, JV; Soria, B, 1996
)
0.29
" There was a small but statistically significant decrease (16%) in the clearance of tolbutamide in patients receiving the maximum recommended dosage of sertraline."( A study of the potential effect of sertraline on the pharmacokinetics and protein binding of tolbutamide.
Preskorn, SH; Tremaine, LM; Wilner, KD, 1997
)
0.74
" By applying the patch-clamp technique, dose-response curves for ATP and the sulfonylurea tolbutamide were obtained in inside-out patches."( RIN14B: a pancreatic delta-cell line that maintains functional ATP-dependent K+ channels and capability to secrete insulin under conditions where it no longer secretes somatostatin.
Berggren, PO; Bränström, R; Höög, A; Larsson, O; Wahl, MA, 1997
)
0.52
" Each subject underwent four frequently sampled intravenous glucose tolerance tests (FSIGTT), one with tolbutamide and three with the same insulin dosage (0."( Method of insulin administration has no effect on insulin sensitivity estimates from the insulin-modified minimal model protocol.
Bergman, RN; Boyadjian, R; Jinagouda, SD; Khan, A; Riad-Gabriel, M; Saad, MF; Sharma, A; Steil, GM, 1997
)
0.51
"5 after maternal dosing in mouse."( Tolbutamide: placental transfer, tissue distribution, and metabolic effects in murine embryos.
Emanuel, AN; Smoak, IW, 1998
)
1.74
" Consistent with the modulation of enzyme activity by genetic and other factors, wide interindividual variability occurs in the elimination and/or dosage requirements of prototypic CYP2C9 substrates."( Cytochrome P4502C9: an enzyme of major importance in human drug metabolism.
Birkett, DJ; Miners, JO, 1998
)
0.3
" The GER measured at 40 min after dosing was reduced to about 70% by the pretreatment of Sho-saiko-to (500 mg/kg)."( Effects of sho-saiko-to (xiao chai hu tang), a Chinese traditional medicine, on the gastric function and absorption of tolbutamide in rats.
Hirano, H; Iwamoto, K; Naora, K; Nishimura, N, 2001
)
0.52
" A single dosing of tolbutamide at levels of 25-200 mg/kg body weight decreased plasma glucose concentrations for 2 to 8 h after the dosing in chickens fed either diet."( Persistent hypoglycemia is induced by tolbutamide administration in broiler chickens fed a low-carbohydrate diet.
Akiba, Y; Ohtsu, H; Sato, K; Seki, Y, 2001
)
0.91
"The inhibition potential of drugs towards five major human hepatic cytochrome P450 (CYP) isozymes (CYP2A6, 3A4, 2C9, 2D6, and 2E1) was investigated via cassette dosing of the five probe substrates (coumarin, midazolam, tolbutamide, dextromethorphan, and chlorzoxazone) in human liver microsomes using a 96-well plate format."( High-throughput cytochrome P450 (CYP) inhibition screening via a cassette probe-dosing strategy. VI. Simultaneous evaluation of inhibition potential of drugs on human hepatic isozymes CYP2A6, 3A4, 2C9, 2D6 and 2E1.
Bu, HZ; Knuth, K; Magis, L; Teitelbaum, P, 2001
)
0.5
" Tolbutamide (CYP2C9), caffeine (CYP1A2), dextromethorphan (CYP2D6), oral midazolam (intestinal wall and hepatic CYP3A), and intravenous midazolam (hepatic CYP3A) were administered before, with short-term St John's wort dosing (900 mg), and after 2 weeks of intake (300 mg 3 times a day) to determine CYP activities."( The effects of St John's wort (Hypericum perforatum) on human cytochrome P450 activity.
Gorski, JC; Hall, SD; Hamman, MA; Huang, SM; Lesko, LJ; Wang, Z, 2001
)
1.22
" Moreover, the effectiveness of tolbutamide on [Ca(2+)](i) increase was reduced and the dose-response relations for insulin secretion induced by the agent was shifted toward the right in the UCP1-expressing cells."( Association of upregulated activity of K(ATP) channels with impaired insulin secretion in UCP1-expressing insulinoma cells.
Aso, K; Fukudome, M; Hashiguchi, H; Ishihara, H; Kakei, M; Koriyama, N; Nakazaki, M; Oka, Y; Tei, C; Yada, T, 2002
)
0.6
" A short 12-week study was conducted which incorporated a cross-over design and the results were examined by variance analysis after dosage was individualized to the patient's requirements."( CLINICAL STUDIES OF TOLAZAMIDE AND TOLBUTAMIDE: COMPARATIVE EFFECTIVENESS OF CONTROL OF DIABETES MELLITUS.
ANDERSON, DO; RENNIE, CS, 1963
)
0.52
" Therefore, these observations indicated that the dosage adjustment may be necessary for tolbutamide in patients with renal insufficiency."( Pharmacokinetics of tolbutamide after oral administration to rabbits with folate-induced renal failure.
Choi, JS; Shin, SC, 2003
)
0.86
" There was no difference in blood pressure and blood glucose concentrations following the cocktail and dosing of the individual probes."( Pharmacokinetic and pharmacodynamic assessment of a five-probe metabolic cocktail for CYPs 1A2, 3A4, 2C9, 2D6 and 2E1.
Aherne, Z; Blakey, GE; Lockton, JA; Norwood, P; Perrett, J; Plume, J; Russell, M, 2004
)
0.32
"The five probe drugs when coadministered, in this dosing regimen, demonstrated no evidence of either a metabolic or pharmacodynamic interaction that might confound the conclusions drawn during a cocktail study."( Pharmacokinetic and pharmacodynamic assessment of a five-probe metabolic cocktail for CYPs 1A2, 3A4, 2C9, 2D6 and 2E1.
Aherne, Z; Blakey, GE; Lockton, JA; Norwood, P; Perrett, J; Plume, J; Russell, M, 2004
)
0.32
" Because metabolism of some chemotherapeutic agents may involve CYP3A4, the potential inductive effect of the CINV dosing regimen of aprepitant on this metabolic pathway was evaluated using intravenous midazolam, a sensitive probe substrate of CYP3A4."( Evaluation of potential inductive effects of aprepitant on cytochrome P450 3A4 and 2C9 activity.
Blum, RA; Bradstreet, TE; Evans, JK; Gargano, C; Lee, Y; Majumdar, AK; Petty, KJ; Shadle, CR, 2004
)
0.32
" This result might be related to the accelerated in vivo absorption rate of tolbutamide by concomitant dosing with Sho-saiko-to in rats."( [Effects of Chinese herbal medicines on intestinal drug absorption].
Nishimura, N, 2005
)
0.56
" CYP2C9 probe (tolbutamide, 125 mg) and CYP3A4 probe (midazolam, 8 mg) were orally administered to 10 male healthy volunteers before and after GBE intake (360 mg/d) for 28 days, and they received 75 g glucose after the dosing of tolbutamide."( Effects of Ginkgo biloba extract on pharmacokinetics and pharmacodynamics of tolbutamide and midazolam in healthy volunteers.
Li, XD; Maruyama, S; Ohashi, K; Ohmori, Y; Oki, T; Uchida, S; Umegaki, K; Watanabe, H; Yamada, H; Yamada, S, 2006
)
0.92
" These results might suggest that CYP2D and 3A substrates should be prescribed for male and female cats using different dosage regimen."( Characterization of cytochrome P450-mediated drug metabolism in cats.
Regmi, NL; Sanda, S; Sasaki, K; Shah, SS; Shimoda, M, 2007
)
0.34
" INGAP-PP shifted to the left the dose-response curve of insulin secretion to increasing concentrations of glucose (EC(50) of 10."( INGAP-PP up-regulates the expression of genes and proteins related to K+ ATP channels and ameliorates Ca2+ handling in cultured adult rat islets.
Barbosa, HC; Borelli, MI; Boschero, AC; Bosqueiro, JR; Carneiro, EM; Del Zotto, H; Gagliardino, JJ; Rafacho, A; Silva, KE; Stoppiglia, LF, 2008
)
0.35
" In vivo assessment of CYP1A2 and CYP3A4 activities, perhaps by phenotyping approaches, could assist the optimization of CLZ dosage and minimize pharmacokinetic interactions with coadministered drugs."( Interindividual variation in relative CYP1A2/3A4 phenotype influences susceptibility of clozapine oxidation to cytochrome P450-specific inhibition in human hepatic microsomes.
D'Esposito, F; Edwards, RJ; Murray, M; Ramzan, I; Zhang, WV, 2008
)
0.35
" Thus, under conditions of excised patch recording, the dose-response relationship describing the inhibitory action of tolbutamide at human ß-cell or rat INS-1 cell K(ATP) channels was left-shifted in the presence of 2’-O-Me-cAMP, and this effect was abolished in INS-1 cells expressing a dominant-negative Epac2."( Facilitation of ß-cell K(ATP) channel sulfonylurea sensitivity by a cAMP analog selective for the cAMP-regulated guanine nucleotide exchange factor Epac.
Chepurny, OG; Dzhura, I; Genieser, HG; Holz, GG; Leech, CA; Schwede, F,
)
0.34
" 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
"Abstract: The activities of four CYP450 enzymes (CYP3A, 1A2, 2El and 2C) and the mRNA expression levels of CYP1A2, 2El, 2Cll and 3A1 in rat liver were determined after Wistar rats were orally administered with brucine (BR) at three dosage levels (3, 15 and 60 mg."( Effects of brucine combined with glycyrrhetinic acid or liquiritin on rat hepatic cytochrome P450 activities in vivo.
Chen, Y; Du, P; Han, FM; Wu, WH; Xing, PP, 2011
)
0.37
" Concomitant use of drugs metabolized by CYP2D6 may require dosage adjustment."( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes.
Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012
)
0.38
" Tolbutamide had no effect on the Cmax, area under the concentration curve over the 2-hour dosing interval (AUC0-τ), t1/2 or tmax of either ticagrelor or AR-C124910XX."( Evaluation of the pharmacokinetic interaction between ticagrelor and tolbutamide, a cytochrome P450 2C9 substrate, in healthy volunteers.
Butler, K; Mitchell, P; Teng, R, 2013
)
1.53
" 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
)
0.42
" Understanding potential drug-drug interactions (DDIs) informs proper dosing when co-administering tucatinib with other therapies."( Evaluation of Safety and Clinically Relevant Drug-Drug Interactions with Tucatinib in Healthy Volunteers.
Abdulrasool, LI; Endres, CJ; Lee, A; Mayor, JG; Rustia, EL; Sun, H; Topletz-Erickson, A; Walker, L, 2022
)
0.72
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (4)

RoleDescription
hypoglycemic agentA drug which lowers the blood glucose level.
potassium channel blockerAn agent that inhibits cell membrane glycoproteins that are selectively permeable to potassium ions.
human metaboliteAny mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
insulin secretagogueA secretagogue that causes the secretion of insulin.
[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]

Drug Classes (1)

ClassDescription
N-sulfonylureaA urea in which one of the hydrogens attached to a nitrogen of the urea group is replaced by a sulfonyl group. The N-sulfonylurea moiety is a key group in various herbicides, as well as in a number of antidiabetic drugs used in the management of type 2 diabetis mellitus.
[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]

Pathways (5)

PathwayProteinsCompounds
Metabolism14961108
Biological oxidations150276
Phase I - Functionalization of compounds69175
Cytochrome P450 - arranged by substrate type30110
Xenobiotics450

Protein Targets (40)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, MAJOR APURINIC/APYRIMIDINIC ENDONUCLEASEHomo sapiens (human)Potency0.01260.003245.467312,589.2998AID2517
Chain A, TYROSYL-DNA PHOSPHODIESTERASEHomo sapiens (human)Potency15.84890.004023.8416100.0000AID485290
acetylcholinesteraseHomo sapiens (human)Potency38.90180.002541.796015,848.9004AID1347398
SMAD family member 2Homo sapiens (human)Potency21.76270.173734.304761.8120AID1346859
SMAD family member 3Homo sapiens (human)Potency21.76270.173734.304761.8120AID1346859
GLI family zinc finger 3Homo sapiens (human)Potency10.59090.000714.592883.7951AID1259369
AR proteinHomo sapiens (human)Potency13.89230.000221.22318,912.5098AID743036; AID743053
aldehyde dehydrogenase 1 family, member A1Homo sapiens (human)Potency39.81070.011212.4002100.0000AID1030
thyroid stimulating hormone receptorHomo sapiens (human)Potency39.81070.001318.074339.8107AID926; AID938
glucocorticoid receptor [Homo sapiens]Homo sapiens (human)Potency25.11890.000214.376460.0339AID588532
retinoic acid nuclear receptor alpha variant 1Homo sapiens (human)Potency31.29370.003041.611522,387.1992AID1159552; AID1159555
retinoid X nuclear receptor alphaHomo sapiens (human)Potency52.39210.000817.505159.3239AID1159527; AID588546
pregnane X nuclear receptorHomo sapiens (human)Potency68.24100.005428.02631,258.9301AID1346982
GVesicular stomatitis virusPotency15.09160.01238.964839.8107AID1645842
peroxisome proliferator activated receptor gammaHomo sapiens (human)Potency33.48890.001019.414170.9645AID743191
gemininHomo sapiens (human)Potency1.41250.004611.374133.4983AID624297
muscleblind-like protein 1 isoform 1Homo sapiens (human)Potency63.09570.00419.962528.1838AID2675
muscarinic acetylcholine receptor M1Rattus norvegicus (Norway rat)Potency0.02820.00106.000935.4813AID943
lethal factor (plasmid)Bacillus anthracis str. A2012Potency3.98110.020010.786931.6228AID912
lamin isoform A-delta10Homo sapiens (human)Potency0.22390.891312.067628.1838AID1487
Interferon betaHomo sapiens (human)Potency14.98180.00339.158239.8107AID1347407; AID1645842
HLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)Potency15.09160.01238.964839.8107AID1645842
Inositol hexakisphosphate kinase 1Homo sapiens (human)Potency15.09160.01238.964839.8107AID1645842
cytochrome P450 2C9, partialHomo sapiens (human)Potency15.09160.01238.964839.8107AID1645842
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
ATP-binding cassette sub-family C member 3Homo sapiens (human)IC50 (µMol)133.00000.63154.45319.3000AID1473740
Multidrug resistance-associated protein 4Homo sapiens (human)IC50 (µMol)133.00000.20005.677410.0000AID1473741
Solute carrier family 22 member 6Rattus norvegicus (Norway rat)Ki55.50001.60005.744010.0000AID598879; AID679148
Bile salt export pumpRattus norvegicus (Norway rat)IC50 (µMol)1,000.00000.40002.75008.6000AID1209456
Bile salt export pumpHomo sapiens (human)IC50 (µMol)567.00000.11007.190310.0000AID1209455; AID1443980; AID1449628; AID1473738
Cytochrome P450 2C9 Homo sapiens (human)IC50 (µMol)0.39200.00002.800510.0000AID1862574; AID1884502
Cytochrome P450 2C9 Homo sapiens (human)Ki70.00000.00031.684210.0000AID54405
UDP-glucuronosyltransferase 2B7Homo sapiens (human)IC50 (µMol)296.20000.10002.50004.9000AID1802994
UDP-glucuronosyltransferase 1-6Homo sapiens (human)IC50 (µMol)296.20004.90004.90004.9000AID1802994
UDP-glucuronosyltransferase 1A1 Homo sapiens (human)IC50 (µMol)296.20000.30003.25807.3000AID1802994
UDP-glucuronosyltransferase 1A4Homo sapiens (human)IC50 (µMol)296.20004.72004.81004.9000AID1802994
UDP-glucuronosyltransferase 2B10 Homo sapiens (human)IC50 (µMol)296.20004.90004.90004.9000AID1802994
Lanosterol 14-alpha demethylaseHomo sapiens (human)IC50 (µMol)200.00000.05001.43904.0000AID322753
Canalicular multispecific organic anion transporter 1Homo sapiens (human)IC50 (µMol)133.00002.41006.343310.0000AID1473739
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Potassium channel subfamily K member 2Homo sapiens (human)EC50 (µMol)784.00000.18702.72248.1800AID1802150
AlbuminHomo sapiens (human)Kd6.02560.08933.31358.0000AID327170
AlbuminRattus norvegicus (Norway rat)Kd7.97001.47006.53179.3100AID1215123
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (142)

Processvia Protein(s)Taxonomy
xenobiotic metabolic processATP-binding cassette sub-family C member 3Homo sapiens (human)
xenobiotic transmembrane transportATP-binding cassette sub-family C member 3Homo sapiens (human)
bile acid and bile salt transportATP-binding cassette sub-family C member 3Homo sapiens (human)
glucuronoside transportATP-binding cassette sub-family C member 3Homo sapiens (human)
xenobiotic transportATP-binding cassette sub-family C member 3Homo sapiens (human)
transmembrane transportATP-binding cassette sub-family C member 3Homo sapiens (human)
leukotriene transportATP-binding cassette sub-family C member 3Homo sapiens (human)
monoatomic anion transmembrane transportATP-binding cassette sub-family C member 3Homo sapiens (human)
transport across blood-brain barrierATP-binding cassette sub-family C member 3Homo sapiens (human)
prostaglandin secretionMultidrug resistance-associated protein 4Homo sapiens (human)
cilium assemblyMultidrug resistance-associated protein 4Homo sapiens (human)
platelet degranulationMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic metabolic processMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
bile acid and bile salt transportMultidrug resistance-associated protein 4Homo sapiens (human)
prostaglandin transportMultidrug resistance-associated protein 4Homo sapiens (human)
urate transportMultidrug resistance-associated protein 4Homo sapiens (human)
glutathione transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
cAMP transportMultidrug resistance-associated protein 4Homo sapiens (human)
leukotriene transportMultidrug resistance-associated protein 4Homo sapiens (human)
monoatomic anion transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
export across plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
transport across blood-brain barrierMultidrug resistance-associated protein 4Homo sapiens (human)
guanine nucleotide transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
cardiac ventricle developmentPotassium channel subfamily K member 2Homo sapiens (human)
G protein-coupled receptor signaling pathwayPotassium channel subfamily K member 2Homo sapiens (human)
memoryPotassium channel subfamily K member 2Homo sapiens (human)
response to mechanical stimulusPotassium channel subfamily K member 2Homo sapiens (human)
response to axon injuryPotassium channel subfamily K member 2Homo sapiens (human)
negative regulation of cardiac muscle cell proliferationPotassium channel subfamily K member 2Homo sapiens (human)
cellular response to hypoxiaPotassium channel subfamily K member 2Homo sapiens (human)
potassium ion transmembrane transportPotassium channel subfamily K member 2Homo sapiens (human)
cochlea developmentPotassium channel subfamily K member 2Homo sapiens (human)
positive regulation of cellular response to hypoxiaPotassium channel subfamily K member 2Homo sapiens (human)
negative regulation of DNA biosynthetic processPotassium channel subfamily K member 2Homo sapiens (human)
stabilization of membrane potentialPotassium channel subfamily K member 2Homo sapiens (human)
fatty acid metabolic processBile salt export pumpHomo sapiens (human)
bile acid biosynthetic processBile salt export pumpHomo sapiens (human)
xenobiotic metabolic processBile salt export pumpHomo sapiens (human)
xenobiotic transmembrane transportBile salt export pumpHomo sapiens (human)
response to oxidative stressBile salt export pumpHomo sapiens (human)
bile acid metabolic processBile salt export pumpHomo sapiens (human)
response to organic cyclic compoundBile salt export pumpHomo sapiens (human)
bile acid and bile salt transportBile salt export pumpHomo sapiens (human)
canalicular bile acid transportBile salt export pumpHomo sapiens (human)
protein ubiquitinationBile salt export pumpHomo sapiens (human)
regulation of fatty acid beta-oxidationBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transportBile salt export pumpHomo sapiens (human)
bile acid signaling pathwayBile salt export pumpHomo sapiens (human)
cholesterol homeostasisBile salt export pumpHomo sapiens (human)
response to estrogenBile salt export pumpHomo sapiens (human)
response to ethanolBile salt export pumpHomo sapiens (human)
xenobiotic export from cellBile salt export pumpHomo sapiens (human)
lipid homeostasisBile salt export pumpHomo sapiens (human)
phospholipid homeostasisBile salt export pumpHomo sapiens (human)
positive regulation of bile acid secretionBile salt export pumpHomo sapiens (human)
regulation of bile acid metabolic processBile salt export pumpHomo sapiens (human)
transmembrane transportBile salt export pumpHomo sapiens (human)
cell surface receptor signaling pathway via JAK-STATInterferon betaHomo sapiens (human)
response to exogenous dsRNAInterferon betaHomo sapiens (human)
B cell activation involved in immune responseInterferon betaHomo sapiens (human)
cell surface receptor signaling pathwayInterferon betaHomo sapiens (human)
cell surface receptor signaling pathway via JAK-STATInterferon betaHomo sapiens (human)
response to virusInterferon betaHomo sapiens (human)
positive regulation of autophagyInterferon betaHomo sapiens (human)
cytokine-mediated signaling pathwayInterferon betaHomo sapiens (human)
natural killer cell activationInterferon betaHomo sapiens (human)
positive regulation of peptidyl-serine phosphorylation of STAT proteinInterferon betaHomo sapiens (human)
cellular response to interferon-betaInterferon betaHomo sapiens (human)
B cell proliferationInterferon betaHomo sapiens (human)
negative regulation of viral genome replicationInterferon betaHomo sapiens (human)
innate immune responseInterferon betaHomo sapiens (human)
positive regulation of innate immune responseInterferon betaHomo sapiens (human)
regulation of MHC class I biosynthetic processInterferon betaHomo sapiens (human)
negative regulation of T cell differentiationInterferon betaHomo sapiens (human)
positive regulation of transcription by RNA polymerase IIInterferon betaHomo sapiens (human)
defense response to virusInterferon betaHomo sapiens (human)
type I interferon-mediated signaling pathwayInterferon betaHomo sapiens (human)
neuron cellular homeostasisInterferon betaHomo sapiens (human)
cellular response to exogenous dsRNAInterferon betaHomo sapiens (human)
cellular response to virusInterferon betaHomo sapiens (human)
negative regulation of Lewy body formationInterferon betaHomo sapiens (human)
negative regulation of T-helper 2 cell cytokine productionInterferon betaHomo sapiens (human)
positive regulation of apoptotic signaling pathwayInterferon betaHomo sapiens (human)
response to exogenous dsRNAInterferon betaHomo sapiens (human)
B cell differentiationInterferon betaHomo sapiens (human)
natural killer cell activation involved in immune responseInterferon betaHomo sapiens (human)
adaptive immune responseInterferon betaHomo sapiens (human)
T cell activation involved in immune responseInterferon betaHomo sapiens (human)
humoral immune responseInterferon betaHomo sapiens (human)
positive regulation of T cell mediated cytotoxicityHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
adaptive immune responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independentHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of T cell anergyHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
defense responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
immune responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
detection of bacteriumHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of interleukin-12 productionHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of interleukin-6 productionHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
protection from natural killer cell mediated cytotoxicityHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
innate immune responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of dendritic cell differentiationHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
antigen processing and presentation of endogenous peptide antigen via MHC class IbHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
cellular response to starvationAlbuminHomo sapiens (human)
negative regulation of mitochondrial depolarizationAlbuminHomo sapiens (human)
cellular response to calcium ion starvationAlbuminHomo sapiens (human)
cellular oxidant detoxificationAlbuminHomo sapiens (human)
transportAlbuminHomo sapiens (human)
xenobiotic metabolic processCytochrome P450 2C9 Homo sapiens (human)
steroid metabolic processCytochrome P450 2C9 Homo sapiens (human)
cholesterol metabolic processCytochrome P450 2C9 Homo sapiens (human)
estrogen metabolic processCytochrome P450 2C9 Homo sapiens (human)
monoterpenoid metabolic processCytochrome P450 2C9 Homo sapiens (human)
epoxygenase P450 pathwayCytochrome P450 2C9 Homo sapiens (human)
urea metabolic processCytochrome P450 2C9 Homo sapiens (human)
monocarboxylic acid metabolic processCytochrome P450 2C9 Homo sapiens (human)
xenobiotic catabolic processCytochrome P450 2C9 Homo sapiens (human)
long-chain fatty acid biosynthetic processCytochrome P450 2C9 Homo sapiens (human)
amide metabolic processCytochrome P450 2C9 Homo sapiens (human)
icosanoid biosynthetic processCytochrome P450 2C9 Homo sapiens (human)
oxidative demethylationCytochrome P450 2C9 Homo sapiens (human)
omega-hydroxylase P450 pathwayCytochrome P450 2C9 Homo sapiens (human)
lipid metabolic processUDP-glucuronosyltransferase 2B7Homo sapiens (human)
xenobiotic metabolic processUDP-glucuronosyltransferase 2B7Homo sapiens (human)
androgen metabolic processUDP-glucuronosyltransferase 2B7Homo sapiens (human)
estrogen metabolic processUDP-glucuronosyltransferase 2B7Homo sapiens (human)
cellular glucuronidationUDP-glucuronosyltransferase 2B7Homo sapiens (human)
xenobiotic metabolic processUDP-glucuronosyltransferase 1-6Homo sapiens (human)
cellular glucuronidationUDP-glucuronosyltransferase 1-6Homo sapiens (human)
liver developmentUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
bilirubin conjugationUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
xenobiotic metabolic processUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
acute-phase responseUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
response to nutrientUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
steroid metabolic processUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
estrogen metabolic processUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
animal organ regenerationUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
response to lipopolysaccharideUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
retinoic acid metabolic processUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
response to starvationUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
negative regulation of steroid metabolic processUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
flavone metabolic processUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
cellular glucuronidationUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
flavonoid glucuronidationUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
xenobiotic glucuronidationUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
biphenyl catabolic processUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
cellular response to ethanolUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
cellular response to glucocorticoid stimulusUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
cellular response to estradiol stimulusUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
bilirubin conjugationUDP-glucuronosyltransferase 1A4Homo sapiens (human)
heme catabolic processUDP-glucuronosyltransferase 1A4Homo sapiens (human)
cellular glucuronidationUDP-glucuronosyltransferase 1A4Homo sapiens (human)
vitamin D3 metabolic processUDP-glucuronosyltransferase 1A4Homo sapiens (human)
lipid metabolic processUDP-glucuronosyltransferase 2B10 Homo sapiens (human)
cellular glucuronidationUDP-glucuronosyltransferase 2B10 Homo sapiens (human)
estrogen metabolic processUDP-glucuronosyltransferase 2B10 Homo sapiens (human)
steroid biosynthetic processLanosterol 14-alpha demethylaseHomo sapiens (human)
cholesterol biosynthetic processLanosterol 14-alpha demethylaseHomo sapiens (human)
sterol metabolic processLanosterol 14-alpha demethylaseHomo sapiens (human)
negative regulation of protein catabolic processLanosterol 14-alpha demethylaseHomo sapiens (human)
negative regulation of protein secretionLanosterol 14-alpha demethylaseHomo sapiens (human)
negative regulation of amyloid-beta clearanceLanosterol 14-alpha demethylaseHomo sapiens (human)
inositol phosphate metabolic processInositol hexakisphosphate kinase 1Homo sapiens (human)
phosphatidylinositol phosphate biosynthetic processInositol hexakisphosphate kinase 1Homo sapiens (human)
negative regulation of cold-induced thermogenesisInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol phosphate biosynthetic processInositol hexakisphosphate kinase 1Homo sapiens (human)
xenobiotic metabolic processCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic transmembrane transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
negative regulation of gene expressionCanalicular multispecific organic anion transporter 1Homo sapiens (human)
bile acid and bile salt transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
bilirubin transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
heme catabolic processCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic export from cellCanalicular multispecific organic anion transporter 1Homo sapiens (human)
transmembrane transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
transepithelial transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
leukotriene transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
monoatomic anion transmembrane transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
transport across blood-brain barrierCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic transport across blood-brain barrierCanalicular multispecific organic anion transporter 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (75)

Processvia Protein(s)Taxonomy
ATP bindingATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type xenobiotic transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
glucuronoside transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type bile acid transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ATP hydrolysis activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ATPase-coupled transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
xenobiotic transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
icosanoid transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
guanine nucleotide transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
protein bindingMultidrug resistance-associated protein 4Homo sapiens (human)
ATP bindingMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type xenobiotic transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
prostaglandin transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
urate transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
purine nucleotide transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type bile acid transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
efflux transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
15-hydroxyprostaglandin dehydrogenase (NAD+) activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATP hydrolysis activityMultidrug resistance-associated protein 4Homo sapiens (human)
glutathione transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATPase-coupled transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
outward rectifier potassium channel activityPotassium channel subfamily K member 2Homo sapiens (human)
potassium ion leak channel activityPotassium channel subfamily K member 2Homo sapiens (human)
protein bindingBile salt export pumpHomo sapiens (human)
ATP bindingBile salt export pumpHomo sapiens (human)
ABC-type xenobiotic transporter activityBile salt export pumpHomo sapiens (human)
bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
canalicular bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transporter activityBile salt export pumpHomo sapiens (human)
ABC-type bile acid transporter activityBile salt export pumpHomo sapiens (human)
ATP hydrolysis activityBile salt export pumpHomo sapiens (human)
cytokine activityInterferon betaHomo sapiens (human)
cytokine receptor bindingInterferon betaHomo sapiens (human)
type I interferon receptor bindingInterferon betaHomo sapiens (human)
protein bindingInterferon betaHomo sapiens (human)
chloramphenicol O-acetyltransferase activityInterferon betaHomo sapiens (human)
TAP bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
signaling receptor bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
protein bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
peptide antigen bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
TAP bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
protein-folding chaperone bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
oxygen bindingAlbuminHomo sapiens (human)
DNA bindingAlbuminHomo sapiens (human)
fatty acid bindingAlbuminHomo sapiens (human)
copper ion bindingAlbuminHomo sapiens (human)
protein bindingAlbuminHomo sapiens (human)
toxic substance bindingAlbuminHomo sapiens (human)
antioxidant activityAlbuminHomo sapiens (human)
pyridoxal phosphate bindingAlbuminHomo sapiens (human)
identical protein bindingAlbuminHomo sapiens (human)
protein-folding chaperone bindingAlbuminHomo sapiens (human)
exogenous protein bindingAlbuminHomo sapiens (human)
enterobactin bindingAlbuminHomo sapiens (human)
monooxygenase activityCytochrome P450 2C9 Homo sapiens (human)
iron ion bindingCytochrome P450 2C9 Homo sapiens (human)
arachidonic acid epoxygenase activityCytochrome P450 2C9 Homo sapiens (human)
steroid hydroxylase activityCytochrome P450 2C9 Homo sapiens (human)
arachidonic acid 14,15-epoxygenase activityCytochrome P450 2C9 Homo sapiens (human)
arachidonic acid 11,12-epoxygenase activityCytochrome P450 2C9 Homo sapiens (human)
oxidoreductase activityCytochrome P450 2C9 Homo sapiens (human)
(S)-limonene 6-monooxygenase activityCytochrome P450 2C9 Homo sapiens (human)
(S)-limonene 7-monooxygenase activityCytochrome P450 2C9 Homo sapiens (human)
caffeine oxidase activityCytochrome P450 2C9 Homo sapiens (human)
(R)-limonene 6-monooxygenase activityCytochrome P450 2C9 Homo sapiens (human)
aromatase activityCytochrome P450 2C9 Homo sapiens (human)
heme bindingCytochrome 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 oxygenCytochrome P450 2C9 Homo sapiens (human)
retinoic acid bindingUDP-glucuronosyltransferase 2B7Homo sapiens (human)
glucuronosyltransferase activityUDP-glucuronosyltransferase 2B7Homo sapiens (human)
retinoic acid bindingUDP-glucuronosyltransferase 1-6Homo sapiens (human)
glucuronosyltransferase activityUDP-glucuronosyltransferase 1-6Homo sapiens (human)
enzyme bindingUDP-glucuronosyltransferase 1-6Homo sapiens (human)
protein homodimerization activityUDP-glucuronosyltransferase 1-6Homo sapiens (human)
protein heterodimerization activityUDP-glucuronosyltransferase 1-6Homo sapiens (human)
retinoic acid bindingUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
enzyme inhibitor activityUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
steroid bindingUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
glucuronosyltransferase activityUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
enzyme bindingUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
protein homodimerization activityUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
protein heterodimerization activityUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
retinoic acid bindingUDP-glucuronosyltransferase 1A4Homo sapiens (human)
glucuronosyltransferase activityUDP-glucuronosyltransferase 1A4Homo sapiens (human)
enzyme bindingUDP-glucuronosyltransferase 1A4Homo sapiens (human)
protein homodimerization activityUDP-glucuronosyltransferase 1A4Homo sapiens (human)
protein heterodimerization activityUDP-glucuronosyltransferase 1A4Homo sapiens (human)
glucuronosyltransferase activityUDP-glucuronosyltransferase 2B10 Homo sapiens (human)
UDP-glycosyltransferase activityUDP-glucuronosyltransferase 2B10 Homo sapiens (human)
iron ion bindingLanosterol 14-alpha demethylaseHomo sapiens (human)
sterol 14-demethylase activityLanosterol 14-alpha demethylaseHomo sapiens (human)
heme bindingLanosterol 14-alpha demethylaseHomo sapiens (human)
oxidoreductase activityLanosterol 14-alpha demethylaseHomo 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 oxygenLanosterol 14-alpha demethylaseHomo sapiens (human)
inositol-1,3,4,5,6-pentakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol heptakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate 5-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
protein bindingInositol hexakisphosphate kinase 1Homo sapiens (human)
ATP bindingInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate 1-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate 3-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol 5-diphosphate pentakisphosphate 5-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol diphosphate tetrakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
protein bindingCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATP bindingCanalicular multispecific organic anion transporter 1Homo sapiens (human)
organic anion transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ABC-type xenobiotic transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
bilirubin transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATP hydrolysis activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATPase-coupled transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ABC-type transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (45)

Processvia Protein(s)Taxonomy
plasma membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
basal plasma membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
basolateral plasma membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
nucleolusMultidrug resistance-associated protein 4Homo sapiens (human)
Golgi apparatusMultidrug resistance-associated protein 4Homo sapiens (human)
plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
membraneMultidrug resistance-associated protein 4Homo sapiens (human)
basolateral plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
apical plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
platelet dense granule membraneMultidrug resistance-associated protein 4Homo sapiens (human)
external side of apical plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
endoplasmic reticulum membranePotassium channel subfamily K member 2Homo sapiens (human)
plasma membranePotassium channel subfamily K member 2Homo sapiens (human)
cell surfacePotassium channel subfamily K member 2Homo sapiens (human)
apical plasma membranePotassium channel subfamily K member 2Homo sapiens (human)
neuronal cell bodyPotassium channel subfamily K member 2Homo sapiens (human)
calyx of HeldPotassium channel subfamily K member 2Homo sapiens (human)
astrocyte projectionPotassium channel subfamily K member 2Homo sapiens (human)
voltage-gated potassium channel complexPotassium channel subfamily K member 2Homo sapiens (human)
plasma membranePotassium channel subfamily K member 2Homo sapiens (human)
basolateral plasma membraneBile salt export pumpHomo sapiens (human)
Golgi membraneBile salt export pumpHomo sapiens (human)
endosomeBile salt export pumpHomo sapiens (human)
plasma membraneBile salt export pumpHomo sapiens (human)
cell surfaceBile salt export pumpHomo sapiens (human)
apical plasma membraneBile salt export pumpHomo sapiens (human)
intercellular canaliculusBile salt export pumpHomo sapiens (human)
intracellular canaliculusBile salt export pumpHomo sapiens (human)
recycling endosomeBile salt export pumpHomo sapiens (human)
recycling endosome membraneBile salt export pumpHomo sapiens (human)
extracellular exosomeBile salt export pumpHomo sapiens (human)
membraneBile salt export pumpHomo sapiens (human)
extracellular spaceInterferon betaHomo sapiens (human)
extracellular regionInterferon betaHomo sapiens (human)
Golgi membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
endoplasmic reticulumHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
Golgi apparatusHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
plasma membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
cell surfaceHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
ER to Golgi transport vesicle membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
secretory granule membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
phagocytic vesicle membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
early endosome membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
recycling endosome membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
extracellular exosomeHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
lumenal side of endoplasmic reticulum membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
MHC class I protein complexHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
extracellular spaceHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
external side of plasma membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
extracellular regionAlbuminHomo sapiens (human)
extracellular spaceAlbuminHomo sapiens (human)
nucleusAlbuminHomo sapiens (human)
endoplasmic reticulumAlbuminHomo sapiens (human)
endoplasmic reticulum lumenAlbuminHomo sapiens (human)
Golgi apparatusAlbuminHomo sapiens (human)
platelet alpha granule lumenAlbuminHomo sapiens (human)
extracellular exosomeAlbuminHomo sapiens (human)
blood microparticleAlbuminHomo sapiens (human)
protein-containing complexAlbuminHomo sapiens (human)
cytoplasmAlbuminHomo sapiens (human)
endoplasmic reticulum membraneCytochrome P450 2C9 Homo sapiens (human)
plasma membraneCytochrome P450 2C9 Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 2C9 Homo sapiens (human)
cytoplasmCytochrome P450 2C9 Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 2C9 Homo sapiens (human)
endoplasmic reticulum membraneUDP-glucuronosyltransferase 2B7Homo sapiens (human)
membraneUDP-glucuronosyltransferase 2B7Homo sapiens (human)
endoplasmic reticulumUDP-glucuronosyltransferase 1-6Homo sapiens (human)
endoplasmic reticulum membraneUDP-glucuronosyltransferase 1-6Homo sapiens (human)
intracellular membrane-bounded organelleUDP-glucuronosyltransferase 1-6Homo sapiens (human)
endoplasmic reticulumUDP-glucuronosyltransferase 1-6Homo sapiens (human)
endoplasmic reticulumUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
endoplasmic reticulum membraneUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
plasma membraneUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
perinuclear region of cytoplasmUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
endoplasmic reticulum chaperone complexUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
cytochrome complexUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
endoplasmic reticulumUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
endoplasmic reticulumUDP-glucuronosyltransferase 1A4Homo sapiens (human)
endoplasmic reticulum membraneUDP-glucuronosyltransferase 1A4Homo sapiens (human)
endoplasmic reticulumUDP-glucuronosyltransferase 1A4Homo sapiens (human)
endoplasmic reticulum membraneUDP-glucuronosyltransferase 2B10 Homo sapiens (human)
endoplasmic reticulum membraneLanosterol 14-alpha demethylaseHomo sapiens (human)
membraneLanosterol 14-alpha demethylaseHomo sapiens (human)
fibrillar centerInositol hexakisphosphate kinase 1Homo sapiens (human)
nucleoplasmInositol hexakisphosphate kinase 1Homo sapiens (human)
cytosolInositol hexakisphosphate kinase 1Homo sapiens (human)
nucleusInositol hexakisphosphate kinase 1Homo sapiens (human)
cytoplasmInositol hexakisphosphate kinase 1Homo sapiens (human)
plasma membraneCanalicular multispecific organic anion transporter 1Homo sapiens (human)
cell surfaceCanalicular multispecific organic anion transporter 1Homo sapiens (human)
apical plasma membraneCanalicular multispecific organic anion transporter 1Homo sapiens (human)
intercellular canaliculusCanalicular multispecific organic anion transporter 1Homo sapiens (human)
apical plasma membraneCanalicular multispecific organic anion transporter 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (304)

Assay IDTitleYearJournalArticle
AID540299A screen for compounds that inhibit the MenB enzyme of Mycobacterium tuberculosis2010Bioorganic & medicinal chemistry letters, Nov-01, Volume: 20, Issue:21
Synthesis and SAR studies of 1,4-benzoxazine MenB inhibitors: novel antibacterial agents against Mycobacterium tuberculosis.
AID588519A screen for compounds that inhibit viral RNA polymerase binding and polymerization activities2011Antiviral research, Sep, Volume: 91, Issue:3
High-throughput screening identification of poliovirus RNA-dependent RNA polymerase inhibitors.
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID588378qHTS for Inhibitors of ATXN expression: Validation
AID504836Inducers of the Endoplasmic Reticulum Stress Response (ERSR) in human glioma: Validation2002The 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.
AID1347082qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID504812Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID1347410qHTS for inhibitors of adenylyl cyclases using a fission yeast platform: a pilot screen against the NCATS LOPAC library2019Cellular signalling, 08, Volume: 60A fission yeast platform for heterologous expression of mammalian adenylyl cyclases and high throughput screening.
AID504810Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID1347083qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347045Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot counterscreen GloSensor control cell line2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID588349qHTS for Inhibitors of ATXN expression: Validation of Cytotoxic Assay
AID1508630Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347058CD47-SIRPalpha protein protein interaction - HTRF assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347151Optimization of GU AMC qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings 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.
AID1347050Natriuretic polypeptide receptor (hNpr2) antagonism - Pilot subtype selectivity assay2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID1347086qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347405qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS LOPAC collection2020ACS 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.
AID1347057CD47-SIRPalpha protein protein interaction - LANCE assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347049Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot screen2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID1347059CD47-SIRPalpha protein protein interaction - Alpha assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID625277FDA Liver Toxicity Knowledge Base Benchmark Dataset (LTKB-BD) drugs of less concern for DILI2011Drug discovery today, Aug, Volume: 16, Issue:15-16
FDA-approved drug labeling for the study of drug-induced liver injury.
AID444055Fraction absorbed in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID300390Effect on insulin secretion activity per ug of total protein in rat RIN5F cells at 1 uM after 30 mins2007Bioorganic & medicinal chemistry, Sep-01, Volume: 15, Issue:17
Synthesis of 3,8,9-trisubstituted-1,7,9-triaza-fluorene-6-carboxylic acid derivatives as a new class of insulin secretagogues.
AID1211793Lipophilicity, log P of the compound2012Drug 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.
AID625282Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cirrhosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID702034Induction of glucose-stimulated insulin release from rat INS-1E cells at 200 uM after 1 hr by coated charcoal immunoassay in presence of 11 mM glucose2012Bioorganic & medicinal chemistry letters, Jun-01, Volume: 22, Issue:11
Synthesis and preliminary biological profile of new NO-donor tolbutamide analogues.
AID496832Antimicrobial activity against Trypanosoma brucei rhodesiense2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID496829Antimicrobial activity against Leishmania infantum2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID310933Permeability across PAMPA membrane after 7 hrs2007Journal of medicinal chemistry, Feb-22, Volume: 50, Issue:4
In silico and in vitro filters for the fast estimation of skin permeation and distribution of new chemical entities.
AID29811Oral bioavailability in human2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID277377Inhibition of increase in serum glucose level in sucrose-loaded Wistar rat at 12.5 mg/kg, po after 1hr2007Journal of natural products, Feb, Volume: 70, Issue:2
Structures of steroidal alkaloid oligoglycosides, robeneosides A and B, and antidiabetogenic constituents from the Brazilian medicinal plant Solanum lycocarpum.
AID521220Inhibition of neurosphere proliferation of mouse neural precursor cells by MTT assay2007Nature chemical biology, May, Volume: 3, Issue:5
Chemical genetics reveals a complex functional ground state of neural stem cells.
AID702021Vasodilatory activity in Wistar rat thoracic aorta assessed as relaxation of L-phenylephrine-induced contraction after 120 mins in presence of 1 uM sGC inhibitor ODQ2012Bioorganic & medicinal chemistry letters, Jun-01, Volume: 22, Issue:11
Synthesis and preliminary biological profile of new NO-donor tolbutamide analogues.
AID172902Percent change in blood glucose in normal rats at a hypoglycemic dose of 0.17 mmol/kg. against control1983Journal of medicinal chemistry, Jul, Volume: 26, Issue:7
Sulfonyliminoimidazolidines. A new class of oral hypoglycemic agents. 2. Mode of action and X-ray structure of 1-[[p-[2-(crotonylamino)ethyl]phenyl]sulfonyl]-3-cyclohexyl-2-iminoimidazolidine.
AID173800Compound evaluated for hypoglycemic activity by lowering blood glucose in streptozotocin-diabetic rats by 20% after oral administration; Inactive(less than 10% blood sugar decrease)1983Journal of medicinal chemistry, Jul, Volume: 26, Issue:7
Sulfonyliminoimidazolidines. A new class of oral hypoglycemic agents. 1. 1-[[p-[2-(acylamino)ethyl]phenyl]sulfonyl]-2-iminoimidazolidines.
AID625287Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatomegaly2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID301100Insulinotropic activity in rat RIN5F cells assessed as glucose dependent insulin secretion per ug of total protein at 10 uM2007Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21
Synthesis and antidiabetic activity of 2,5-disubstituted-3-imidazol-2-yl-pyrrolo[2,3-b]pyridines and thieno[2,3-b]pyridines.
AID702031Induction of glucose-stimulated insulin release from rat INS-1E cells at 100 uM after 1 hr by coated charcoal immunoassay in presence of 2 mM glucose relative to control2012Bioorganic & medicinal chemistry letters, Jun-01, Volume: 22, Issue:11
Synthesis and preliminary biological profile of new NO-donor tolbutamide analogues.
AID1636356Drug 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 NA2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
Development of a cell viability assay to assess drug metabolite structure-toxicity relationships.
AID300392Effect on glucose-dependent insulin secretion activity per ug of total protein in rat RIN5F cells at 1 uM after 30 mins2007Bioorganic & medicinal chemistry, Sep-01, Volume: 15, Issue:17
Synthesis of 3,8,9-trisubstituted-1,7,9-triaza-fluorene-6-carboxylic acid derivatives as a new class of insulin secretagogues.
AID497005Antimicrobial activity against Pneumocystis carinii2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID588211Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in humans2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID1589471Antihyperglycemic activity in alloxanized BALB/c mouse model of diabetes assessed as blood glucose level at 150 mg/kg, po measured after 2 hrs (Rvb = 217 +/ - 3.2)2019European journal of medicinal chemistry, Apr-15, Volume: 168Synthesis of new arylsulfonylspiroimidazolidine-2',4'-diones and study of their effect on stimulation of insulin release from MIN6 cell line, inhibition of human aldose reductase, sorbitol accumulations in various tissues and oxidative stress.
AID515780Intrinsic solubility of the compound in water2010Bioorganic & medicinal chemistry, Oct-01, Volume: 18, Issue:19
QSAR-based solubility model for drug-like compounds.
AID496820Antimicrobial activity against Trypanosoma brucei2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID496823Antimicrobial activity against Trichomonas vaginalis2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1124414Hypoglycemic activity in 48 hrs fasted Charles River rat at 200 mg/kg, po measured at 2 hrs relative to control1979Journal of medicinal chemistry, Jul, Volume: 22, Issue:7
Synthesis and hypoglycemic activity of pyridyl alcohols.
AID322753Inhibition of human CYP51 expressed in Topp 3 cells by lanosterol demethylase assay2007Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 35, Issue:3
Three-dimensional quantitative structure-activity relationship analysis of human CYP51 inhibitors.
AID402157Hypoglycemic activity in diabetic KK-Ay mouse at 50 mg/kg, ip assessed as blood glucose level per 100 mL blood after 7 hrs1997Journal of natural products, Jun, Volume: 60, Issue:6
Hypoglycemic activity of some triterpenoid glycosides.
AID444050Fraction unbound in human plasma2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1079935Cytolytic 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]
AID402222Hypoglycemic activity in 16 hrs fasted Wistar rat assessed as reduction in serum glucose level at 100 mg/kg, po measured after 30 mins of glucose challenge by oral glucose tolerance test2004Journal of natural products, May, Volume: 67, Issue:5
Hypoglycemic effect and antioxidant potential of kaempferol-3,7-O-(alpha)-dirhamnoside from Bauhinia forficata leaves.
AID496825Antimicrobial activity against Leishmania mexicana2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID166779In vitro insulin release was stimulated by the compound at a concentration of 0.01 mmol/L in rabbit pancreas1983Journal of medicinal chemistry, Jul, Volume: 26, Issue:7
Sulfonyliminoimidazolidines. A new class of oral hypoglycemic agents. 2. Mode of action and X-ray structure of 1-[[p-[2-(crotonylamino)ethyl]phenyl]sulfonyl]-3-cyclohexyl-2-iminoimidazolidine.
AID702032Induction of glucose-stimulated insulin release from rat INS-1E cells at 200 uM after 1 hr by coated charcoal immunoassay in presence of up to 4 mM glucose2012Bioorganic & medicinal chemistry letters, Jun-01, Volume: 22, Issue:11
Synthesis and preliminary biological profile of new NO-donor tolbutamide analogues.
AID399320Hypoglycemic activity in fasting rabbit assessed as reduction of plasma glucose at 50 mg/kg, po
AID699540Inhibition 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 counting2012Journal 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.
AID1311584Drug uptake in mouse hepatocytes measured at 30 secs relative to control2016Bioorganic & medicinal chemistry letters, 08-01, Volume: 26, Issue:15
Synthesis and evaluation of a series of 4-azaindole-containing p21-activated kinase-1 inhibitors.
AID28681Partition coefficient (logD6.5)2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID496827Antimicrobial activity against Leishmania amazonensis2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1211794Fraction unbound in blood (not specified)2012Drug 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.
AID186643In vitro inhibition of glucose oxidation determined in normal rats at a hypoglycemic dose of 0.17 mmol/kg.1983Journal of medicinal chemistry, Jul, Volume: 26, Issue:7
Sulfonyliminoimidazolidines. A new class of oral hypoglycemic agents. 2. Mode of action and X-ray structure of 1-[[p-[2-(crotonylamino)ethyl]phenyl]sulfonyl]-3-cyclohexyl-2-iminoimidazolidine.
AID1209455Inhibition of human BSEP expressed in plasma membrane vesicles of Sf21 cells assessed as inhibition of ATP-dependent [3H]taurocholate uptake2012Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 40, Issue:1
In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans.
AID399332Hypoglycemic activity in rabbit assessed as reduction of plasma glucose at 50 mg/kg, po after 2 hrs
AID243230Binding affinity towards human serum albumin2005Journal of medicinal chemistry, Apr-07, Volume: 48, Issue:7
Predicting human serum albumin affinity of interleukin-8 (CXCL8) inhibitors by 3D-QSPR approach.
AID540213Half life in human after iv administration2008Drug 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.
AID373867Hepatic clearance in human hepatocytes in absence of fetal calf serum2009European journal of medicinal chemistry, Apr, Volume: 44, Issue:4
First-principle, structure-based prediction of hepatic metabolic clearance values in human.
AID301106Insulinotropic activity in rat RIN5F cells assessed as insulin secretion per ug of total protein at 1 uM2007Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21
Synthesis and antidiabetic activity of 2,5-disubstituted-3-imidazol-2-yl-pyrrolo[2,3-b]pyridines and thieno[2,3-b]pyridines.
AID399327Hypoglycemic activity in glucose-fed rabbit assessed as reduction of plasma glucose at 50 mg/kg, po after 0.5 hr
AID540210Clearance in human after iv administration2008Drug 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.
AID453203Lipophilicity, log D of the compound2010Bioorganic & 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.
AID1473741Inhibition 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 assay2013Toxicological 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.
AID702033Induction of glucose-stimulated insulin release from rat INS-1E cells at 200 uM after 1 hr by coated charcoal immunoassay in presence of 5.6 mM glucose2012Bioorganic & medicinal chemistry letters, Jun-01, Volume: 22, Issue:11
Synthesis and preliminary biological profile of new NO-donor tolbutamide analogues.
AID702020Vasodilatory activity in Wistar rat thoracic aorta assessed as relaxation of L-phenylephrine-induced contraction after 120 mins2012Bioorganic & medicinal chemistry letters, Jun-01, Volume: 22, Issue:11
Synthesis and preliminary biological profile of new NO-donor tolbutamide analogues.
AID496818Antimicrobial activity against Trypanosoma brucei brucei2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID1652312Inhibition of human CYP2C9 at 10 uM2020Journal of medicinal chemistry, 07-09, Volume: 63, Issue:13
Novel Pyrrolopyridone Bromodomain and Extra-Terminal Motif (BET) Inhibitors Effective in Endocrine-Resistant ER+ Breast Cancer with Acquired Resistance to Fulvestrant and Palbociclib.
AID310931Partition coefficient, log P of the compound2007Journal of medicinal chemistry, Feb-22, Volume: 50, Issue:4
In silico and in vitro filters for the fast estimation of skin permeation and distribution of new chemical entities.
AID444053Renal clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1079931Moderate 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]
AID496831Antimicrobial activity against Cryptosporidium parvum2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID476929Human intestinal absorption in po dosed human2010European journal of medicinal chemistry, Mar, Volume: 45, Issue:3
Neural computational prediction of oral drug absorption based on CODES 2D descriptors.
AID54405Binding affinity measured on human cytochrome P450 2C9 (CYP2C9) enzyme2000Journal of medicinal chemistry, Jul-27, Volume: 43, Issue:15
A refined 3-dimensional QSAR of cytochrome P450 2C9: computational predictions of drug interactions.
AID444058Volume of distribution at steady state in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID300389Effect on insulin secretion activity per ug of total protein in rat RIN5F cells at 0.1 uM after 30 mins2007Bioorganic & medicinal chemistry, Sep-01, Volume: 15, Issue:17
Synthesis of 3,8,9-trisubstituted-1,7,9-triaza-fluorene-6-carboxylic acid derivatives as a new class of insulin secretagogues.
AID327169Apparent permeability across parallel artificial membrane2008Journal of medicinal chemistry, Apr-10, Volume: 51, Issue:7
New approach to measure protein binding based on a parallel artificial membrane assay and human serum albumin.
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID1135171Hypoglycemic activity in 48 hrs fasted rat assessed as reduction in glucose level at 200 mg/kg, po measured after 2 hrs1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Synthesis and hypoglycemic activity of S-acyl derivatives of 3-mercaptopicolinic acid.
AID496824Antimicrobial activity against Toxoplasma gondii2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1215124Binding affinity to Wistar rat brain lipid assessed as percentage unbound by TRANSIL assay2011Drug metabolism and disposition: the biological fate of chemicals, Feb, Volume: 39, Issue:2
Brain tissue binding of drugs: evaluation and validation of solid supported porcine brain membrane vesicles (TRANSIL) as a novel high-throughput method.
AID1589435Antidiabetic activity in mouse MIN6 cells after 83 passages assessed as increase in insulin secretion at 100 uM in presence of 25 mM glucose by ELISA relative to control2019European journal of medicinal chemistry, Apr-15, Volume: 168Synthesis of new arylsulfonylspiroimidazolidine-2',4'-diones and study of their effect on stimulation of insulin release from MIN6 cell line, inhibition of human aldose reductase, sorbitol accumulations in various tissues and oxidative stress.
AID1145019Hypoglycemic activity in fasted glucose primed Sprague-Dawley rat assessed as plasma glucose level at 50 mg/kg administered via oral gavage measured after 2 hrs by glucose-oxidase method relative to control1976Journal of medicinal chemistry, Mar, Volume: 19, Issue:3
Hypoglycemic alpha-cycloalkylphenylmehtyl, furanalkyl, and thiophenealkyl lactamimides.
AID1589436Antidiabetic activity in mouse MIN6 cells after 35 passages assessed as increase in insulin secretion incubated for 48 hrs presence of 1 mM glucose by ELISA2019European journal of medicinal chemistry, Apr-15, Volume: 168Synthesis of new arylsulfonylspiroimidazolidine-2',4'-diones and study of their effect on stimulation of insulin release from MIN6 cell line, inhibition of human aldose reductase, sorbitol accumulations in various tissues and oxidative stress.
AID1079936Choleostatic 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]
AID467611Dissociation constant, pKa of the compound2009European 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.
AID588209Literature-mined public compounds from Greene et al multi-species hepatotoxicity modelling dataset2010Chemical research in toxicology, Jul-19, Volume: 23, Issue:7
Developing structure-activity relationships for the prediction of hepatotoxicity.
AID496821Antimicrobial activity against Leishmania2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID187237Hypoglycemic activity expressed as (Maximum reduction in blood glucose in mg/dL relative to predosing glucose level)/(time in hours at which maximum reduction occurred); 62/21990Journal of medicinal chemistry, Sep, Volume: 33, Issue:9
Novel agents effective against solid tumors: the diarylsulfonylureas. Synthesis, activities, and analysis of quantitative structure-activity relationships.
AID294990Insulinotropic activity in RIN5F cells assessed as stimulation of glucose-dependent insulin secretion per ug of protein at 0.1 uM2007Bioorganic & medicinal chemistry, May-01, Volume: 15, Issue:9
Design, synthesis, and biological evaluation of substituted-N-(thieno[2,3-b]pyridin-3-yl)-guanidines, N-(1H-pyrrolo[2,3-b]pyridin-3-yl)-guanidines, and N-(1H-indol-3-yl)-guanidines.
AID625280Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1209456Inhibition of Sprague-Dawley rat Bsep expressed in plasma membrane vesicles of Sf21 cells assessed as inhibition of ATP-dependent [3H]taurocholate uptake2012Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 40, Issue:1
In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans.
AID402225Hypoglycemic activity in 16 hrs fasted Wistar rat assessed as reduction in serum glucose level at 100 mg/kg, po measured after 180 mins of glucose challenge by oral glucose tolerance test2004Journal of natural products, May, Volume: 67, Issue:5
Hypoglycemic effect and antioxidant potential of kaempferol-3,7-O-(alpha)-dirhamnoside from Bauhinia forficata leaves.
AID679410TP_TRANSPORTER: uptake of Tolbutamide at a concentration of 8.82uM in OATP2B1-expressing HEK293 cells2005Drug metabolism and disposition: the biological fate of chemicals, Apr, Volume: 33, Issue:4
Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B.
AID1133996Hypoglycemic activity in 48-hrs fasted rat assessed as decrease in blood glucose level at 200 mg/kg, po after 2 hrs1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Mercapto heterocyclic carboxylic acids, analogues of 3-mercaptopicolinic acid.
AID1589473Antihyperglycemic activity in alloxanized BALB/c mouse model of diabetes assessed as blood glucose level at 150 mg/kg, po measured after 6 hrs (Rvb = 223 +/- 5.38)2019European journal of medicinal chemistry, Apr-15, Volume: 168Synthesis of new arylsulfonylspiroimidazolidine-2',4'-diones and study of their effect on stimulation of insulin release from MIN6 cell line, inhibition of human aldose reductase, sorbitol accumulations in various tissues and oxidative stress.
AID604744Displacement of radiolabeled dansylsarcosine from fatty acid containing human serum albumin site 2 in phosphate buffer at pH 7.4 at 12 uM by fluorescence spectroscopy2010Bioorganic & medicinal chemistry, Nov-01, Volume: 18, Issue:21
A combined spectroscopic and crystallographic approach to probing drug-human serum albumin interactions.
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID166783In vitro insulin release was stimulated by the compound at a concentration of 0.1 mmol/L in rabbit pancreas1983Journal of medicinal chemistry, Jul, Volume: 26, Issue:7
Sulfonyliminoimidazolidines. A new class of oral hypoglycemic agents. 2. Mode of action and X-ray structure of 1-[[p-[2-(crotonylamino)ethyl]phenyl]sulfonyl]-3-cyclohexyl-2-iminoimidazolidine.
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID402223Hypoglycemic activity in 16 hrs fasted Wistar rat assessed as reduction in serum glucose level at 100 mg/kg, po measured after 60 mins of glucose challenge by oral glucose tolerance test2004Journal of natural products, May, Volume: 67, Issue:5
Hypoglycemic effect and antioxidant potential of kaempferol-3,7-O-(alpha)-dirhamnoside from Bauhinia forficata leaves.
AID402151Hypoglycemic activity in normal ddY mouse at 50 mg/kg, ip assessed as blood glucose level per 100 mL blood after 7 hrs1997Journal of natural products, Jun, Volume: 60, Issue:6
Hypoglycemic activity of some triterpenoid glycosides.
AID277376Inhibition of increase in serum glucose level in sucrose-loaded Wistar rat at 12.5 mg/kg, po after 0.5 hrs2007Journal of natural products, Feb, Volume: 70, Issue:2
Structures of steroidal alkaloid oligoglycosides, robeneosides A and B, and antidiabetogenic constituents from the Brazilian medicinal plant Solanum lycocarpum.
AID444056Fraction escaping gut-wall elimination in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1636440Drug 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 NA2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
Development of a cell viability assay to assess drug metabolite structure-toxicity relationships.
AID467613Volume of distribution at steady state in human2009European 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.
AID1215120Binding affinity to Wistar rat brain lipid by TRANSIL assay2011Drug metabolism and disposition: the biological fate of chemicals, Feb, Volume: 39, Issue:2
Brain tissue binding of drugs: evaluation and validation of solid supported porcine brain membrane vesicles (TRANSIL) as a novel high-throughput method.
AID588213Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in non-rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID1474167Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status2016Drug 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.
AID699539Inhibition of human liver OATP1B1 expressed in HEK293 Flp-In cells assessed as reduction in E17-betaG uptake at 20 uM by scintillation counting2012Journal 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.
AID311524Oral bioavailability in human2007Bioorganic & medicinal chemistry, Dec-15, Volume: 15, Issue:24
Hologram QSAR model for the prediction of human oral bioavailability.
AID625285Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic necrosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625286Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID598879Inhibition of rat Oat1 expressed in Xenopus oocytes2011Bioorganic & medicinal chemistry, Jun-01, Volume: 19, Issue:11
Elucidation of common pharmacophores from analysis of targeted metabolites transported by the multispecific drug transporter-Organic anion transporter1 (Oat1).
AID1589438Antidiabetic activity in mouse MIN6 cells after 83 passages assessed as increase in insulin secretion incubated for 48 hrs presence of 1 mM glucose by ELISA2019European journal of medicinal chemistry, Apr-15, Volume: 168Synthesis of new arylsulfonylspiroimidazolidine-2',4'-diones and study of their effect on stimulation of insulin release from MIN6 cell line, inhibition of human aldose reductase, sorbitol accumulations in various tissues and oxidative stress.
AID1311581Drug uptake in mouse hepatocytes measured at 120 secs relative to control2016Bioorganic & medicinal chemistry letters, 08-01, Volume: 26, Issue:15
Synthesis and evaluation of a series of 4-azaindole-containing p21-activated kinase-1 inhibitors.
AID1211798Intrinsic clearance in human using well stirred liver model by LC-MS/MS method2012Drug 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.
AID1589470Antihyperglycemic activity in alloxanized BALB/c mouse model of diabetes assessed as blood glucose level at 150 mg/kg, po measured at 0 hr (Rvb = 223.6 +/- 4.67)2019European journal of medicinal chemistry, Apr-15, Volume: 168Synthesis of new arylsulfonylspiroimidazolidine-2',4'-diones and study of their effect on stimulation of insulin release from MIN6 cell line, inhibition of human aldose reductase, sorbitol accumulations in various tissues and oxidative stress.
AID29359Ionization constant (pKa)2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID1124413Hypoglycemic activity in 48 hrs fasted Charles River rat at 200 mg/kg, po measured at 1 hr relative to control1979Journal of medicinal chemistry, Jul, Volume: 22, Issue:7
Synthesis and hypoglycemic activity of pyridyl alcohols.
AID625292Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) combined score2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID496828Antimicrobial activity against Leishmania donovani2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID702025Induction of nitrite production in rat INS-1E cells assessed per well at 200 uM after 2 hrs by Griess method in presence of 2 mM glucose2012Bioorganic & medicinal chemistry letters, Jun-01, Volume: 22, Issue:11
Synthesis and preliminary biological profile of new NO-donor tolbutamide analogues.
AID1589475Antihyperglycemic activity in alloxanized BALB/c mouse assessed as reduction in blood glucose level at 150 mg/kg, po measured after 8 hrs relative to control2019European journal of medicinal chemistry, Apr-15, Volume: 168Synthesis of new arylsulfonylspiroimidazolidine-2',4'-diones and study of their effect on stimulation of insulin release from MIN6 cell line, inhibition of human aldose reductase, sorbitol accumulations in various tissues and oxidative stress.
AID496826Antimicrobial activity against Entamoeba histolytica2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1079941Liver damage due to vascular disease: peliosis hepatitis, hepatic veno-occlusive disease, Budd-Chiari syndrome. Value is number of references indexed. [column 'VASC' in source]
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID327170Binding affinity to human serum albumin by PAMPA method2008Journal of medicinal chemistry, Apr-10, Volume: 51, Issue:7
New approach to measure protein binding based on a parallel artificial membrane assay and human serum albumin.
AID1211796Intrinsic clearance in cryopreserved human HepaRG cells assessed per 10'6 cells by LC-MS/MS method2012Drug 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.
AID179736In vitro inhibition of glucose oxidation by the compound in isolated rat fat cells1983Journal of medicinal chemistry, Jul, Volume: 26, Issue:7
Sulfonyliminoimidazolidines. A new class of oral hypoglycemic agents. 2. Mode of action and X-ray structure of 1-[[p-[2-(crotonylamino)ethyl]phenyl]sulfonyl]-3-cyclohexyl-2-iminoimidazolidine.
AID625291Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver function tests abnormal2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID132162Hypoglycemic activity causing more than a 20% blood glucose decrease in fasting mice1989Journal of medicinal chemistry, Jul, Volume: 32, Issue:7
N-(cyclohexylcarbonyl)-D-phenylalanines and related compounds. A new class of oral hypoglycemic agents. 2.
AID27167Delta logD (logD6.5 - logD7.4)2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID1135170Hypoglycemic activity in 48 hrs fasted rat assessed as reduction in glucose level at 200 mg/kg, po measured after 1 hr1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Synthesis and hypoglycemic activity of S-acyl derivatives of 3-mercaptopicolinic acid.
AID625281Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholelithiasis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID166786In vitro insulin release was stimulated by the compound at a concentration of 0.9 mmol/L in rabbit pancreas1983Journal of medicinal chemistry, Jul, Volume: 26, Issue:7
Sulfonyliminoimidazolidines. A new class of oral hypoglycemic agents. 2. Mode of action and X-ray structure of 1-[[p-[2-(crotonylamino)ethyl]phenyl]sulfonyl]-3-cyclohexyl-2-iminoimidazolidine.
AID1473740Inhibition 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 assay2013Toxicological 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.
AID681848TP_TRANSPORTER: inhibition of Digoxin uptake (Digoxin: 0.05 uM, Tolbutamide: 1000 uM) in Oatp2-expressing LLC-PK1 cells2002Pharmaceutical research, Feb, Volume: 19, Issue:2
Comparative inhibitory effects of different compounds on rat oatpl (slc21a1)- and Oatp2 (Slc21a5)-mediated transport.
AID444057Fraction escaping hepatic elimination in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID1079938Chronic 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]
AID444051Total clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID239780Percentage plasma protein binding towards human serum albumin2005Journal of medicinal chemistry, Apr-07, Volume: 48, Issue:7
Predicting human serum albumin affinity of interleukin-8 (CXCL8) inhibitors by 3D-QSPR approach.
AID603953In-vivo plasma to lung partition coefficients of the compound, logP(lung) in rat2008European 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.
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID1211791Fraction unbound in human hepatocytes2012Drug 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.
AID1443980Inhibition 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]-tauroch2010Toxicological 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.
AID604742Displacement of radiolabeled dansylsarcosine from fatty acid-free human serum albumin site 2 in phosphate buffer at pH 7.4 at 12 uM by fluorescence spectroscopy2010Bioorganic & medicinal chemistry, Nov-01, Volume: 18, Issue:21
A combined spectroscopic and crystallographic approach to probing drug-human serum albumin interactions.
AID1449628Inhibition of human BSEP expressed in baculovirus transfected fall armyworm Sf21 cell membranes vesicles assessed as reduction in ATP-dependent [3H]-taurocholate transport into vesicles incubated for 5 mins by Topcount based rapid filtration method2012Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 40, Issue:12
Mitigating the inhibition of human bile salt export pump by drugs: opportunities provided by physicochemical property modulation, in silico modeling, and structural modification.
AID699541Inhibition 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 counting2012Journal 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.
AID625290Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver fatty2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1636357Drug 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 NA2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
Development of a cell viability assay to assess drug metabolite structure-toxicity relationships.
AID409956Inhibition of mouse brain MAOB2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AID977599Inhibition of sodium fluorescein uptake in OATP1B1-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM2013Molecular pharmacology, Jun, Volume: 83, Issue:6
Structure-based identification of OATP1B1/3 inhibitors.
AID678874TP_TRANSPORTER: inhibition of Gly-Sar uptake (Gly-Sar: 20 uM, Tolbutamide: 1000uM) in PEPT2-expressing LLC-PK1 cells2000European journal of pharmacology, Mar-24, Volume: 392, Issue:1-2
Inhibitory effect of novel oral hypoglycemic agent nateglinide (AY4166) on peptide transporters PEPT1 and PEPT2.
AID679148TP_TRANSPORTER: inhibition of PAH uptake in Xenopus laevis oocytes2000European journal of pharmacology, Jun-16, Volume: 398, Issue:2
Inhibitory effect of anti-diabetic agents on rat organic anion transporter rOAT1.
AID1474166Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index2016Drug 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.
AID1215123Binding affinity to Wistar rat serum albumin2011Drug metabolism and disposition: the biological fate of chemicals, Feb, Volume: 39, Issue:2
Brain tissue binding of drugs: evaluation and validation of solid supported porcine brain membrane vesicles (TRANSIL) as a novel high-throughput method.
AID625279Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for bilirubinemia2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID7273Antitumor activity in vivo against the 6C3HED lymphosarcoma dosed for 10 days at 600 mg/kg1990Journal of medicinal chemistry, Sep, Volume: 33, Issue:9
Novel agents effective against solid tumors: the diarylsulfonylureas. Synthesis, activities, and analysis of quantitative structure-activity relationships.
AID1589472Antihyperglycemic activity in alloxanized BALB/c mouse model of diabetes assessed as blood glucose level at 150 mg/kg, po measured after 4 hrs (Rvb = 206 +/- 4.89)2019European journal of medicinal chemistry, Apr-15, Volume: 168Synthesis of new arylsulfonylspiroimidazolidine-2',4'-diones and study of their effect on stimulation of insulin release from MIN6 cell line, inhibition of human aldose reductase, sorbitol accumulations in various tissues and oxidative stress.
AID1589437Antidiabetic activity in mouse MIN6 cells after 35 passages assessed as increase in insulin secretion incubated for 48 hrs presence of 25 mM glucose by ELISA2019European journal of medicinal chemistry, Apr-15, Volume: 168Synthesis of new arylsulfonylspiroimidazolidine-2',4'-diones and study of their effect on stimulation of insulin release from MIN6 cell line, inhibition of human aldose reductase, sorbitol accumulations in various tissues and oxidative stress.
AID1145018Hypoglycemic activity in fasted glucose primed Sprague-Dawley rat assessed as plasma glucose level at 100 mg/kg administered via oral gavage measured after 2 hrs by glucose-oxidase method relative to control1976Journal of medicinal chemistry, Mar, Volume: 19, Issue:3
Hypoglycemic alpha-cycloalkylphenylmehtyl, furanalkyl, and thiophenealkyl lactamimides.
AID496819Antimicrobial activity against Plasmodium falciparum2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID1862574Inhibition of CYP2C9 (unknown origin)
AID1211792Hepatic clearance in human2012Drug 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.
AID166778In vitro insulin release was stimulated by the compound at a concentration of 0.003 mmol/L in rabbit pancreas1983Journal of medicinal chemistry, Jul, Volume: 26, Issue:7
Sulfonyliminoimidazolidines. A new class of oral hypoglycemic agents. 2. Mode of action and X-ray structure of 1-[[p-[2-(crotonylamino)ethyl]phenyl]sulfonyl]-3-cyclohexyl-2-iminoimidazolidine.
AID277370Inhibition of increase in serum glucose level in sucrose-loaded Wistar rat at 25 mg/kg, po after 1 hr2007Journal of natural products, Feb, Volume: 70, Issue:2
Structures of steroidal alkaloid oligoglycosides, robeneosides A and B, and antidiabetogenic constituents from the Brazilian medicinal plant Solanum lycocarpum.
AID702029Induction of glucose-stimulated insulin release from rat INS-1E cells at 200 uM after 1 hr by coated charcoal immunoassay in presence of 2 mM glucose2012Bioorganic & medicinal chemistry letters, Jun-01, Volume: 22, Issue:11
Synthesis and preliminary biological profile of new NO-donor tolbutamide analogues.
AID977602Inhibition of sodium fluorescein uptake in OATP1B3-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM2013Molecular pharmacology, Jun, Volume: 83, Issue:6
Structure-based identification of OATP1B1/3 inhibitors.
AID301107Insulinotropic activity in rat RIN5F cells assessed as insulin secretion per ug of total protein at 10 uM2007Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21
Synthesis and antidiabetic activity of 2,5-disubstituted-3-imidazol-2-yl-pyrrolo[2,3-b]pyridines and thieno[2,3-b]pyridines.
AID91481Binding constant against human serum albumin (HSA)2001Journal of medicinal chemistry, Dec-06, Volume: 44, Issue:25
Cheminformatic models to predict binding affinities to human serum albumin.
AID301099Insulinotropic activity in rat RIN5F cells assessed as glucose dependent insulin secretion per ug of total protein at 1 uM2007Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21
Synthesis and antidiabetic activity of 2,5-disubstituted-3-imidazol-2-yl-pyrrolo[2,3-b]pyridines and thieno[2,3-b]pyridines.
AID399329Hypoglycemic activity in glucose-fed rabbit assessed as reduction of plasma glucose at 50 mg/kg, po after 1.5 hrs
AID1209457Unbound Cmax in human plasma2012Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 40, Issue:1
In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans.
AID1145021Hypoglycemic activity in fasted glucose primed Sprague-Dawley rat assessed as plasma glucose level at 12.5 mg/kg administered via oral gavage measured after 2 hrs by glucose-oxidase method relative to control1976Journal of medicinal chemistry, Mar, Volume: 19, Issue:3
Hypoglycemic alpha-cycloalkylphenylmehtyl, furanalkyl, and thiophenealkyl lactamimides.
AID1079933Acute 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
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID1145020Hypoglycemic activity in fasted glucose primed Sprague-Dawley rat assessed as plasma glucose level at 25 mg/kg administered via oral gavage measured after 2 hrs by glucose-oxidase method relative to control1976Journal of medicinal chemistry, Mar, Volume: 19, Issue:3
Hypoglycemic alpha-cycloalkylphenylmehtyl, furanalkyl, and thiophenealkyl lactamimides.
AID1589439Antidiabetic activity in mouse MIN6 cells after 83 passages assessed as increase in insulin secretion incubated for 48 hrs presence of 25 mM glucose by ELISA2019European journal of medicinal chemistry, Apr-15, Volume: 168Synthesis of new arylsulfonylspiroimidazolidine-2',4'-diones and study of their effect on stimulation of insulin release from MIN6 cell line, inhibition of human aldose reductase, sorbitol accumulations in various tissues and oxidative stress.
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID277373Inhibition of increase in serum glucose level in sucrose-loaded Wistar rat at 25 mg/kg, po after 2 hrs2007Journal of natural products, Feb, Volume: 70, Issue:2
Structures of steroidal alkaloid oligoglycosides, robeneosides A and B, and antidiabetogenic constituents from the Brazilian medicinal plant Solanum lycocarpum.
AID1473738Inhibition 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 assay2013Toxicological 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.
AID1124415Hypoglycemic activity in 48 hrs fasted Charles River rat at 200 mg/kg, po measured at 4 hrs relative to control1979Journal of medicinal chemistry, Jul, Volume: 22, Issue:7
Synthesis and hypoglycemic activity of pyridyl alcohols.
AID301098Insulinotropic activity in rat RIN5F cells assessed as glucose dependent insulin secretion per ug of total protein at 0.1 uM2007Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21
Synthesis and antidiabetic activity of 2,5-disubstituted-3-imidazol-2-yl-pyrrolo[2,3-b]pyridines and thieno[2,3-b]pyridines.
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID702030Induction of glucose-stimulated insulin release from rat INS-1E cells at 200 uM after 1 hr by coated charcoal immunoassay in presence of 2 mM glucose relative to control2012Bioorganic & medicinal chemistry letters, Jun-01, Volume: 22, Issue:11
Synthesis and preliminary biological profile of new NO-donor tolbutamide analogues.
AID399328Hypoglycemic activity in glucose-fed rabbit assessed as reduction of plasma glucose at 50 mg/kg, po after 1 hr
AID1211797Intrinsic clearance in cryopreserved human hepatocytes cells assessed per 10'6 cells by LC-MS/MS method2012Drug 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.
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID496830Antimicrobial activity against Leishmania major2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID625288Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for jaundice2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1135172Hypoglycemic activity in 48 hrs fasted rat assessed as reduction in glucose level at 200 mg/kg, po measured after 4 hrs1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Synthesis and hypoglycemic activity of S-acyl derivatives of 3-mercaptopicolinic acid.
AID444052Hepatic clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1473739Inhibition 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 assay2013Toxicological 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.
AID399331Hypoglycemic activity in glucose-fed rabbit assessed as reduction of plasma glucose at 50 mg/kg, po after 2.5 hrs
AID399330Hypoglycemic activity in glucose-fed rabbit assessed as reduction of plasma glucose at 50 mg/kg, po after 2 hrs
AID444054Oral bioavailability in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1133997Hypoglycemic activity in 48-hrs fasted rat assessed as decrease in blood glucose level at 200 mg/kg, po after 4 hrs1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Mercapto heterocyclic carboxylic acids, analogues of 3-mercaptopicolinic acid.
AID176488Compound evaluated for hypoglycemic activity by lowering blood glucose in normal rats by 50% after oral administration1983Journal of medicinal chemistry, Jul, Volume: 26, Issue:7
Sulfonyliminoimidazolidines. A new class of oral hypoglycemic agents. 1. 1-[[p-[2-(acylamino)ethyl]phenyl]sulfonyl]-2-iminoimidazolidines.
AID453204Permeability in human skin after 48 hrs by Franz cell permeability assay2010Bioorganic & 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.
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID197696In vivo increase of plasma insulin in normal rats at a hypoglycemic dose of 0.17 mmol/kg.1983Journal of medicinal chemistry, Jul, Volume: 26, Issue:7
Sulfonyliminoimidazolidines. A new class of oral hypoglycemic agents. 2. Mode of action and X-ray structure of 1-[[p-[2-(crotonylamino)ethyl]phenyl]sulfonyl]-3-cyclohexyl-2-iminoimidazolidine.
AID604741Displacement of radiolabeled warfarin from fatty acid-free human serum albumin site 1 in phosphate buffer at pH 7.4 at 12 uM by fluorescence spectroscopy2010Bioorganic & medicinal chemistry, Nov-01, Volume: 18, Issue:21
A combined spectroscopic and crystallographic approach to probing drug-human serum albumin interactions.
AID1589474Antihyperglycemic activity in alloxanized BALB/c mouse model of diabetes assessed as blood glucose level at 150 mg/kg, po measured after 8 hrs (Rvb = 218 +/- 4.10)2019European journal of medicinal chemistry, Apr-15, Volume: 168Synthesis of new arylsulfonylspiroimidazolidine-2',4'-diones and study of their effect on stimulation of insulin release from MIN6 cell line, inhibition of human aldose reductase, sorbitol accumulations in various tissues and oxidative stress.
AID173789Compound evaluated for hypoglycemic activity by lowering blood glucose in normal rats by 20% after oral administration1983Journal of medicinal chemistry, Jul, Volume: 26, Issue:7
Sulfonyliminoimidazolidines. A new class of oral hypoglycemic agents. 1. 1-[[p-[2-(acylamino)ethyl]phenyl]sulfonyl]-2-iminoimidazolidines.
AID301105Insulinotropic activity in rat RIN5F cells assessed as insulin secretion per ug of total protein at 0.1 uM2007Bioorganic & medicinal chemistry, Nov-01, Volume: 15, Issue:21
Synthesis and antidiabetic activity of 2,5-disubstituted-3-imidazol-2-yl-pyrrolo[2,3-b]pyridines and thieno[2,3-b]pyridines.
AID540209Volume of distribution at steady state in human after iv administration2008Drug 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.
AID588212Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID679856TP_TRANSPORTER: inhibition of Gly-Sar uptake (Gly-Sar: 20 uM, Tolbutamide: 1000uM) in PEPT1-expressing LLC-PK1 cells2000European journal of pharmacology, Mar-24, Volume: 392, Issue:1-2
Inhibitory effect of novel oral hypoglycemic agent nateglinide (AY4166) on peptide transporters PEPT1 and PEPT2.
AID277367Inhibition of increase in serum glucose level in sucrose-loaded Wistar rat at 25 mg/kg, po after 0.5 hrs2007Journal of natural products, Feb, Volume: 70, Issue:2
Structures of steroidal alkaloid oligoglycosides, robeneosides A and B, and antidiabetogenic constituents from the Brazilian medicinal plant Solanum lycocarpum.
AID300391Effect on glucose-dependent insulin secretion activity per ug of total protein in rat RIN5F cells at 0.1 uM after 30 mins2007Bioorganic & medicinal chemistry, Sep-01, Volume: 15, Issue:17
Synthesis of 3,8,9-trisubstituted-1,7,9-triaza-fluorene-6-carboxylic acid derivatives as a new class of insulin secretagogues.
AID588210Human drug-induced liver injury (DILI) modelling dataset from Ekins et al2010Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 38, Issue:12
A predictive ligand-based Bayesian model for human drug-induced liver injury.
AID567091Drug absorption in human assessed as human intestinal absorption rate2011European journal of medicinal chemistry, Jan, Volume: 46, Issue:1
Prediction of drug intestinal absorption by new linear and non-linear QSPR.
AID540212Mean residence time in human after iv administration2008Drug 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.
AID625284Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic failure2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID277378Inhibition of increase in serum glucose level in sucrose-loaded Wistar rat at 12.5 mg/kg, po after 2 hrs2007Journal of natural products, Feb, Volume: 70, Issue:2
Structures of steroidal alkaloid oligoglycosides, robeneosides A and B, and antidiabetogenic constituents from the Brazilian medicinal plant Solanum lycocarpum.
AID402224Hypoglycemic activity in 16 hrs fasted Wistar rat assessed as reduction in serum glucose level at 100 mg/kg, po measured after 90 mins of glucose challenge by oral glucose tolerance test2004Journal of natural products, May, Volume: 67, Issue:5
Hypoglycemic effect and antioxidant potential of kaempferol-3,7-O-(alpha)-dirhamnoside from Bauhinia forficata leaves.
AID130089Hypoglycemic activity at the lowest dose that causing 20% blood glucose decrease (fasting mice, po)1988Journal of medicinal chemistry, Nov, Volume: 31, Issue:11
N-acylphenylalanines and related compounds. A new class of oral hypoglycemic agents.
AID425653Renal clearance in human2009Journal of medicinal chemistry, Aug-13, Volume: 52, Issue:15
Physicochemical determinants of human renal clearance.
AID625289Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver disease2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1589434Antidiabetic activity in mouse MIN6 cells after 35 passages assessed as increase in insulin secretion at 100 uM in presence of 25 mM glucose by ELISA relative to control2019European journal of medicinal chemistry, Apr-15, Volume: 168Synthesis of new arylsulfonylspiroimidazolidine-2',4'-diones and study of their effect on stimulation of insulin release from MIN6 cell line, inhibition of human aldose reductase, sorbitol accumulations in various tissues and oxidative stress.
AID467612Fraction unbound in human plasma2009European 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.
AID625283Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for elevated liver function tests2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID604743Displacement of radiolabeled warfarin from fatty acid containing human serum albumin site 1 in phosphate buffer at pH 7.4 at 12 uM by fluorescence spectroscopy2010Bioorganic & medicinal chemistry, Nov-01, Volume: 18, Issue:21
A combined spectroscopic and crystallographic approach to probing drug-human serum albumin interactions.
AID682107TP_TRANSPORTER: inhibition of E217betaG uptake (E217betaG: 0.1 uM, Tolbutamide: 1000 uM) in Oatp1-expressing LLC-PK1 cells2002Pharmaceutical research, Feb, Volume: 19, Issue:2
Comparative inhibitory effects of different compounds on rat oatpl (slc21a1)- and Oatp2 (Slc21a5)-mediated transport.
AID402156Hypoglycemic activity in diabetic KK-Ay mouse at 50 mg/kg, ip assessed as blood glucose level per 100 mL blood after 4 hrs1997Journal of natural products, Jun, Volume: 60, Issue:6
Hypoglycemic activity of some triterpenoid glycosides.
AID496817Antimicrobial activity against Trypanosoma cruzi2010Bioorganic & medicinal chemistry, Mar-15, Volume: 18, Issue:6
Multi-target spectral moment QSAR versus ANN for antiparasitic drugs against different parasite species.
AID702027Antiaggregatory activity in human platelet-rich plasma assessed as inhibition of collagen-induced aggregation at 300 uM pretreated 10 mins before addition of stimulus measured after 10 mins2012Bioorganic & medicinal chemistry letters, Jun-01, Volume: 22, Issue:11
Synthesis and preliminary biological profile of new NO-donor tolbutamide analogues.
AID402150Hypoglycemic activity in normal ddY mouse at 50 mg/kg, ip assessed as blood glucose level per 100 mL blood after 4 hrs1997Journal of natural products, Jun, Volume: 60, Issue:6
Hypoglycemic activity of some triterpenoid glycosides.
AID1211795Dissociation constant, pKa of the compound2012Drug 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.
AID1133995Hypoglycemic activity in 48-hrs fasted rat assessed as decrease in blood glucose level at 200 mg/kg, po after 1 hr1977Journal of medicinal chemistry, Apr, Volume: 20, Issue:4
Mercapto heterocyclic carboxylic acids, analogues of 3-mercaptopicolinic acid.
AID540211Fraction unbound in human after iv administration2008Drug 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.
AID294991Insulinotropic activity in RIN5F cells assessed as stimulation of glucose-dependent insulin secretion per ug of protein at 1 uM2007Bioorganic & medicinal chemistry, May-01, Volume: 15, Issue:9
Design, synthesis, and biological evaluation of substituted-N-(thieno[2,3-b]pyridin-3-yl)-guanidines, N-(1H-pyrrolo[2,3-b]pyridin-3-yl)-guanidines, and N-(1H-indol-3-yl)-guanidines.
AID409954Inhibition of mouse brain MAOA2008Journal of medicinal chemistry, Nov-13, Volume: 51, Issue:21
Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.
AID425652Total body clearance in human2009Journal of medicinal chemistry, Aug-13, Volume: 52, Issue:15
Physicochemical determinants of human renal clearance.
AID1884502Inhibition of CYP2C9 in human liver microsomes incubated for 15 to 40 mins in presence of NADPH2022European journal of medicinal chemistry, Aug-05, Volume: 238Expansion of the S-CN-DABO scaffold to exploit the impact on inhibitory activities against the non-nucleoside HIV-1 reverse transcriptase.
AID588459High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, Validation compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588459High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, Validation compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588459High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, Validation compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588460High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, Validation Compound Set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588460High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, Validation Compound Set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588460High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, Validation Compound Set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588461High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, Validation compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588461High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, Validation compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588461High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, Validation compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID1347093qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347094qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347095qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347092qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347424RapidFire Mass Spectrometry qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)2019The Journal of biological chemistry, 11-15, Volume: 294, Issue:46
Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1347103qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347154Primary screen GU AMC qHTS for Zika virus inhibitors2020Proceedings 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.
AID1347104qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347108qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347098qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347096qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347097qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347407qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Pharmaceutical Collection2020ACS 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.
AID1347102qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347425Rhodamine-PBP qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)2019The Journal of biological chemistry, 11-15, Volume: 294, Issue:46
Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1745845Primary qHTS for Inhibitors of ATXN expression
AID1347100qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347101qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347106qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347091qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347105qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347099qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347107qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347090qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347089qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID504749qHTS profiling for inhibitors of Plasmodium falciparum proliferation2011Science (New York, N.Y.), Aug-05, Volume: 333, Issue:6043
Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal 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.
AID1802994UDP-glucuronosyltransferase Activity Assay from Article 10.3109/14756366.2010.518965: \\The inhibition study of human UDP-glucuronosyltransferases with cytochrome P450 selective substrates and inhibitors.\\2011Journal of enzyme inhibition and medicinal chemistry, Jun, Volume: 26, Issue:3
The inhibition study of human UDP-glucuronosyltransferases with cytochrome P450 selective substrates and inhibitors.
AID1802150TREK1 Assay from Article 10.1111/cbdd.12810: \\Identification of the first in silico-designed TREK1 antagonists that block channel currents dose dependently.\\2016Chemical biology & drug design, Dec, Volume: 88, Issue:6
Identification of the first in silico-designed TREK1 antagonists that block channel currents dose dependently.
AID1346573Mouse Kir6.2 (Inwardly rectifying potassium channels)1995Science (New York, N.Y.), Nov-17, Volume: 270, Issue:5239
Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.
AID1346630Rat Kir6.2 (Inwardly rectifying potassium channels)1996The Journal of biological chemistry, Oct-04, Volume: 271, Issue:40
A novel sulfonylurea receptor forms with BIR (Kir6.2) a smooth muscle type ATP-sensitive K+ channel.
AID1794808Fluorescence-based screening to identify small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase (Pf-apPOL).2014Journal of biomolecular screening, Jul, Volume: 19, Issue:6
A High-Throughput Assay to Identify Inhibitors of the Apicoplast DNA Polymerase from Plasmodium falciparum.
AID1794808Fluorescence-based screening to identify small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase (Pf-apPOL).
AID1224864HCS microscopy assay (F508del-CFTR)2016PloS one, , Volume: 11, Issue:10
Increasing the Endoplasmic Reticulum Pool of the F508del Allele of the Cystic Fibrosis Transmembrane Conductance Regulator Leads to Greater Folding Correction by Small Molecule Therapeutics.
AID1159550Human Phosphogluconate dehydrogenase (6PGD) Inhibitor Screening2015Nature cell biology, Nov, Volume: 17, Issue:11
6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1-AMPK signalling.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (5,018)

TimeframeStudies, This Drug (%)All Drugs %
pre-19903717 (74.07)18.7374
1990's578 (11.52)18.2507
2000's418 (8.33)29.6817
2010's258 (5.14)24.3611
2020's47 (0.94)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 60.41

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index60.41 (24.57)
Research Supply Index8.63 (2.92)
Research Growth Index4.19 (4.65)
Search Engine Demand Index107.85 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (60.41)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials238 (4.43%)5.53%
Reviews212 (3.95%)6.00%
Case Studies131 (2.44%)4.05%
Observational0 (0.00%)0.25%
Other4,787 (89.18%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (25)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Randomized Drug Interaction Study of RO4929097 for Advanced Solid Tumors [NCT01218620]Phase 117 participants (Actual)Interventional2010-09-30Completed
Licorice Botanical Dietary Supplements - Metabolism and Safety in Women [NCT03948243]Phase 119 participants (Actual)Interventional2019-04-01Completed
Incretin-based Drugs and the Risk of Heart Failure: A Multi-center Network Observational Study [NCT02456428]1,499,650 participants (Actual)Observational2014-03-31Completed
A Multi-center, Double-blind, Placebo-controlled, Randomized Study to Compare the Effect of a Subcutaneous Canakinumab Administration to Placebo in Patients With Impaired Glucose Tolerance or Patients With Type 2 Diabetes Treated With Differing Baseline D [NCT01068860]Phase 2246 participants (Actual)Interventional2010-02-28Completed
A Phase 1, Open-Label, Fixed-sequence, 5-part, Drug-drug Interaction Study of Tucatinib to Evaluate the Effects of CYP3A4 and CYP2C8 Inhibition and Induction on the Pharmacokinetics of Tucatinib and to Evaluate the Effects of Tucatinib on the Pharmacokine [NCT03723395]Phase 1116 participants (Actual)Interventional2018-09-17Completed
Effect of Acute Ethanol Consumption on The Activity of Major Cytochrome P450 Enzymes, NAT2 and P-glycoprotein [NCT02515526]16 participants (Actual)Interventional2015-06-30Completed
An Open-label, Fixed Sequence Phase I Study in Healthy Male Volunteers to Assess Sequentially the Effects of Multiple Doses of BI 207127 NA, BI 201335 NA Followed by the Combination of BI 207127 NA and BI 201335 NA, on the Single Dose Pharmacokinetics of [NCT02182401]Phase 137 participants (Actual)Interventional2009-07-31Terminated
The Use of Incretin-based Drugs and the Risk of Acute Pancreatitis in Patients With Type 2 Diabetes [NCT02476760]1,417,914 participants (Actual)Observational2014-03-31Completed
Effects of Type 2 Diabetes on CYP450s Activities; Intersubject Variability in Drug Metabolism. [NCT02291666]Phase 473 participants (Actual)Interventional2015-04-30Completed
A Single-centre, Open-label, Fixed-sequence Trial to Evaluate the Impact of C21 on the Exposure of CYP1A2, CYP2C9, CYP3A4 and P-gp Substrates in Healthy Volunteers [NCT05830799]Phase 118 participants (Actual)Interventional2023-03-29Completed
A Fixed-Sequence Trial to Examine the Effect of Multiple-Dose CT1812 Administration on Standard Probes of CYP2C19 (Omeprazole), CYP2C9 (Tolbutamide), CYP2D6 (Dextromethorphan), and CYP3A4/5 (Midazolam) Activity in Healthy Adult Volunteers [NCT03716427]Phase 116 participants (Actual)Interventional2016-11-10Completed
An Open-label, Single Sequence, Crossover Drug-drug Interaction Study Assessing the Effect of Pexidartinib on the Pharmacokinetics of CYP3A4 and CYP2C9 Substrates in Patients [NCT03291288]Phase 132 participants (Actual)Interventional2018-02-26Completed
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 136 participants (Actual)Interventional2017-03-28Completed
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 127 participants (Actual)Interventional2018-03-06Completed
A Phase I, Open Label, Multi Centre Study in Healthy Volunteers to Estimate the Effect of Multiple Doses of AZD2066 on the Activity of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 by Administering a Cocktail of Caffeine, Bupropion, Tolbutamide, Omep [NCT00930306]Phase 115 participants (Actual)Interventional2009-06-30Completed
Effects of Genotype on CYP2C9 Drug Interactions [NCT01061112]23 participants (Actual)Observational2009-12-31Completed
PHASE 1, OPEN-LABEL, FIXED-SEQUENCE, 2-PERIOD STUDY TO ESTIMATE THE EFFECT OF MULTIPLE-DOSE RITLECITINIB (PF-06651600) ON THE PHARMACOKINETICS OF SINGLE-DOSE TOLBUTAMIDE IN HEALTHY PARTICIPANTS [NCT05097716]Phase 112 participants (Actual)Interventional2021-11-02Completed
The Effect of Tasisulam on the CYP2C9-Mediated Metabolism of Tolbutamide: A Pharmacokinetic Interaction Study in Cancer Patients With Advanced and/or Metastatic Solid Tumors or Lymphoma [NCT01185548]Phase 14 participants (Actual)Interventional2010-07-31Terminated(stopped due to Terminated based on safety results from another trial)
Blockade of Vascular Potassium Channels During Human Endotoxemia [NCT00185003]Phase 136 participants (Actual)Interventional2003-01-31Completed
An Open-Label, Multiple-Dose, Non-Randomized Study to Assess the Drug-Drug Interactions of Proellex® (CDB-4124) With Cytochrome P450 Isoenzymes CYP1A2, 2C9, 2C19, 2D6, and 3A4 in Healthy Female Subjects [NCT00741468]Phase 118 participants (Actual)Interventional2008-07-31Completed
"An Open-Label, Fixed-Sequence Study in Healthy Male Subjects to Assess the Drug Interaction Potential of Multiple-Doses of JNJ-54861911 With a Drug Cocktail Representative for CYP3A4, CYP2B6, CYP2C9, and CYP1A2 Substrates" [NCT02211079]Phase 116 participants (Actual)Interventional2014-09-30Completed
A Multi-centre, Open Label, Parallel Group Trial to Evaluate the Pharmacokinetic Interactions Between BI 207127 (600 mg t.i.d. or 600 mg b.i.d.) and BI 201335 (120 mg q.d.) Given in Combination With Ribavirin for 24 Weeks, and Their Combined Effect on the [NCT01525628]Phase 172 participants (Actual)Interventional2012-04-30Completed
The Use of Incretin-based Drugs and the Risk of Pancreatic Cancer in Patients With Type 2 Diabetes [NCT02475499]886,172 participants (Actual)Observational2014-03-31Completed
A PHASE 1, OPEN-LABEL, CROSS-OVER, FIXED SEQUENCE STUDY TO EVALUATE THE EFFECT OF MULTIPLE DOSES OF DS-1971A ON THE SINGLE DOSE PHARMACOKINETICS OF PROBE SUBSTRATES FOR CYP2B6, CYP2C8, CYP2C9, CYP2C19 AND CYP3A4 ENZYMES IN HEALTHY MALE AND FEMALE SUBJECTS [NCT02473627]Phase 118 participants (Actual)Interventional2015-05-31Completed
The Effect of High Dose Rifampicin on the Activity of Cytochrome P450 Enzymes and P-glycoprotein in Patients With Pulmonary Tuberculosis: a Cocktail Phenotyping Study [NCT04525235]Phase 125 participants (Actual)Interventional2021-01-07Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00741468 (1) [back to overview]Plasma AUC Ratio of Day 1 and Day 8
NCT01068860 (16) [back to overview]Mean Change in Absolute Glucose Level at 2 Hours, From Baseline to 4 Weeks
NCT01068860 (16) [back to overview]Mean Change in C-peptide Area Under the Curve (AUC), 0-4 Hours, From Baseline to 4 Weeks
NCT01068860 (16) [back to overview]Mean Change in Fasting Plasma Glucose, From Baseline to 4 Weeks
NCT01068860 (16) [back to overview]Mean Change in Fasting Plasma Insulin, From Baseline to 4 Weeks
NCT01068860 (16) [back to overview]Mean Change in Fructosamine, From Baseline to 4 Weeks
NCT01068860 (16) [back to overview]Mean Change in Insulin Area Under the Curve (AUC) 0-4 Hours, From Baseline to 4 Weeks
NCT01068860 (16) [back to overview]Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 0-2 Hours, From Baseline to 4 Weeks.
NCT01068860 (16) [back to overview]Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 0-4 Hours, From Baseline to 4 Weeks.
NCT01068860 (16) [back to overview]Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 2-4 Hours, From Baseline to 4 Weeks
NCT01068860 (16) [back to overview]Mean Change in Peak Plasma C-peptide Level, From Baseline to 4 Weeks
NCT01068860 (16) [back to overview]Mean Change in Peak Plasma Glucose, From Baseline to 4 Weeks
NCT01068860 (16) [back to overview]Mean Change in Peak Plasma Insulin, From Baseline to 4 Weeks
NCT01068860 (16) [back to overview]Mean Change in Post-prandial Glucose Area Under the Curve (AUC)0-4 Hours, From Baseline to 4 Weeks
NCT01068860 (16) [back to overview]Mean Change in Quantitative Insulin Sensitivity Check Index (QUICKI) Score, From Baseline to 4 Weeks
NCT01068860 (16) [back to overview]Mean Change in Fasting Glucose Disposition Index(GDI)1 and Index 2, From Baseline to 4 Weeks
NCT01068860 (16) [back to overview]Number of Participants Reporting Death, Serious Adverse Events (SAEs) and Adverse Events (AEs) Above 5% Frequency, From Baseline to 4 Weeks
NCT01185548 (4) [back to overview]Pharmacokinetics of Tolbutamide, Staggered Dosing in Period 3, Area Under the Curve (AUC 0-∞)
NCT01185548 (4) [back to overview]Pharmacokinetics of Tolbutamide, Observed Time at Maximal Concentration (Tmax)
NCT01185548 (4) [back to overview]Pharmacokinetics of Tolbutamide, Maximum Concentration (Cmax)
NCT01185548 (4) [back to overview]Pharmacokinetics of Tolbutamide, Concurrent Dosing, Area Under the Curve (AUC 0-∞)
NCT01525628 (24) [back to overview]C6hr of Deleobuvir Reduction Metabolite CD 6168
NCT01525628 (24) [back to overview]Cmax of 1-OH-Midazolam (1-hydroxy-midazolam)
NCT01525628 (24) [back to overview]Cmax of Deleobuvir (BI 207127)
NCT01525628 (24) [back to overview]Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)
NCT01525628 (24) [back to overview]Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)
NCT01525628 (24) [back to overview]Cmax of Deleobuvir Reduction Metabolite CD 6168
NCT01525628 (24) [back to overview]Cmax of Faldaprevir (BI 201335)
NCT01525628 (24) [back to overview]Cmax of Midazolam
NCT01525628 (24) [back to overview]Number of Participants With Sustained Virological Response (SVR12)
NCT01525628 (24) [back to overview]Cmax of Tolbutamide
NCT01525628 (24) [back to overview]Cmax of Caffeine
NCT01525628 (24) [back to overview]Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours
NCT01525628 (24) [back to overview]AUC 0-6hr of Deleobuvir (BI 207127)
NCT01525628 (24) [back to overview]AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)
NCT01525628 (24) [back to overview]AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)
NCT01525628 (24) [back to overview]AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168
NCT01525628 (24) [back to overview]AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam)
NCT01525628 (24) [back to overview]AUC 0-infinity of Caffeine
NCT01525628 (24) [back to overview]AUC 0-infinity of Midazolam
NCT01525628 (24) [back to overview]AUC 0-infinity of Tolbutamide
NCT01525628 (24) [back to overview]C24hr of Faldaprevir (BI 201335)
NCT01525628 (24) [back to overview]C6hr of Deleobuvir (BI 207127)
NCT01525628 (24) [back to overview]C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)
NCT01525628 (24) [back to overview]C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam Metabolite, 1-Hydroxy Midazolam
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Tolbutamide
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam Metabolite, 1-Hydroxy Midazolam
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Tolbutamide
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Metabolite to Parent Ratio (MPR) for Midazolam
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Tolbutamide
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam Metabolite, 1-Hydroxy Midazolam
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Pexidartinib and ZAAD-1006a Metabolite
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Pexidartinib and ZAAD-1006a Metabolite
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Pexidartinib and ZAAD-1006a Metabolite
NCT03291288 (14) [back to overview]Overall Summary of Treatment-emergent Adverse Events
NCT05097716 (3) [back to overview]Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Tolbutamide Administered With and Without Ritlecitinib
NCT05097716 (3) [back to overview]Maximum Plasma Concentration (Cmax) of Tolbutamide Administered With and Without Ritlecitinib
NCT05097716 (3) [back to overview]Number of Participants With Treatment-Emergent Adverse Events (TEAEs) - All Causalities and Treatment Related

Plasma AUC Ratio of Day 1 and Day 8

"Assessment of the drug-drug interactions of Proellex® (CDB-4124) with cytochrome P450 isoenzymes CYP1A2, 2C9, 2C19, 2D6, and 3A4 in healthy female subjects administered 50 mg Proellex® once daily (QD). The Day 8 AUC was compared to the Day 1 AUC to determine inhibition.~For CYP1A2 the plasma paraxanthine/caffeine MR ratio (metabolic ratio) was used. For CYP2D6 the MR ratio of dextromethorphan/dextrorphan was used." (NCT00741468)
Timeframe: 8 days

InterventionRatio of geometric means Day 8 to Day 1 (Mean)
CYP1A21.093
CYP2C91.029
CYP2C191.104
CYP2D61.914
CYP3A42.245

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Mean Change in Absolute Glucose Level at 2 Hours, From Baseline to 4 Weeks

"Change in glucose level measured after 2 hours of fasting. Blood sample was drawn at 0 minutes and at 240 minutes.~A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population." (NCT01068860)
Timeframe: Baseline, 4 weeks

Interventionmmol/L (Least Squares Mean)
Canakinumab 150 mg + Metformin-0.53
Placebo + Metformin0.13
Canakinumab 150 mg + Metformin + Sulfonylurea-0.60
Placebo + Metformin + Sulfonylurea0.18
Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia-1.08
Placebo + Met + Sulfonyl + Thiaz-0.56
Canakinumab 150 mg + Insulin-0.56
Placebo + Insulin-0.16
Canakinumab 150 mg in Participants With IGT-0.26
Placebo in Participants With IGT-0.25

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Mean Change in C-peptide Area Under the Curve (AUC), 0-4 Hours, From Baseline to 4 Weeks

Blood samples were drawn after a test meal at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Insulin levels over 4 hrs were shown as Area Under the Curve,(AUC). AUC was calculated as: x=1 AUC ΣAx n Where Ax = AUC for the 240 min.interval, and X = 1 for the 1st interval. A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab vs placebo within each T2DM group. The mixed model didn't include the IGT group. (NCT01068860)
Timeframe: Baseline, 4 weeks

Interventionnmol*hour/L (Least Squares Mean)
Canakinumab 150 mg + Metformin-0.18
Placebo + Metformin-0.18
Canakinumab 150 mg + Metformin + Sulfonylurea-0.21
Placebo + Metformin + Sulfonylurea0.12
Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia-0.61
Placebo + Met + Sulfonyl + Thiaz0.02
Canakinumab 150 mg + Insulin0.16
Placebo + Insulin-0.29
Canakinumab 150 mg in Participants With IGT-0.43
Placebo in Participants With IGT-0.40

[back to top]

Mean Change in Fasting Plasma Glucose, From Baseline to 4 Weeks

"Change in Fasting Glucose Level measured from plasma taken at Baseline and after 4 weeks of treatment.~A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population" (NCT01068860)
Timeframe: Baseline, 4 weeks

Interventionmmol/L (Least Squares Mean)
Canakinumab 150 mg + Metformin-0.32
Placebo + Metformin0.33
Canakinumab 150 mg + Metformin + Sulfonylurea-0.20
Placebo + Metformin + Sulfonylurea-0.23
Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia-0.33
Placebo + Met + Sulfonyl + Thiaz-0.36
Canakinumab 150 mg + Insulin-0.26
Placebo + Insulin-0.80
Canakinumab 150 mg in Participants With IGT-0.06
Placebo in Participants With IGT0.10

[back to top]

Mean Change in Fasting Plasma Insulin, From Baseline to 4 Weeks

"Change in Fasting Insulin level taken from plasma, measured at Baseline and after 4 weeks of treatment.~A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population" (NCT01068860)
Timeframe: Baseline, 4 weeks

Interventionpmol/L (Least Squares Mean)
Canakinumab 150 mg + Metformin-3.58
Placebo + Metformin10.73
Canakinumab 150 mg + Metformin + Sulfonylurea-16.07
Placebo + Metformin + Sulfonylurea-9.40
Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia-0.77
Placebo + Met + Sulfonyl + Thiaz2.31
Canakinumab 150 mg + Insulin21.27
Placebo + Insulin25.67
Canakinumab 150 mg in Participants With IGT-.021
Placebo in Participants With IGT-3.43

[back to top]

Mean Change in Fructosamine, From Baseline to 4 Weeks

"Change in Fructosamine Level taken from plasma, measured at Baseline and after 4 weeks of treatment.~A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population" (NCT01068860)
Timeframe: Baseline, 4 weeks

Interventionmmol/L (Least Squares Mean)
Canakinumab 150 mg + Metformin-5.30
Placebo + Metformin-0.75
Canakinumab 150 mg + Metformin + Sulfonylurea-3.45
Placebo + Metformin + Sulfonylurea-7.50
Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia-1.81
Placebo + Met + Sulfonyl + Thiaz-3.07
Canakinumab 150 mg + Insulin-3.00
Placebo + Insulin-19.73
Canakinumab 150 mg in Participants With IGT-6.36
Placebo in Participants With IGT1.39

[back to top]

Mean Change in Insulin Area Under the Curve (AUC) 0-4 Hours, From Baseline to 4 Weeks

Blood samples were drawn after a test meal at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Insulin levels over 4 hrs were shown as Area Under the Curve,(AUC). AUC was calculated as: x=1 AUC ΣAx n Where Ax = AUC for the 240 min.interval, and X = 1 for the 1st interval. A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab vs placebo within each T2DM group. The mixed model didn't include the IGT group. (NCT01068860)
Timeframe: Baseline, 4 weeks

Interventionpmol*hour/L (Least Squares Mean)
Canakinumab 150 mg + Metformin-9.37
Placebo + Metformin1.21
Canakinumab 150 mg + Metformin + Sulfonylurea-73.25
Placebo + Metformin + Sulfonylurea-38.32
Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia-36.96
Placebo + Met + Sulfonyl + Thiaz8.46
Canakinumab 150 mg + Insulin163.87
Placebo + Insulin139.24
Canakinumab 150 mg in Participants With IGT44.27
Placebo in Participants With IGT-106.68

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Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 0-2 Hours, From Baseline to 4 Weeks.

Change in Insulin Secretion Rate stimulated by Liquid mixed-meal challenge. Blood samples were taken prior to and after meal for glucose and insulin at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes relative to the start of the meal.A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include patients from the IGT population (NCT01068860)
Timeframe: Baseline, 4 weeks

Interventionpmol/min/m^2/mmol/L (Least Squares Mean)
Canakinumab 150 mg + Metformin-0.06
Placebo + Metformin-0.23
Canakinumab 150 mg + Metformin + Sulfonylurea0.04
Placebo + Metformin + Sulfonylurea0.45
Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia-0.79
Placebo + Met + Sulfonyl + Thiaz1.16
Canakinumab 150 mg + Insulin1.23
Placebo + Insulin-0.49
Canakinumab 150 mg in Participants With IGT-1.50
Placebo in Participants With IGT-1.93

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Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 0-4 Hours, From Baseline to 4 Weeks.

Change in Insulin Secretion Rate stimulated by Liquid mixed-meal challenge. Blood samples were taken prior to and after meal for glucose, insulin and C-peptide at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes relative to the start of the meal. A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population. (NCT01068860)
Timeframe: Baseline, 4 weeks

Interventionpmol/min/m^2/mmol/L (Least Squares Mean)
Canakinumab 150 mg + Metformin0.44
Placebo + Metformin-0.99
Canakinumab 150 mg + Metformin + Sulfonylurea-0.32
Placebo + Metformin + Sulfonylurea1.22
Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia-0.63
Placebo + Met + Sulfonyl + Thiaz1.24
Canakinumab 150 mg + Insulin0.53
Placebo + Insulin-0.49
Canakinumab 150 mg in Participants With IGT-1.38
Placebo in Participants With IGT-1.35

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Mean Change in Meal Stimulated Insulin Secretion Rate (ISR) Relative to Glucose 2-4 Hours, From Baseline to 4 Weeks

Change in Insulin Secretion Rate stimulated by Liquid mixed-meal challenge Blood samples were taken prior to and after meal for glucose and insulin at sample times: -20, -10, -1 and 10, 20, 30, 60, 90, 120, 180, and 240 minutes relative to the start of the meal. A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population (NCT01068860)
Timeframe: Baseline, 4 weeks

Interventionpmol/min/m^2/mmol/L (Least Squares Mean)
Canakinumab 150 mg + Metformin0.21
Placebo + Metformin-2.15
Canakinumab 150 mg + Metformin + Sulfonylurea-2.98
Placebo + Metformin + Sulfonylurea2.02
Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia0.15
Placebo + Met + Sulfonyl + Thiaz1.19
Canakinumab 150 mg + Insulin-0.43
Placebo + Insulin-0.51
Canakinumab 150 mg in Participants With IGT-0.71
Placebo in Participants With IGT-1.00

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Mean Change in Peak Plasma C-peptide Level, From Baseline to 4 Weeks

"Change in mean peak plasma C-peptide level measured from Baseline to 4 weeks of treatment.~A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population." (NCT01068860)
Timeframe: Baseline, 4 weeks

Interventionnmol/L (Least Squares Mean)
Canakinumab 150 mg + Metformin-0.04
Placebo + Metformin-0.04
Canakinumab 150 mg + Metformin + Sulfonylurea-0.10
Placebo + Metformin + Sulfonylurea0.16
Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia-0.21
Placebo + Met + Sulfonyl + Thiaz0.05
Canakinumab 150 mg + Insulin0.07
Placebo + Insulin-0.14
Canakinumab 150 mg in Participants With IGT-0.18
Placebo in Participants With IGT-0.18

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Mean Change in Peak Plasma Glucose, From Baseline to 4 Weeks

"Change in peak plasma glucose level as measured from Baseline to 4 weeks of treatment.~A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population." (NCT01068860)
Timeframe: Baseline, 4 weeks

Interventionmmol/L (Least Squares Mean)
Canakinumab 150 mg + Metformin-0.41
Placebo + Metformin0.21
Canakinumab 150 mg + Metformin + Sulfonylurea-0.43
Placebo + Metformin + Sulfonylurea-0.03
Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia-0.82
Placebo + Met + Sulfonyl + Thiaz-0.77
Canakinumab 150 mg + Insulin-0.15
Placebo + Insulin-0.60
Canakinumab 150 mg in Participants With IGT-0.34
Placebo in Participants With IGT-0.04

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Mean Change in Peak Plasma Insulin, From Baseline to 4 Weeks

Change in mean peak plasma Insulin level as measured from Baseline to 4 weeks of treatment. A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population. (NCT01068860)
Timeframe: Baseline, 4 weeks

Interventionpmol/L (Least Squares Mean)
Canakinumab 150 mg + Metformin8.09
Placebo + Metformin44.56
Canakinumab 150 mg + Metformin + Sulfonylurea-55.07
Placebo + Metformin + Sulfonylurea11.33
Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia5.13
Placebo + Met + Sulfonyl + Thiaz-5.15
Canakinumab 150 mg + Insulin91.74
Placebo + Insulin36.87
Canakinumab 150 mg in Participants With IGT56.21
Placebo in Participants With IGT-26.43

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Mean Change in Post-prandial Glucose Area Under the Curve (AUC)0-4 Hours, From Baseline to 4 Weeks

Blood samples were drawn after a test meal at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min. Insulin levels over 4 hrs were shown as Area Under the Curve,(AUC). AUC was calculated as: x=1 AUC ΣAx n Where Ax = AUC for the 240 min.interval, and X = 1 for the 1st interval. A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab vs placebo within each T2DM group. The mixed model didn't include the IGT group. (NCT01068860)
Timeframe: Baseline, 4 weeks

Interventionmmol*hr/L (Least Squares Mean)
Canakinumab 150 mg + Metformin-0.59
Placebo + Metformin0.46
Canakinumab 150 mg + Metformin + Sulfonylurea-1.37
Placebo + Metformin + Sulfonylurea-1.24
Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia-3.58
Placebo + Met + Sulfonyl + Thiaz-2.88
Canakinumab 150 mg + Insulin-1.49
Placebo + Insulin-1.76
Canakinumab 150 mg in Participants With IGT-0.71
Placebo in Participants With IGT-0.10

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Mean Change in Quantitative Insulin Sensitivity Check Index (QUICKI) Score, From Baseline to 4 Weeks

"The Quantitative Insulin Sensitivity Check Index (QUICKI) score, measures insulin sensitivity which is the inverse of insulin resistance. The score is calculated by the equation: 1 /(log(fasting insulin µU/mL) + log(fasting glucose mg/dL)). In normal subjects the mean score ± SE is 0.366 ± 0.029.~A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT population." (NCT01068860)
Timeframe: Baseline, 4 weeks

Interventionnumber (Least Squares Mean)
Canakinumab 150 mg + Metformin0.004
Placebo + Metformin-0.000
Canakinumab 150 mg + Metformin + Sulfonylurea0.002
Placebo + Metformin + Sulfonylurea0.009
Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia0.018
Placebo + Met + Sulfonyl + Thiaz-0.001
Canakinumab 150 mg + Insulin-0.003
Placebo + Insulin0.005
Canakinumab 150 mg in Participants With IGT-0.001
Placebo in Participants With IGT0.001

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Mean Change in Fasting Glucose Disposition Index(GDI)1 and Index 2, From Baseline to 4 Weeks

GDI 1 is the product of insulin sensitivity index (Si)during the 1st phase of insulin secretion and β-cell function as measured by the acute insulin response (AIR).GDI 2 is the product of (Si)during the 2nd phase of insulin secretion and β-cell function as measured by the acute insulin response (AIR). A mixed model with treatment fitted as fixed effect, and population and the interaction of population and treatment fitted as random effects were used for the comparison of Canakinumab versus placebo within each T2DM population. The mixed model did not include participants from the IGT group. (NCT01068860)
Timeframe: Baseline, 4 weeks

,,,,,,,,,
Interventionnumber (Least Squares Mean)
Index 1Index 2 (n= 32,15, 29,15, 30,13, 25, 15, 20, 26)
Canakinumab 150 mg + Insulin0.25-0.21
Canakinumab 150 mg + Metformin0.060.14
Canakinumab 150 mg + Metformin + Sulfonylurea0.06-0.94
Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia0.240.62
Canakinumab 150 mg in Participants With IGT-0.51-0.16
Placebo + Insulin-0.27-0.25
Placebo + Met + Sulfonyl + Thiaz0.330.49
Placebo + Metformin-0.29-0.81
Placebo + Metformin + Sulfonylurea0.370.81
Placebo in Participants With IGT-0.64-0.31

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Number of Participants Reporting Death, Serious Adverse Events (SAEs) and Adverse Events (AEs) Above 5% Frequency, From Baseline to 4 Weeks

An adverse event is any unwanted event, whether related to study drug or not occuring during the study period. A Serious Adverse Event (SAE) is an event resulting in death, requiring or prolonging hospitalization, a congenital anomaly or other important medical event. AEs and SAEs were recorded at each visit. (NCT01068860)
Timeframe: Baseline, 4 weeks

,,,,,,,,,
Interventionparticipants (Number)
Number of Participants with Serious Adverse EventsNumber of Participants with Non-serious AEs > 5%
Canakinumab 150 mg + Insulin06
Canakinumab 150 mg + Metformin00
Canakinumab 150 mg + Metformin + Sulfonylurea06
Canakinumab 150 mg Canakinumab 150 mg + Met + Sulfonyl + Thia04
Canakinumab 150 mg in Participants With IGT00
Placebo + Insulin03
Placebo + Met + Sulfonyl + Thiaz03
Placebo + Metformin04
Placebo + Metformin + Sulfonylurea03
Placebo in Participants With IGT00

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Pharmacokinetics of Tolbutamide, Staggered Dosing in Period 3, Area Under the Curve (AUC 0-∞)

AUC0-∞ is defined as the area under the concentration time curve from time 0 to infinity. (NCT01185548)
Timeframe: Period 3 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 24, 48, 96, and 264 hours post tolbutamide dose

Interventionnanogram*hour per milliliter (ng*hr/mL) (Geometric Mean)
Tasisulam and Tolbutamide: Period 32700000

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Pharmacokinetics of Tolbutamide, Observed Time at Maximal Concentration (Tmax)

(NCT01185548)
Timeframe: Period 1, 2, and 3 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 4.5, 6, 8, 24, 48, 72, 96, 120, 168, 264, 336 hours post tolbutamide dose

Interventionhours (Median)
Period 1: Tolbutamide2.25
Period 2: Tasisulam and Tolbutamide5.00
Period 3: Tasisulam and Tolbutamide5.02

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Pharmacokinetics of Tolbutamide, Maximum Concentration (Cmax)

(NCT01185548)
Timeframe: Period 1, 2, and 3 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 4.5, 6, 8, 24, 48, 72, 96, 120, 168, 264, 336 hours post tolbutamide dose

Interventionnanogram per milliliter (ng/mL) (Geometric Mean)
Tolbutamide: Period 139600
Tasisulam and Tolbutamide: Period 239800
Tasisulam and Tolbutamide: Period 348000

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Pharmacokinetics of Tolbutamide, Concurrent Dosing, Area Under the Curve (AUC 0-∞)

AUC0-∞ is defined as the area under the concentration time curve from time 0 to infinity. (NCT01185548)
Timeframe: Period 2 Predose; and 0.5, 1, 1.5, 2, 2.5, 3, 4, 4.5, 6, 8, 24, 48, 72, 120, 168, 336 hours post tolbutamide dose

Interventionnanograms*hour per milliliter (ng*hr/mL) (Geometric Mean)
Period 2: Tasisulam and Tolbutamide2670000

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C6hr of Deleobuvir Reduction Metabolite CD 6168

Concentration of an analyte in plasma at 6 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 14)
Group ANA69803360
Group B2250102007460

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Cmax of 1-OH-Midazolam (1-hydroxy-midazolam)

Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 1 (N=16, 19)Day 9 (N=15, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group A5.576.506.465.05
Group B6.686.525.024.67

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Cmax of Deleobuvir (BI 207127)

Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group ANA2700010100
Group B109003140016000

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Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)

Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group ANA127003790
Group B5620202006550

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Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)

Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group ANA596386
Group B2031130806

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Cmax of Deleobuvir Reduction Metabolite CD 6168

Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group ANA85204510
Group B3040124008880

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Cmax of Faldaprevir (BI 201335)

Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionng/mL (Geometric Mean)
Day 9 (N=15,0)Day 17 (N=14,14)Day 66 (N=13,15)
Group A352087804410
Group BNA99506690

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Cmax of Midazolam

Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 1 (N=16, 19)Day 9 (N=15, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group A21.129.931.921.3
Group B23.829.828.823.2

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Number of Participants With Sustained Virological Response (SVR12)

Sustained virologic response (SVR12): Plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level <25 IU/mL(international units per millilitre) undetectable at 12 weeks after the end of treatment. SVR12 was analyzed in a descriptive manner using frequency of participants who achieved SVR12. (NCT01525628)
Timeframe: 12 weeks post treatment

InterventionParticipants (Number)
Group A13
Group B13
Group C11
Group D10
Group E3

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Cmax of Tolbutamide

Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 1 (N=16, 19)Day 9 (N=15, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group A152000146000130000110000
Group B170000158000126000127000

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Cmax of Caffeine

Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.

,
Interventionng/mL (Geometric Mean)
Day 1 (N=16, 19)Day 9 (N=15, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group A5170489048305590
Group B5340722065306450

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Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionng*h/mL (Geometric Mean)
Day 9 (N=15,0)Day 17 (N=14,19)Day 66 (N=13,15)
Group A4560013800056200
Group BNA17300097300

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AUC 0-6hr of Deleobuvir (BI 207127)

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol*h/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group ANA11900036200
Group B4110013500059200

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AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol*h/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group ANA6180015000
Group B243009880027600

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AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol*h/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group ANA29801620
Group B89357003510

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AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol*h/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group ANA4170019300
Group B133006220039100

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AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam)

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.

,
Interventionnmol*h/L (Geometric Mean)
Day 1 (N=16, 19)Day 9 (N=15, 17)Day 17 (N=14, 19)Day 66 (N=13, 13)
Group A23.624.223.518.3
Group B26.028.522.820.8

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AUC 0-infinity of Caffeine

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.

,
Interventionng*h/mL (Geometric Mean)
Day 1 (N=16, 19)Day 9 (N=15, 15)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group A549004210071900120000
Group B77500142000170000159000

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AUC 0-infinity of Midazolam

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.

,
Interventionnmol*h/L (Geometric Mean)
Day 1 (N=16, 19)Day 9 (N=15, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group A79.711712775.5
Group B10713014095.6

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AUC 0-infinity of Tolbutamide

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.

,
Interventionnmol*h/L (Geometric Mean)
Day 1 (N=16, 19)Day 9 (N=13, 17)Day 17 (N=14, 18)Day 66 (N=12, 15)
Group A1940000180000015200001330000
Group B2220000194000014100001390000

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C24hr of Faldaprevir (BI 201335)

Concentration of an analyte in plasma at 24 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionng/mL (Geometric Mean)
Day 9 (N=15,0)Day 17 (N=14,19)Day 66 (N=13,14)
Group A98336701140
Group BNA54102580

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C6hr of Deleobuvir (BI 207127)

Concentration of an analyte in plasma at 6 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 14)
Group ANA179005080
Group B58002080010100

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C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)

Concentration of an analyte in plasma at 6 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 14)
Group ANA112002740
Group B4330175005780

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C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)

Concentration of an analyte in plasma at 6 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 14)
Group ANA508295
Group B159962712

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Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam

Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15). (NCT03291288)
Timeframe: Baseline to 15 days post treatment

Interventionng*hour/mL (Mean)
Part 1: Midazolam Only43.7
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1)31.6
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11)18.5

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Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam Metabolite, 1-Hydroxy Midazolam

Plasma samples for midazolam and 1-hydroxy midazolam were to be collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 (±10 min up to 8 h), 10 (±2), 24 (±2), and 48 (±2) hours on Days 1 to 3 and also when co-administered with pexidartinib on Days 3 to 5 and Days 13 to 15. (NCT03291288)
Timeframe: Baseline to 13 days post treatment

Interventionng*hour/mL (Mean)
Part 1: Midazolam Only200
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1)206
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11)212

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Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Tolbutamide

Plasma samples for tolbutamide were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 h (±10 min up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15). (NCT03291288)
Timeframe: Baseline to 15 days post treatment

Interventionng*hour/mL (Mean)
Part 1: Tolbutamide Only500000
Part 1: Pexidartinib + Tolbutamide (Cycle 1, Day 1)585000
Part 1: Pexidartinib + Tolbutamide (Cycle 1, Day 11)700000

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Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam

Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15). (NCT03291288)
Timeframe: Baseline to 15 days post treatment

Interventionng/mL (Mean)
Part 1: Midazolam Only13.6
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1)12.0
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11)9.7

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Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam Metabolite, 1-Hydroxy Midazolam

Plasma samples for midazolam and 1-hydroxy midazolam were to be collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 (±10 min up to 8 h), 10 (±2), 24 (±2), and 48 (±2) hours on Days 1 to 3 and also when co-administered with pexidartinib on Days 3 to 5 and Days 13 to 15. (NCT03291288)
Timeframe: Baseline to 13 days post treatment

Interventionng/mL (Mean)
Part 1: Midazolam Only49.7
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1)52.1
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11)55.7

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Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Tolbutamide

Plasma samples for tolbutamide were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 h (±10 min up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15). (NCT03291288)
Timeframe: Baseline to 15 days post treatment

Interventionng/mL (Mean)
Part 1: Tolbutamide Only44400
Part 1: Pexidartinib + Tolbutamide (Cycle 1, Day 1)46700
Part 1: Pexidartinib + Tolbutamide (Cycle 1, Day 11)44400

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Pharmacokinetic Analysis: Metabolite to Parent Ratio (MPR) for Midazolam

"Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).~Plasma pharmacokinetic parameters calculated for Midazolam metabolite. 1-hydroxy midazolam and midazolam for the MPR value." (NCT03291288)
Timeframe: Baseline to 13 days post treatment

InterventionRatio (Mean)
Part 1: Midazolam Only587
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1)750
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11)1220

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Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam

Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15). (NCT03291288)
Timeframe: Baseline to 15 days post treatment

Interventionhours (Median)
Part 1: Midazolam Only0.525
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1)0.5
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11)0.5

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Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Tolbutamide

Plasma samples for tolbutamide were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 h (±10 min up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15). (NCT03291288)
Timeframe: Baseline to 15 days post treatment

Interventionhours (Median)
Part 1: Tolbutamide Only2.90
Part 1: Pexidartinib + Tolbutamide (Cycle 1, Day 1)2.94
Part 1: Pexidartinib + Tolbutamide (Cycle 1, Day 11)3.17

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Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam Metabolite, 1-Hydroxy Midazolam

Plasma samples for midazolam and 1-hydroxy midazolam were to be collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 (±10 min up to 8 h), 10 (±2), 24 (±2), and 48 (±2) hours on Days 1 to 3 and also when co-administered with pexidartinib on Days 3 to 5 and Days 13 to 15. (NCT03291288)
Timeframe: Baseline to 13 days post treatment

Interventionhours (Median)
Part 1: Midazolam Only1.0
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1)0.933
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11)0.833

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Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Pexidartinib and ZAAD-1006a Metabolite

Plasma samples for pexidartinib and its metabolite were collected at predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, and 10 (±1) h after the first dose on Day 3, and at steady state when co-administered with midazolam and tolbutamide on Day 13. (NCT03291288)
Timeframe: Baseline to 13 days post treatment

,
Interventionhours (Median)
PexidartinibZAAD-1006a
Part 1: Pexidartinib (Cycle 1, Day 1)2.036.04
Part 1: Pexidartinib (Cycle 1, Day 11)1.932.53

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Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Pexidartinib and ZAAD-1006a Metabolite

Plasma samples for pexidartinib and its metabolite were collected at predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, and 10 (±1) h after the first dose on Day 3, and at steady state when co-administered with midazolam and tolbutamide on Day 13. (NCT03291288)
Timeframe: Baseline to 13 days post treatment

,
Interventionng/mL (Mean)
PexidartinibZAAD-1006a
Part 1: Pexidartinib (Cycle 1, Day 1)31403330
Part 1: Pexidartinib (Cycle 1, Day 11)832013500

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Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Pexidartinib and ZAAD-1006a Metabolite

Plasma samples for pexidartinib and its metabolite were collected at predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, and 10 (±1) h after the first dose on Day 3, and at steady state when co-administered with midazolam and tolbutamide on Day 13. (NCT03291288)
Timeframe: Baseline to 13 days post treatment

,
Interventionng*hour/mL (Mean)
PexidartinibZAAD-1006a
Part 1: Pexidartinib (Cycle 1, Day 1)1440018300
Part 1: Pexidartinib (Cycle 1, Day 11)53200102000

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Overall Summary of Treatment-emergent Adverse Events

Adverse events that emerge during treatment, having been absent pre-treatment, or worsens relative to the pre-treatment state. (NCT03291288)
Timeframe: Baseline to 1 year post treatment

,
InterventionParticipants (Count of Participants)
TEAEsPexidartinib-related TEAEsTreatment-emergent serious adverse events (SAEs)Pexidartinib-related SAEs
Part 1: Drug-drug Interaction Phase241651
Part 2: Pexidartinib Only232051

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Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Tolbutamide Administered With and Without Ritlecitinib

AUCinf was defined as area under the plasma concentration time profile from time 0 extrapolated to infinite time. (NCT05097716)
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, and 36 hours post-dose in Period 1 (Days 1 and 2) and Period 2 (Days 10 and 11)

Interventionng*hr/mL (Geometric Mean)
Period 1: Tolbutamide608600
Period 2: Ritlecitinib + Tolbutamide586500

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Maximum Plasma Concentration (Cmax) of Tolbutamide Administered With and Without Ritlecitinib

Cmax was defined as maximum observed plasma concentration. The determination method of Cmax was observing directly from data. (NCT05097716)
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, and 36 hours post-dose of tolbutamide in Period 1 (Days 1 and 2) and Period 2 (Days 10 and 11)

Interventionng/mL (nanogram/milliliter) (Geometric Mean)
Period 1: Tolbutamide44240
Period 2: Ritlecitinib + Tolbutamide45740

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