Page last updated: 2024-12-10

codeine

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FloraRankFlora DefinitionFamilyFamily Definition
PapavergenusA genus of Eurasian herbaceous plants, the poppies (family PAPAVERACEAE of the dicotyledon class Magnoliopsida), that yield OPIUM from the latex of the unripe seed pods.[MeSH]PapaveraceaeThe poppy plant family of the order Papaverales, subclass Magnoliidae, class Magnoliopsida. These have bisexual, regular, cup-shaped flowers with one superior pistil and many stamens; 2 or 3 conspicuous, separate sepals and a number of separate petals. The fruit is a capsule. Leaves are usually deeply cut or divided into leaflets.[MeSH]
Papaver somniferumspecies[no description available]PapaveraceaeThe poppy plant family of the order Papaverales, subclass Magnoliidae, class Magnoliopsida. These have bisexual, regular, cup-shaped flowers with one superior pistil and many stamens; 2 or 3 conspicuous, separate sepals and a number of separate petals. The fruit is a capsule. Leaves are usually deeply cut or divided into leaflets.[MeSH]

Cross-References

ID SourceID
PubMed CID5284371
CHEMBL ID485
CHEMBL ID369475
CHEBI ID16714
SCHEMBL ID3257
MeSH IDM0004700

Synonyms (113)

Synonym
codeine base
(1s,5r,13r,14s,17r)-10-methoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7,9,11(18),15-tetraen-14-ol
gtpl1673
codicept
coducept
l-codeine
morphine monomethyl ether
(-)-codeine
codein
CHEBI:16714 ,
3-methoxy-17-methyl-7,8-didehydro-4,5alpha-epoxymorphinan-6alpha-ol
o(3)-methylmorphine
morphine 3-methyl ether
(1s,13r,14s,17r)-10-methoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10,15-tetraen-14-ol
methylmorphine
morphine-3-methyl ether
codeina
codeine anhydrous
7,8-didehydro-4,5alpha-epoxy-3-methoxy-17-methylmorphinan-6alpha-ol
(5alpha,6alpha)-17-methyl-3-(methyloxy)-7,8-didehydro-4,5-epoxymorphinan-6-ol
7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol
o3-methylmorphine
morphinan-6-ol, 7,8-didehydro-4,5-epoxy-3-methoxy-17-methyl-, (5alpha,6alpha)- (9ci)
morphinan-6-ol, 7,8-didehydro-4,5-epoxy-3-methoxy-17-methyl-, (5alpha,6alpha)-
morphinan-6alpha-ol, 7,8-didehydro-4,5alpha-epoxy-3-methoxy-17-methyl- (8ci)
hsdb 3043
ccris 7555
morphine-3-methyl ester
morphinan-6-alpha-ol, 7,8-didehydro-4,5-alpha-epoxy-3-methoxy-17-methyl-
n-methylnorcodeine
n-methyl norcodine
norcodine, n-methyl
metilmorfina
7,8-didehydro-4,5-alpha-epoxy-3-methoxy-17-methylmorphinan-6-alpha-ol
norcodeine, n-methyl
3-o-methylmorphine monohydrate
morphinan-6alpha-ol, 7,8-didehydro-4,5alpha-epoxy-3-methoxy-17-methyl-
morphinan-6-ol, 7,8-didehydro-4,5-epoxy-3-methoxy-17-methyl-, (5-alpha,6-alpha)-
einecs 200-969-1
C06174
76-57-3
(5alpha,6alpha)-7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol
codeine ,
codeine polistirex
DB00318
codeinum
n methylmorphine
AC-11114
dea no. 9050
ids-nc-005(sect.-2)
CHEMBL485
codeinum monohydricum
bdbm50105098
CHEMBL369475 ,
10-methoxy-4-methyl-(1s,5r,13r,14s,17r)-12-oxa-4-azapentacyclo[9.6.1.01,13.05,17.07,18]octadeca-7(18),8,10,15-tetraen-14-ol(codeine (h3po4))
10-methoxy-4-methyl-(1s,5r,13r,14s,17r)-12-oxa-4-azapentacyclo[9.6.1.01,13.05,17.07,18]octadeca-7(18),8,10,15-tetraen-14-ol(codeine)
(codeine)
10-methoxy-4-methyl-(13r,14s)-12-oxa-4-azapentacyclo[9.6.1.01,13.05,17.07,18]octadeca-7(18),8,10-trien-14-ol(dihydrocodeine)
10-methoxy-4-methyl-(1s,5r,13r,14s,17r)-12-oxa-4-azapentacyclo[9.6.1.01,13.05,17.07,18]octadeca-7(18),8,10,15-tetraen-14-ol[codeine]
10-methoxy-4-methyl-(1s,5r,13r,14s,17r)-12-oxa-4-azapentacyclo[9.6.1.01,13.05,17.07,18]octadeca-7(18),8,10,15-tetraen-14-ol(codeine phosphate)
10-methoxy-4-methyl-(1s,5r,13r,14s,17r)-12-oxa-4-azapentacyclo[9.6.1.01,13.05,17.07,18]octadeca-7(18),8,10,15-tetraen-14-ol phosphate(codeine)
(codeine)10-methoxy-4-methyl-(1s,5r,13r,14s,17r)-12-oxa-4-azapentacyclo[9.6.1.01,13.05,17.07,18]octadeca-7(18),8,10,15-tetraen-14-ol
bdbm50019351
10-methoxy-4-methyl-(1s,5r,13r,14s,17r)-12-oxa-4-azapentacyclo[9.6.1.01,13.05,17.07,18]octadeca-7(18),8,10,15-tetraen-14-ol
NCGC00248518-01
tox21_200082
cas-76-57-3
dtxsid2020341 ,
NCGC00257636-01
dtxcid40341
AKOS015955539
unii-q830pw7520
codeine [inn:ban]
unii-ux6owy2v7j
ux6owy2v7j ,
codeine polistirex [usan]
tuzistra component of codeine
lean
codeine component of tuzistra
EPITOPE ID:120369
hydrocodone hydrogen tartrate 2.5-hydrate impurity c [ep impurity]
morphine hydrochloride impurity a [ep impurity]
kodelak fito
ethylmorphine hydrochloride impurity c [ep impurity]
codeine [mi]
morphine sulfate impurity a [ep impurity]
dihydrocodeine hydrogen tartrate impurity a [ep impurity]
ss85u8k5zn
codeine [who-dd]
mytussin
codeine [hsdb]
SCHEMBL3257
OROGSEYTTFOCAN-DNJOTXNNSA-N
(1s,5r,13r,14s,17r)-10-methoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10,15-tetraen-14-ol
codeine, european pharmacopoeia (ep) reference standard
codeine 1.0 mg/ml in methanol
codeine anhydrate
codeine 0.1 mg/ml in methanol
Q174723
(4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinolin-7-ol
codeine (crm)
(1s,5r,13r,14s,17r)-10-methoxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0?,??.0?,??.0?,??]octadeca-7,9,11(18),15-tetraen-14-ol
(1s,13r,14s,17r)-10-methoxy-4-methyl-12-oxa-4-azapentacyclo(9.6.1.0(1,13).0(5,17).0(7,18))octadeca-7(18),8,10,15-tetraen-14-ol
n-methyl-nordoceine
dihydrocodeine hydrogen tartrate impurity a (ep impurity)
7,8-didehydro-4,5-epoxy-3-methoxy-17-methyl-(5 alpha, 6 alpha)-morphinan 6-ol
hydrocodone hydrogen tartrate 2.5-hydrate impurity c (ep impurity)
codeine monohydrate (ep monograph)
morphinan-6-ol, 7,8-didehydro-4,5-epoxy-3-methoxy-17-methyl-(5 alpha, 6
codeine (usp monograph)
codeine (mart.)
norcodeine, n-methyl-
831 - opiates in poppy seeds

Research Excerpts

Overview

Codeine is a first-line treatment for pain and needs to be metabolized into morphine by cytochrome 2D6 to exert its analgesic effect. Codeine dependence is a significant public health problem, motivating the recent rescheduling of codeine in Australia (1 February 2018) Codeine is an unpredictable analgesic because of its variable pharmacokinetic, pharmacodynamic, and pharmacogenetic properties.

ExcerptReferenceRelevance
"Codeine N-oxide 2 is an active metabolite of codeine obtained by oxidation and observed as a degradant in codeine drug products such as syrups. "( Complete
Boccadifuoco, G; Boiteau, JG; Dufaÿ, S; Mouis, G; Reverse, K; Surget, E, 2022
)
2.16
"Codeine is an effective and generally well-tolerated antitussive for chronic cough. "( Effectiveness and Safety of Codeine and Levodropropizine in Patients With Chronic Cough.
Kang, SY; Lee, BJ; Lee, SM; Lee, SP, 2022
)
2.46
"Codeine dependence is a significant public health problem, motivating the recent rescheduling of codeine in Australia (1 February 2018). "( Identifying and treating codeine dependence: a systematic review.
Johnson, JL; MacDonald, T; Nielsen, S, 2018
)
2.23
"Codeine is a first-line treatment for pain and needs to be metabolized into morphine by cytochrome 2D6 to exert its analgesic effect."( Interaction between CYP2D6 inhibitor antidepressants and codeine: is this relevant?
Bulteau, S; Caillet, P; Cazet, L; Chaslerie, A; Evin, A; Jolliet, P; Kuhn, E; Pivette, J; Spiers, A; Victorri-Vigneau, C, 2018
)
1.45
"Codeine is an analgesic drug acting on μ-opioid receptors predominantly via its metabolite morphine formed almost exclusively by CYP2D6. "( The impact of CYP2D6 polymorphisms on the pharmacokinetics of codeine and its metabolites in Mongolian Chinese subjects.
Guo, T; Lv, J; Wu, X; Yuan, L; Zuo, J, 2014
)
2.09
"Codeine is an unpredictable analgesic because of its variable pharmacokinetic, pharmacodynamic, and pharmacogenetic properties. "( A single institution's effort to translate codeine knowledge into specific clinical practice.
Berde, C; Jerome, J; McHale, J; Sethna, N; Solodiuk, JC, 2014
)
2.11
"Codeine is a mild opioid widely used as an analgesic in various age groups, including various pediatric settings. "( Doing without codeine: why and what are the alternatives?
Barbi, E; Benini, F, 2014
)
2.21
"Codeine is a widely used opioid, which is metabolized to morphine to elicit analgesia."( Codeine-induced hyperalgesia and allodynia: investigating the role of glial activation.
Bobrovskaya, L; Hutchinson, MR; Johnson, JL; Johnson, K; Johnson, ME; Rolan, PE; Tuke, J; Williams, DB, 2014
)
2.57
"Codeine is an opioid, which elicits its analgesic effects via metabolism to morphine and codeine-6-glucuronide."( A Compartmental Analysis for Morphine and Its Metabolites in Young Children After a Single Oral Dose.
Aleksa, K; Carleton, BC; Castañeda-Hernandez, G; Cooke, E; Dawes, J; Gonzalez-Ramirez, R; Jacobo-Cabral, CO; Jimenez-Mendez, R; Koren, G; Montgomery, CJ; Rieder, MJ; Velez de Mendizabal, N, 2015
)
1.14
"Codeine is a widely used analgesic, that is available for sale in pharmacies over the counter (OTC) in a number of countries including the UK, South Africa, Ireland, France and Australia. "( Over-the-Counter Codeine-from Therapeutic Use to Dependence, and the Grey Areas in Between.
Nielsen, S; Van Hout, MC, 2017
)
2.24
"Codeine is a drug that until recently was widely used in children. "( Codeine in paediatrics: pharmacology, prescribing and controversies.
Andrzejowski, P; Carroll, W, 2016
)
3.32
"Codeine is a widely used opioid analgesic but studies on its misuse in chronic noncancer pain (CNCP) are still lacking. "( Codeine Shopping Behavior in a Retrospective Cohort of Chronic Noncancer Pain Patients: Incidence and Risk Factors.
Authier, N; Chenaf, C; Delage, N; Delorme, J; Eschalier, A; Kabore, JL; Mulliez, A; Pereira, B; Roche, L, 2016
)
3.32
"Codeine is a prodrug with little inherent pharmacologic activity and must be metabolized in the liver into morphine, which is responsible for codeine's analgesic effects."( Codeine: Time to Say "No".
Coté, CJ; Green, TP; Tobias, JD, 2016
)
2.6
"Codeine is a common drug widely used in some countries as a pain reliever. "( Inhibitory Effect of Codeine on Sucrase Activity
AavaniSucrase,, T; Minai-Tehrani, D; Minoui, S; Sepehre, M; Sharifkhodaei, Z, 2009
)
2.11
"Codeine is an opioid metabolised to active analgesic compounds, including morphine. "( Single dose oral codeine, as a single agent, for acute postoperative pain in adults.
Derry, S; McQuay, HJ; Moore, RA, 2010
)
2.14
"Codeine is an important opioid anti-tussive agent whose short half-life (2.9 ± 0.7 h) requires that it be administered at 4-h intervals when formulated as a simple aqueous solution. "( Pharmacokinetics of a novel liquid controlled release codeine formulation.
Beubler, E; Dittrich, P; Haltmeyer, K; Roblegg, E; Zimmer, A, 2011
)
2.06
"Codeine is an old and commonly used analgesic agent for mild to moderate pain. "( Is there a role for therapeutic drug monitoring with codeine?
Kelly, LE; Madadi, P, 2012
)
2.07
"Codeine is a potent μ-opioid receptor agonist."( Naloxone blocks suppression of cough by codeine in anesthetized rabbits.
Poliacek, I; Simera, M; Veternik, M, 2013
)
1.38
"Codeine is a lawfully permitted ingredient of over-the-counter cold and cough medicines readily available to the public in Taiwan. "( The effect of codeine in anti-cough syrup on morphine screen.
Hsu, CL; Hung, DZ; Yang, DY, 2002
)
2.12
"Codeine is an opioid analgesic. "( Codeine phosphate-induced hypersensitivity syndrome.
Enomoto, M; Kamo, R; Ochi, M; Taguchi, S; Teramae, K; Yamane, T, 2004
)
3.21
"Codeine is an opiate with uncertain and unpredictable effects. "( [Problem forte--is paracetamol-codeine combination rational?].
Helland, A; Slørdal, L; Spigset, O, 2004
)
2.05
"Codeine is a frequently used opioid analgesic, especially when pain control with acetaminophen or nonsteroidal antiinflammatory drugs fails. "( Probable codeine phosphate-induced seizures.
Kao, SM; Kuo, SC; Lin, YC; Yang, YH, 2004
)
2.18
"Codeine is an analgesic with uses similar to morphines, but it is of much less effect, i.e., it had a mild sedative effect; codeine is usually used as the phosphate form (Cod.P) and is often administrated by mouth with aspirin of paracetamol. "( The use of IR, magnetism, reflectance, and mass spectra together with thermal analyses in structure investigation of codeine phosphate complexes of d-block elements.
Abdullah, SM; El-shahat, MF; Zayed, MA, 2005
)
1.98
"Codeine is an analgesic with uses similar to morphine, but it has a mild sedative effect. "( Structure investigation of codeine drug using mass spectrometry, thermal analyses and semi-emperical molecular orbital (MO) calculations.
Fahmey, MA; Hawash, MF; Zayed, MA, 2006
)
2.07
"Codeine is a much weaker agonist at mu opioid receptors than morphine."( Response to hydrocodone, codeine and oxycodone in a CYP2D6 poor metabolizer.
de Leon, J; Murray-Carmichael, E; Susce, MT, 2006
)
1.36
"Codeine is an analgesic drug acting on mu-opiate receptors predominantly via its metabolite morphine, which is formed almost exclusively by the genetically polymorphic enzyme cytochrome P450 2D6 (CYP2D6). "( Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 duplication.
Brockmöller, J; Keulen, JT; Kirchheiner, J; Lötsch, J; Roots, I; Schmidt, H; Tzvetkov, M, 2007
)
2.11
"Codeine is a relatively high-extraction drug that is primarily eliminated by metabolism in the liver."( Codeine disposition in sickle cell patients compared with healthy volunteers.
Ayass, M; Derendorf, H; Gross, S; Kedar, A; Mehta, P; Mohammed, SS, 1993
)
2.45
"Codeine is an analgesic commonly used to relieve pain in the early post partum. "( Codeine and the breastfed neonate.
Alger, LS; Brill-Miller, JL; Brown, S; Meny, RG; Naumburg, EG, 1993
)
3.17
"Codeine is an old drug that is still widely used to treat mild and moderate pain. "( The pharmacogenetics of codeine hypoalgesia.
Brøsen, K; Sindrup, SH, 1995
)
2.04
"Codeine is a substrate of CYP2D6, a genetically polymorphic P450 enzyme, and is metabolized to the more potent drug morphine."( Cytochrome P450 2D6 and treatment of codeine dependence.
Otton, SV; Romach, MK; Sellers, EM; Somer, G; Tyndale, RF, 2000
)
1.3
"Codeine is a popular opioid prodrug dependent on the activity of the specific cytochrome P450 enzyme 2D6 (CYP2D6). "( Variable cytochrome P450 2D6 expression and metabolism of codeine and other opioid prodrugs: implications for the Australian anaesthetist.
Owen, H; Wilcox, RA, 2000
)
1.99

Effects

Codeine has a spasmodic effect on sphincter of Oddi and is suspected to cause acute pancreatitis. Codeine has an identified abuse liability, given its effect and development of tolerance within a short timeframe on regular or excessive use.

Codeine treatment has been shown to be associated with glucolipid deregulation. Codeine has an advantage as an antitussive because of its multifaceted effect as an analgesic and sedative along with cough suppression.

ExcerptReferenceRelevance
"Codeine has a spasmodic effect on sphincter of Oddi and is suspected to cause acute pancreatitis in patients with a history of cholecystectomy."( Increased Risk of Acute Pancreatitis with Codeine Use in Patients with a History of Cholecystectomy.
Brumback, BA; Hartzema, A; Johnson, GD; Kim, J; Tabner, AJ, 2020
)
2.27
"Codeine has an identified abuse liability, given its effect and development of tolerance within a short timeframe on regular or excessive use."( Misuse of non-prescription codeine containing products: Recommendations for detection and reduction of risk in community pharmacies.
Norman, I; Van Hout, MC, 2016
)
1.45
"Codeine has an advantage as an antitussive because of its multifaceted effect as an analgesic and sedative along with cough suppression."( Codeine: A Relook at the Old Antitussive.
Nadkar, MY; Vora, A, 2015
)
2.58
"Codeine has a weaker pharmacological effects and our results suggest that codeine maintenance treatment deserves more attention and controlled trials to assess the benefits compared with methadone (or other opioids)."( Maintenance treatment of opiate addicts in Germany with medications containing codeine--results of a follow-up study.
Degkwitz, P; Haasen, C; Krausz, M; Raschke, P; Verthein, U, 1998
)
1.25
"Codeine has been partly replaced by tramadol."( Opioid Analgesic Prescription in French Children: A National Population-Based Study.
Authier, N; Chenaf, C; Choufi, S; Delorme, J; Merlin, E; Mounier, S; Rochette, E, 2021
)
1.34
"Codeine has a spasmodic effect on sphincter of Oddi and is suspected to cause acute pancreatitis in patients with a history of cholecystectomy."( Increased Risk of Acute Pancreatitis with Codeine Use in Patients with a History of Cholecystectomy.
Brumback, BA; Hartzema, A; Johnson, GD; Kim, J; Tabner, AJ, 2020
)
2.27
"Codeine treatment has been shown to be associated with glucolipid deregulation, though data reporting this are inconsistent and the mechanisms are not well understood. "( Codeine exerts cardiorenal injury via upregulation of adenine deaminase/xanthine oxidase and caspase 3 signaling.
Ajayi, AF; Ajayi, LO; Akhigbe, RE, 2021
)
3.51
"Codeine misuse has emerged as a concerning public health issue due to its associated adverse effects such as headache, nausea, vomiting, and hemorrhage."( A Review of Analytical Methods for Codeine Determination.
Carrão, DB; Fauziati, R; Gandhi, FA; Majid, MA; Noviana, E; Pratiwi, R; Saputri, FA, 2021
)
1.62
"Codeine elixir has long been used for pain relief, but has recently been banned by the Food and Drug Administration due to a recently recognized risk of death."( Acupuncture instead of codeine for tonsillectomy pain in children.
Ochi, JW, 2013
)
1.42
"Codeine has an identified abuse liability, given its effect and development of tolerance within a short timeframe on regular or excessive use."( Misuse of non-prescription codeine containing products: Recommendations for detection and reduction of risk in community pharmacies.
Norman, I; Van Hout, MC, 2016
)
1.45
"Codeine has an advantage as an antitussive because of its multifaceted effect as an analgesic and sedative along with cough suppression."( Codeine: A Relook at the Old Antitussive.
Nadkar, MY; Vora, A, 2015
)
2.58
"Codeine has been prescribed to pediatric patients for many decades as both an analgesic and an antitussive agent. "( Codeine: Time to Say "No".
Coté, CJ; Green, TP; Tobias, JD, 2016
)
3.32
"Codeine has been used medicinally since the 1800s as an analgesic and antitussive agent. "( Pharmacogenetic insights into codeine analgesia: implications to pediatric codeine use.
Koren, G; Madadi, P, 2008
)
2.08
"Codeine has opioid-related adverse effects and may not be safe during breastfeeding in the postpartum period for all neonates."( Codeine-acetaminophen versus nonsteroidal anti-inflammatory drugs in the treatment of post-abdominal surgery pain: a systematic review of randomized trials.
Koren, G; Landsmeer, ML; Nauta, M, 2009
)
2.52
"Codeine has become a controversial choice for analgesia in children compared with other commonly available drugs."( Analgesic prescribing practices can be improved by low-cost point-of-care decision support.
Auerbach, AD; Maselli, JH; Rosenbluth, G; Wilson, SD, 2011
)
1.81
"Codeine has little therapeutic effect in patients who are CYP2D6 poor metabolizers, whereas the risk of morphine toxicity is higher in ultrarapid metabolizers."( Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype.
Callaghan, JT; Crews, KR; Dunnenberger, HM; Gaedigk, A; Kharasch, ED; Klein, TE; Shen, DD; Skaar, TC, 2012
)
1.33
"Codeine and morphine have been detected in mammalian brain by radioimmunoassay (RIA), and in brain and other tissues by gas-chromatography/mass-spectrometry (GCMS) in different laboratories. "( Endogenous codeine and morphine are stored in specific brain neurons.
Alessandrini, C; Bianchi, E; Guarna, M; Tagliamonte, A, 1993
)
2.12
"Codeine has a weaker pharmacological effects and our results suggest that codeine maintenance treatment deserves more attention and controlled trials to assess the benefits compared with methadone (or other opioids)."( Maintenance treatment of opiate addicts in Germany with medications containing codeine--results of a follow-up study.
Degkwitz, P; Haasen, C; Krausz, M; Raschke, P; Verthein, U, 1998
)
1.25

Actions

Codeine use was lower in children whose ethnicity was not white and those uninsured. Codeine 60 mg may produce a small increase in the analgesic effect of aspirin 650 mg.

ExcerptReferenceRelevance
"Codeine use was lower in children whose ethnicity was not white and those uninsured (OR, 0.47 [0.34-0.63])."( Codeine use among children in the United States: a nationally representative study from 1996 to 2013.
Groenewald, CB; Livingstone, MJ; Palermo, TM; Rabbitts, JA, 2017
)
2.62
"Codeine 60 mg may produce a small increase in the analgesic effect of aspirin 650 mg. "( Do codeine and caffeine enhance the analgesic effect of aspirin?--A systematic overview.
Po, AL; Zhang, WY, 1997
)
2.36

Treatment

Codeine treatment has been shown to be associated with glucolipid deregulation. Data reporting this are inconsistent and the mechanisms are not well understood. Codeine treatment led to reduced absolute and relative cardiac and renal mass independent of body weight change.

ExcerptReferenceRelevance
"The codeine-treated groups received either 4mg/kg b.w of codeine or 10mg/kg b.w of codeine p.o."( Testicular toxicity following chronic codeine administration is via oxidative DNA damage and up-regulation of NO/TNF-α and caspase 3 activities.
Ajayi, A; Akhigbe, R, 2020
)
1.31
"Codeine treatment has been shown to be associated with glucolipid deregulation, though data reporting this are inconsistent and the mechanisms are not well understood. "( Codeine exerts cardiorenal injury via upregulation of adenine deaminase/xanthine oxidase and caspase 3 signaling.
Ajayi, AF; Ajayi, LO; Akhigbe, RE, 2021
)
3.51
"Codeine treatment led to reduced absolute and relative cardiac and renal mass independent of body weight change, increased blood glucose, total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL-C), as well as increased atherogenic indices and triglyceride-glucose index (TyG). "( Codeine exerts cardiorenal injury via upregulation of adenine deaminase/xanthine oxidase and caspase 3 signaling.
Ajayi, AF; Ajayi, LO; Akhigbe, RE, 2021
)
3.51
"The codeine-treated animals had significantly lower levels of serum proteins, increased activities of hepatic enzyme biomarkers and caspase 3, raised hepatic concentrations of free radicals and TNF-α, as well as increased hepatic DNA fragmentation."( Codeine-induced hepatic injury is via oxido-inflammatory damage and caspase-3-mediated apoptosis.
Adelakun, AA; Ajayi, AF; Ajayi, LO; Akhigbe, RE; Olorunnisola, OS, 2020
)
2.48
"CR codeine treatment was rated as moderately or highly acceptable by 82% of patients compared with 50% for acetaminophen plus codeine (P=0.001)."( Evaluation of dosing guidelines for use of controlled-release codeine in chronic noncancer pain.
Arkinstall, W; Clark, AJ; Darke, A; Eisenhoffer, J; Harsanyi, Z; Hays, H; Moulin, D; Quigley, P; Russell, A; Watson, CP, 2003
)
1.07
"Codeine treatment had a significant effect on time spent coughing compared with baseline (P = .02) but not compared with placebo (P = .52)."( Effect of codeine on objective measurement of cough in chronic obstructive pulmonary disease.
Earis, J; Owen, E; Smith, J; Woodcock, A, 2006
)
1.46
"CR codeine treatment resulted in significantly lower overall VAS pain intensity scores (35 +/- 18 vs."( Efficacy of controlled-release codeine in chronic non-malignant pain: a randomized, placebo-controlled clinical trial.
Arkinstall, W; Babul, N; Darke, AC; Goughnour, B; Harsanyi, Z; Sandler, A, 1995
)
1.09
"CR codeine treatment resulted in significantly lower overall VAS pain intensity scores (22 +/- 18 mm versus 36 +/- 20 mm, P = 0.0001), categorical pain intensity scores (1.2 +/- 0.8 versus 1.8 +/- 0.8, P = 0.0001), and pain scores when assessed by day of treatment and by time of day."( Randomized evaluation of controlled-release codeine and placebo in chronic cancer pain.
Arkinstall, WW; Babul, N; Darke, AC; Dhaliwal, HS; Harsanyi, Z; Sloan, P; Thirlwell, MP, 1995
)
1.07

Toxicity

Codeine phosphate is an unpredictable pro-drug that does not equate to a safe and effective method of providing analgesia post-craniotomy. Individual responses and adverse events should be carefully monitored when codeine is used to treat chronic cough.

ExcerptReferenceRelevance
" There was statistical evidence for greater adverse effects of aspirin/codeine on mood and mental alertness in comparison to ibuprofen/codeine and placebo."( Multiple-dose safety study of ibuprofen/codeine and aspirin/codeine combinations.
Friedman, H; Oster, H; Royer, G; Seckman, C; Stubbs, C, 1990
)
0.78
" A single, mild side effect was associated with as much additional pain relief as multiple, severe side effects."( Association of pain relief with drug side effects in postherpetic neuralgia: a single-dose study of clonidine, codeine, ibuprofen, and placebo.
Culnane, M; Dubner, R; Gracely, RH; Max, MB; Schafer, SC, 1988
)
0.49
" Furthermore, the effects on psychomotor function, self-rated subjective feelings, and side effect profile were studied."( Effects of graded oral doses of a new 5-hydroxytryptamine/noradrenaline uptake inhibitor (Ro 15-8081) in comparison with 60 mg codeine and placebo on experimentally induced pain and side effect profile in healthy men.
Abatzi, TA; Gaupmann, G; Mittelbach, G; Schneider, S; Stacher, G; Stacher-Janotta, G; Steinringer, H, 1987
)
0.48
" The predominant adverse experiences associated with ciramadol were nausea and drowsiness, which were apparently not dose related."( Comparison of the analgesic efficacy and safety oral ciramadol, codeine, and placebo in patients with chronic cancer pain.
McAdams, J; Stambaugh, JE, 1987
)
0.51
"The ability of sulfhydryl compounds to provide protection against the acute toxicity of codeinone, a toxic metabolite of codeine, was investigated in mice."( Effects of glutathione and phenobarbital on the toxicity of codeinone.
Inoue, K; Nagamatsu, K; Terao, T; Toki, S, 1986
)
0.48
" The results showed that the combination was no more toxic than paracetamol alone and, on the basis of the LD50:ED50 ratio, was less toxic by the oral than by the rectal route."( Acute toxicity and analgesic action of a combination of buclizine, codeine and paracetamol ('Migraleve') in tablet and suppository form in rats.
Behrendt, WA; Cserepes, J, 1985
)
0.51
"Approximately equianalgesic oral doses of codeine, an oxycodone compound resembling Percodan, and pentazocine were compared for adverse effects in a double-blind, randomized study of four doses of each drug given over two days to 247 postsurgical patients with pain."( Adverse effects of commonly ordered oral narcotics.
Hopper, M; Kantor, TG; Laska, E, 1981
)
0.53
" Adverse events were observed in two patients on moguisteine, three on codeine 15 mg, and five on codeine 30 mg."( The efficacy and safety of moguisteine in comparison with codeine phosphate in patients with chronic cough.
Barnabè, R; Berni, F; Clini, V; Pirrelli, M; Pisani Ceretti, A; Robuschi, M; Rossi, M; Sestini, P; Tana, F; Vaghi, A, 1995
)
0.77
"The sum pain intensity difference (efficacy analysis) and the proportion of patients reporting a side effect (safety analysis)."( Analgesic efficacy and safety of paracetamol-codeine combinations versus paracetamol alone: a systematic review.
de Craen, AJ; Di Giulio, G; Kessels, AG; Kleijnen, J; Lampe-Schoenmaeckers, JE, 1996
)
0.55
" In the multidose studies the proportion of patients reporting a side effect was significantly higher with paracetamol-codeine combinations."( Analgesic efficacy and safety of paracetamol-codeine combinations versus paracetamol alone: a systematic review.
de Craen, AJ; Di Giulio, G; Kessels, AG; Kleijnen, J; Lampe-Schoenmaeckers, JE, 1996
)
0.76
" Adverse effects were rated by a structured interview."( Codeine and morphine in extensive and poor metabolizers of sparteine: pharmacokinetics, analgesic effect and side effects.
Arendt-Nielsen, L; Brøsen, K; Elbaek, K; Gram, LF; Poulsen, L; Sindrup, SH, 1996
)
1.74
" In PMs, adverse effects were significantly more pronounced on morphine than on codeine and only showed a slight difference between codeine and placebo."( Codeine and morphine in extensive and poor metabolizers of sparteine: pharmacokinetics, analgesic effect and side effects.
Arendt-Nielsen, L; Brøsen, K; Elbaek, K; Gram, LF; Poulsen, L; Sindrup, SH, 1996
)
1.96
"This study confirms that codeine O-demethylation depends on CYP2D6; it shows that the 6-glucuronidation of morphine is independent of CYP2D6; it supports the theory that the analgesic effect of codeine depends on its O-demethylation; and it indicates that this is probably also the case for the adverse effects."( Codeine and morphine in extensive and poor metabolizers of sparteine: pharmacokinetics, analgesic effect and side effects.
Arendt-Nielsen, L; Brøsen, K; Elbaek, K; Gram, LF; Poulsen, L; Sindrup, SH, 1996
)
2.04
" Tolerability was evaluated by laboratory results, vital signs and any adverse event occurring during the clinical trial, including presence or absence of somnolence."( Efficacy and safety of levodropropizine and dihydrocodeine on nonproductive cough in primary and metastatic lung cancer.
Barni, S; Daffonchio, L; Luporini, G; Marchi, E, 1998
)
0.55
"Rapid opiate detoxification under general anaesthesia is a safe and efficient method to suppress withdrawal symptoms."( Safety, efficacy, and long-term results of a modified version of rapid opiate detoxification under general anaesthesia: a prospective study in methadone, heroin, codeine and morphine addicts.
Hensel, M; Kox, WJ, 2000
)
0.5
" --It is argued, in this paper, that codeine phosphate is an unpredictable pro-drug that does not equate to a safe and effective method of providing analgesia post-craniotomy."( A review of the efficacy and safety of opioid analgesics post-craniotomy.
Roberts, G,
)
0.4
" Each side effect was recoded into a dichotomous response (i."( Time-contingent dosing of an opioid analgesic after tonsillectomy does not increase moderate-to-severe side effects in children.
Holdridge-Zeuner, D; Lanier, B; Miaskowski, C; Paul, SM; Savedra, MC; Sutters, KA; Waite, S, 2005
)
0.33
"Regardless of the clinical scenario in which they are administered, opioids can have adverse effects in infants and children."( Adverse effects following the inadvertent administration of opioids to infants and children.
Meyer, D; Tobias, JD,
)
0.13
"With the objective of comparing incidence of adverse events of the opioids codeine, hydrocodone, and tramadol in the relief of cancer pain, we conducted a randomized controlled trial in which patients with cancer were randomly assigned according to a computer-generated schedule to receive one of the three opioids."( Incidence of weak opioids adverse events in the management of cancer pain: a double-blind comparative trial.
Bravo, LE; Castillo, JM; Castillo, MP; Castro, F; Daza, P; Montoya, O; Restrepo, JM; Rodriguez, MF; Rodriguez, RF, 2007
)
0.57
" In this situation, newborns might be exposed to toxic levels of morphine when breastfeeding."( Safety of codeine during breastfeeding: fatal morphine poisoning in the breastfed neonate of a mother prescribed codeine.
Aleksa, K; Cairns, J; Chitayat, D; Gaedigk, A; Karaskov, T; Koren, G; Leeder, JS; Madadi, P; Teitelbaum, R, 2007
)
0.74
" Patients were assessed for pain control and adverse events."( Morphine infusions after pediatric cranial surgery: a retrospective analysis of safety and efficacy.
Bowen-Roberts, T; Hammond, AM; Kent, SK; Ou, CH; Steinbok, P; Warren, DT, 2008
)
0.35
"These findings suggest that CMI is as safe a treatment option as acetaminophen and codeine."( Morphine infusions after pediatric cranial surgery: a retrospective analysis of safety and efficacy.
Bowen-Roberts, T; Hammond, AM; Kent, SK; Ou, CH; Steinbok, P; Warren, DT, 2008
)
0.57
"Two goals when counseling breastfeeding mothers taking medication are protecting the infant from adverse events and permitting necessary maternal therapy."( Safety issues of maternal drug therapy during breastfeeding.
Berlin, CM; Paul, IM; Vesell, ES, 2009
)
0.35
"To provide family physicians with a practical clinical summary of the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain, developed by the National Opioid Use Guideline Group."( Canadian guideline for safe and effective use of opioids for chronic noncancer pain: clinical summary for family physicians. Part 1: general population.
Kahan, M; Mailis-Gagnon, A; Srivastava, A; Wilson, L, 2011
)
0.37
" Regarding safety, there were no statistically significant differences between treatment groups in the incidence of adverse events in the dental pain and tension-type headache studies."( Assessment of the efficacy and safety profiles of aspirin and acetaminophen with codeine: results from 2 randomized, controlled trials in individuals with tension-type headache and postoperative dental pain.
Fisher, M; Gatoulis, SC; Voelker, M, 2012
)
0.61
" This study aimed to determine if codeine could be recommended as a safe treatment option for NSAID-hypersensitive patients without the need for oral drug provocation testing."( The safety of codeine in patients with non-steroidal anti-inflammatory drug hypersensitivity: a preliminary study.
Celebioglu, E; Kalyoncu, AF; Karakaya, G,
)
0.77
" I also describe the potential safety signals identified by FDA using its Adverse Event Reporting System, and their importance in ensuring the safe use of drugs in the post-marketing phase."( [Topics from "Overseas Drug Safety Information" in the past five years].
Amanuma, K, 2013
)
0.39
" Taking into account the high consumption of codeine, only few fatal adverse events have been published."( Codeine Ultra-rapid Metabolizers: Age Appears to be a Key Factor in Adverse Effects of Codeine.
Fuchs, W; Heintze, K, 2015
)
2.12
" These effects are thought to result from the toxic components produced as byproducts during the homemade drug synthesis."( The harmful chemistry behind krokodil (desomorphine) synthesis and mechanisms of toxicity.
Afonso, CM; Alves, EA; Carvalho, F; Dinis-Oliveira, RJ; Grund, JP; Netto, AD, 2015
)
0.42
" As the drug is commonly available appropriate titration and dosing and knowledge of its metabolism and possible adverse effects are important for safe prescription of DHC."( Dihydrocodeine: safety concerns.
Leppert, W; Woroń, J, 2016
)
0.89
" Our efforts represent an evidence-based, innovative medication safety strategy to prevent adverse drug events, which is a model for the use of pharmacogenetics to optimize drug therapy in specialized pediatric populations."( Pharmacogenetics for Safe Codeine Use in Sickle Cell Disease.
Baker, DK; Barker, PJ; Broeckel, U; Crews, KR; Estepp, JH; Gammal, RS; Haidar, CE; Hankins, J; Hoffman, JM; Pei, D; Relling, MV; Wang, W; Weiss, MJ, 2016
)
0.73
"Safety concerns regarding potential life-threatening adverse events associated with codeine have resulted in policy decisions to restrict its use in pediatrics."( Impact of Safety-Related Regulations on Codeine Use in Children: A Quasi-Experimental Study Using Taiwan's National Health Insurance Research Database.
Chao, PH; Chen, WW; Hsiao, FY; Huang, WI; Ke, WM; Lin, CW; Wang, CH, 2017
)
0.95
" Future research is warranted to explore whether there was a simultaneous decrease in the incidence rates of codeine-related adverse events following the safety-related regulations."( Impact of Safety-Related Regulations on Codeine Use in Children: A Quasi-Experimental Study Using Taiwan's National Health Insurance Research Database.
Chao, PH; Chen, WW; Hsiao, FY; Huang, WI; Ke, WM; Lin, CW; Wang, CH, 2017
)
0.94
"Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine."( A cost-effectiveness analysis of maternal CYP2D6 genetic testing to guide treatment for postpartum pain and avert infant adverse events.
Berger, H; Ito, S; Koren, G; Lato, DF; Moretti, ME; Ungar, WJ, 2018
)
0.69
"Dihydrocodeine and tramadol are particularly toxic in overdose and codeine is also relatively toxic."( Relative toxicity of analgesics commonly used for intentional self-poisoning: A study of case fatality based on fatal and non-fatal overdoses.
Bankhead, C; Casey, D; Clements, C; Ferrey, A; Fuller, A; Geulayov, G; Gunnell, D; Hawton, K; Kapur, N; Ness, J; Wells, C, 2019
)
0.97
"Xenobiotics biotransformation in humans is a process of the chemical modifications, which may lead to the formation of toxic metabolites."( Metatox - Web application for generation of metabolic pathways and toxicity estimation.
Bezhentsev, V; Dmitriev, A; Filimonov, D; Lagunin, A; Poroikov, V; Rudik, A, 2019
)
0.51
" The incidence of adverse events (AEs) was significantly higher in the AC group compared to NS and PBO."( Efficacy and safety of naproxen sodium 440 mg versus acetaminophen 600 mg/codeine phosphate 60 mg in the treatment of postoperative dental pain.
Cattry, E; Paredes-Diaz, A; Troullos, E, 2020
)
0.79
"6 mg/kg has been shown to generate morphine and M6G concentrations comparable to that observed following administration of clinically effective doses of morphine, without the concomitant adverse effects observed with morphine administration."( Pharmacokinetics, adverse effects and effects on thermal nociception following administration of three doses of codeine to horses.
Gretler, SR; Kass, PH; Knych, HK; McKemie, DS; Stucker, K, 2022
)
0.93
"The current study describes the metabolic profile and pharmacokinetics of codeine in horses and provides information that can be utilized in the design of future studies to understand the anti-nociceptive and analgesic effects of opioids in this species with the goal of promoting judicious and safe use of this important class of drugs."( Pharmacokinetics, adverse effects and effects on thermal nociception following administration of three doses of codeine to horses.
Gretler, SR; Kass, PH; Knych, HK; McKemie, DS; Stucker, K, 2022
)
1.16
" Individual responses and adverse events should be carefully monitored when codeine is used to treat chronic cough."( Effectiveness and Safety of Codeine and Levodropropizine in Patients With Chronic Cough.
Kang, SY; Lee, BJ; Lee, SM; Lee, SP, 2022
)
1.24

Pharmacokinetics

The method was successfully applied to a pharmacokinetic study of codeine in healthy Mongolian Chinese volunteers after a 30 mg oral dose. The mean area under the curve (AUC), half-life and total plasma clearance ofcodeine were 1020 +/- 340 nmol l-1 h, 2. No significant differences were observed in the pharmacokinetics parameters ofCodeine in the three genotype groups.

ExcerptReferenceRelevance
" Mean values of Cmax (445 nmol l-1) and AUC (1660 nmol l-1 h) of codeine in the Chinese were significantly higher than those in the Caucasians (292 nmol l-1 and 1010 nmol l-1 h)."( A comparison of the pharmacokinetics of codeine and its metabolites in healthy Chinese and Caucasian extensive hydroxylators of debrisoquine.
Säwe, J; Sjöqvist, F; Svensson, JO; Yue, QY, 1991
)
0.79
" Codeine exhibits characteristics consistent with a two-compartment pharmacokinetic model."( A dose-ranging study of the pharmacokinetics of codeine phosphate following intravenous administration to rats.
Mason, WD; Shah, J, 1991
)
1.45
"8 ml per min) was significantly lower than that in the young (137 ml per min), and there was a significant correlation between the half-life at single dosing and the blood urea concentration."( The effect of ageing on the pharmacokinetics of dihydrocodeine.
Castleden, CM; Davies, KN; Jagger, C; McBurney, A, 1989
)
0.52
"2 h) and eliminated slowly with a mean half-life of 50."( Pharmacokinetics of pholcodine in healthy volunteers: single and chronic dosing studies.
Bochner, F; Chen, ZR; Somogyi, A, 1988
)
0.27
" Codeine elimination half-life and mean residence time were increased significantly in the hemodialysis group (18."( Pharmacokinetics and pharmacodynamics of codeine in end-stage renal disease.
Abraham, PA; Awni, WM; Findlay, JW; Guay, DR; Halstenson, CE; Jones, EC; Matzke, GR; Opsahl, JA, 1988
)
1.45
" Peak concentration and AUC24 data for morphine glucuronide indicated that significant accumulation of this compound occurs upon multiple-dose administration."( Pharmacokinetics of codeine after single- and multiple-oral-dose administration to normal volunteers.
Abraham, PA; Awni, WM; Findlay, JW; Guay, DR; Halstenson, CE; Jones, EC; Matzke, GR; Opsahl, JA, 1987
)
0.6
" Mean values for single-dose pharmacokinetic parameters for SRC and IRC, respectively, were: Cmax of 217."( Human pharmacokinetic study of immediate-release (codeine phosphate) and sustained-release (codeine Contin) codeine.
Band, CJ; Band, PR; Besner, JG; Coldman, AJ; Deschamps, M, 1994
)
0.54
" Pharmacokinetic parameters were estimated by non-compartmental data analysis techniques."( Pharmacokinetic evaluation of two ibuprofen-codeine combinations.
Derendorf, H; Kaltenbach, ML; Mohammed, SS; Mullersman, G; Perrin, JH, 1994
)
0.55
" Referring to the pharmacokinetic parameters Cmax and tmax typical differences between oral and rectal formulations were observed."( Pharmacokinetics and drug input characteristics for a diclofenac-codeine phosphate combination following oral and rectal administration.
Hanses, A; Meiss, F; Mutschler, E; Spahn-Langguth, H, 1996
)
0.53
" Pharmacokinetic and pharmacodynamic analysis confirmed the findings of previous Phase I studies in healthy subjects."( A double-blind, randomized, parallel-group study of the pharmacokinetics and onset of action of Naprelan in patients following oral surgery.
Gaston, G, 1996
)
0.29
"To determine whether age-dependent pharmacokinetic and pharmacodynamic alterations account for a more pronounced response to benzodiazepines among elderly patients."( Pharmacokinetics and the pharmacodynamic action of midazolam in young and elderly patients undergoing tooth extraction.
Dilger, K; Klotz, U; Mikus, G; Platten, HP; Schweizer, E, 1998
)
0.3
"Elderly patients are more sensitive to the sedative action of midazolam than young patients, and the sensitivity is caused by age-dependent pharmacodynamic alterations."( Pharmacokinetics and the pharmacodynamic action of midazolam in young and elderly patients undergoing tooth extraction.
Dilger, K; Klotz, U; Mikus, G; Platten, HP; Schweizer, E, 1998
)
0.3
"This article outlines the main pharmacokinetic and toxicokinetic parameters of selected addicting compounds often being abused."( [Pharmacokinetic and toxicokinetic parameters of some drugs of abuse].
Panas, M, 2001
)
0.31
" In conclusion, glutethimide potentiates and prolongs the analgesic effect of codeine by a pharmacokinetic mechanism."( The study of codeine-gluthetimide pharmacokinetic interaction in rats.
Curea, E; Imre, S; Loghin, F; Popa, D, 2003
)
0.92
" A comparison is also presented between several methods based on animal pharmacokinetic data, using the same set of proprietary compounds, and it lends further support for the use of this method, as opposed to methods that require the gathering of pharmacokinetic data in laboratory animals."( Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
Gao, F; Lombardo, F; Obach, RS; Shalaeva, MY, 2004
)
0.32
" Large patient-to-patient variations in pharmacokinetic parameters occurred, although intraindividual variability was limited."( Inter- and intraindividual variabilities in pharmacokinetics of fentanyl after repeated 72-hour transdermal applications in cancer pain patients.
Bressolle, F; Caumette, L; Culine, S; Garcia, F; Pinguet, F; Poujol, S; Solassol, I, 2005
)
0.33
" Dihydrocodeine concentrations at the effect site were obtained by convolution of a first-order transfer function with the function describing the plasma concentration versus time courses, and miotic effects were related to effect-site concentrations by a sigmoidal pharmacodynamic model."( Pharmacokinetic-pharmacodynamic modeling of the miotic effects of dihydrocodeine in humans.
Lötsch, J; Schmidt, H, 2007
)
1.01
" The transfer half-life between plasma and effect site was 21."( Pharmacokinetic-pharmacodynamic modeling of the miotic effects of dihydrocodeine in humans.
Lötsch, J; Schmidt, H, 2007
)
0.57
" 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
" The validated LC-MS/MS method was applied to a pharmacokinetic study in which healthy Chinese volunteers each received a single oral dose of 30 mg codeine phosphate."( Rapid simultaneous determination of codeine and morphine in plasma using LC-ESI-MS/MS: application to a clinical pharmacokinetic study.
Deng, Y; Liao, Q; Pan, B; Xie, Z; Zhang, L, 2009
)
0.83
"Codeine is an important opioid anti-tussive agent whose short half-life (2."( Pharmacokinetics of a novel liquid controlled release codeine formulation.
Beubler, E; Dittrich, P; Haltmeyer, K; Roblegg, E; Zimmer, A, 2011
)
2.06
"Conventional mammillary models are frequently used for pharmacokinetic (PK) analysis when only blood or plasma data are available."( Applications of minimal physiologically-based pharmacokinetic models.
Cao, Y; Jusko, WJ, 2012
)
0.38
" The method was successfully applied to a pharmacokinetic study of codeine in healthy Mongolian Chinese volunteers after a 30 mg oral dose."( Simultaneous analysis of codeine and its active metabolites in human plasma using liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study after oral administration of codeine.
Bai, Y; Gu, J; Guo, T; Wu, X; Zhang, W, 2013
)
0.93
" A pharmacokinetic study was then carried out in three groups with CYP2D6*1/*1 (n=10), CYP2D6*1/*10 (n=10) and CYP2D6*10/*10 (n=9) genotypes by collecting serial blood samples for determination of plasma levels of codeine and its metabolites, morphine, morphine 3-glucuronide (M3G) and morphine 6-glucuronide (M6G) before and after a single 30-mg oral dose of codeine phosphate."( The impact of CYP2D6 polymorphisms on the pharmacokinetics of codeine and its metabolites in Mongolian Chinese subjects.
Guo, T; Lv, J; Wu, X; Yuan, L; Zuo, J, 2014
)
0.83
"No significant differences were observed in the pharmacokinetic parameters of codeine in the three genotype groups."( The impact of CYP2D6 polymorphisms on the pharmacokinetics of codeine and its metabolites in Mongolian Chinese subjects.
Guo, T; Lv, J; Wu, X; Yuan, L; Zuo, J, 2014
)
0.87
" We aimed to develop a codeine pharmacokinetic pathway model for codeine and its metabolites that incorporates the effects of genetic polymorphisms."( CYP2D6 phenotype-specific codeine population pharmacokinetics.
Boston, RC; Daly Linares, AL; Fudin, J; Linares, OA; Schiesser, WE, 2015
)
1.03
" The developed and validated method was successfully applied to a pharmacokinetic study of AAP (500mg) with DHC (20mg) capsule in Chinese healthy volunteers (N=20)."( Simultaneous determination of acetaminophen and dihydrocodeine in human plasma by UPLC-MS/MS: Its pharmacokinetic application.
Gao, P; Liu, Z; Lou, D; Qiu, X; Su, D; Zhang, NS, 2015
)
0.66
" The method herein described was superior to previous methods and was successfully applied to the pharmacokinetic study of DHC in healthy Chinese volunteers after oral administration."( UPLC-MS-MS Determination of Dihydrocodeine in Human Plasma and Its Application to a Pharmacokinetic Study.
Duan, YP; Li, W; Qiu, JF; Zhang, WM; Zhang, ZY, 2016
)
0.71
"The purpose of this study was to determine the pharmacokinetic and antinociceptive effects of an acetaminophen/codeine combination administered orally to six healthy greyhounds."( Pharmacokinetics and pharmacodynamics of oral acetaminophen in combination with codeine in healthy Greyhound dogs.
KuKanich, B, 2016
)
0.87
" However, this parameter is usually derived from a small database of human pharmacokinetic studies."( Refining the excretion factors of methadone and codeine for wastewater analysis - Combining data from pharmacokinetic and wastewater studies.
Bruno, R; Hall, W; Lai, FY; Mueller, JF; O'Brien, J; Prichard, J; Thai, PK; van Dyken, E, 2016
)
0.69
" In contrast to the rapid clearance of dihydrocodeine from blood in the 14-year-old girl (apparent half-life of 3 hours), the 1-month-old baby boy still had high serum concentrations of dihydrocodeine (400 nmol/L) and dihydromorphine (1."( Dihydrocodeine Overdoses in a Neonate and in a 14-year-old Girl Who Were Both Genotyped as Cytochrome P450 2D6*1/*10-*36: Comparing Developmental Ages and Drug Monitoring Data With the Results of Pharmacokinetic Modeling.
Fukuoka, T; Kondo, T; Shimizu, M; Tanaka, T; Yamazaki, H, 2018
)
1.19
" Pharmacokinetic studies in beagle dogs indicated that the optimized IB-CP SRCs had smaller individual differences and better reproducibility comparing with commercial available tablets."( Preparation, Characterization and Pharmacokinetics Evaluation of the Compound Capsules of Ibuprofen Enteric-Coated Sustained-Release Pellets and Codeine Phosphate Immediate-Release Pellets.
Dong, L; Pan, H; Pan, W; Yang, F; Yang, Y; Ye, M; Zhang, X; Zhu, Z, 2018
)
0.68
"To describe the pharmacokinetics and selected pharmacodynamic variables of codeine and its metabolites in Thoroughbred horses following a single oral administration."( Metabolism, pharmacokinetics and selected pharmacodynamic effects of codeine following a single oral administration to horses.
Finno, CJ; Gretler, SR; Kass, PH; Knych, HK; McKemie, DS, 2020
)
1.02
" Codeine was well tolerated based on pharmacodynamic variables and behavioral observations."( Metabolism, pharmacokinetics and selected pharmacodynamic effects of codeine following a single oral administration to horses.
Finno, CJ; Gretler, SR; Kass, PH; Knych, HK; McKemie, DS, 2020
)
1.7
" Blood samples were collected up to 72 hours post administration, codeine, codeine 6-glucuronide, norcodeine morphine, morphine 3-glucuronide and M6G concentrations determined by liquid chromatography- mass spectrometry and pharmacokinetic analysis performed."( Pharmacokinetics, adverse effects and effects on thermal nociception following administration of three doses of codeine to horses.
Gretler, SR; Kass, PH; Knych, HK; McKemie, DS; Stucker, K, 2022
)
1.17
" Plasma samples were collected, concentrations of drug and metabolites determined via liquid chromatography-mass spectrometry, and pharmacokinetic analyses were performed."( Pharmacokinetics and effects of codeine in combination with acetaminophen on thermal nociception in horses.
Kanarr, K; Kass, PH; Knych, HK; McKemie, DS; Tueshaus, T, 2023
)
1.19

Compound-Compound Interactions

The results indicate that TTS-F offers more effective pain relief than codeine/paracetamol, in combination with R/T. Drug-drug interactions can also affect the metabolism of codeine. The potentiation of dihydrocodeine-conditioned place preference was observed by combination with chlorpheniramine.

ExcerptReferenceRelevance
" The potentiation of dihydrocodeine-conditioned place preference was observed by combination with chlorpheniramine (0."( Drug interactions in the reinforcing effects of over-the-counter cough syrups.
Masukawa, Y; Misawa, M; Suzuki, T, 1990
)
0.57
"The objective of this study was to quantify the analgesic efficacy of paracetamol and its combination with codeine or caffeine through a systematic overview and meta-analysis of relevant randomized controlled trials (RCTs)."( Analgesic efficacy of paracetamol and its combination with codeine and caffeine in surgical pain--a meta-analysis.
Li Wan Po, A; Zhang, WY, 1996
)
0.75
"Pharmacokinetic drug-drug interactions with morphine, hydromorphone, and oxymorphone are reviewed in this column."( Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, part I.
Armstrong, SC; Cozza, KL,
)
0.39
"Pharmacokinetic drug-drug interactions with codeine, dihydrocodeine, hydrocodone, oxycodone, and buprenorphine are reviewed in this column."( Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, Part II.
Armstrong, SC; Cozza, KL,
)
0.65
"Only a relatively short immediate analgesic benefit could be demonstrated by a combination of IINB with spinal anaesthesia compared with IINB combined with general anaesthesia."( Analgesia and discharge following preincisional ilioinguinal and iliohypogastric nerve block combined with general or spinal anaesthesia for inguinal herniorrhaphy.
Permi, J; Rosenberg, PH; Toivonen, J, 2004
)
0.32
"Our objective was to investigate the frequency of potential drug-drug interactions between the prodrugs losartan, codeine, and tramadol and drugs known to inhibit their activation in hospitalized patients."( Drug interactions with the potential to prevent prodrug activation as a common source of irrational prescribing in hospital inpatients.
Laine, K; Tirkkonen, T, 2004
)
0.53
" The results therefore indicate that TTS-F offers more effective pain relief than codeine/paracetamol, in combination with R/T, in patients with metastatic bone pain, obtaining complete treatment satisfaction matched by improvements in their QoL."( Comparison of transdermal fentanyl with codeine/paracetamol, in combination with radiotherapy, for the management of metastatic bone pain.
Katsouda, E; Kouloulias, V; Kouvaris, J; Mystakidou, K; Tsiatas, M; Vlahos, L,
)
0.62
" Thus, in vitro-in vivo extrapolation approaches were used to identify potential drug-drug interactions arising from inhibition of COD glucuronidation in humans."( In vitro-in vivo extrapolation predicts drug-drug interactions arising from inhibition of codeine glucuronidation by dextropropoxyphene, fluconazole, ketoconazole, and methadone in humans.
Elliot, DJ; Janchawee, B; Miners, JO; Raungrut, P; Somogyi, AA; Uchaipichat, V, 2010
)
0.58
"We present a database of prescription drugs and international normalized ratio (INR) data and the applied methodology for its use to assess drug-drug interactions with vitamin K antagonists (VKAs)."( Pharmacoepidemiological assessment of drug interactions with vitamin K antagonists.
dePont Christensen, R; Gagne, JJ; Hallas, J; Larsen, TB; Pottegård, A; Wang, SV, 2014
)
0.4
"Auricular point sticking before operation combined with conventional western medicine with oral administration for preventing and treating postoperative complications of external excision and internal ligation on mixed hemorrhoid achieves positive and reliable efficacy."( [Clinical observation of auricular point sticking combined with western medicine for preventing and treating postoperative complications of external excision and internal ligation on mixed hemorrhoid].
Li, J; Long, Q; Wen, Y, 2015
)
0.42
"To assess whether a "drugome-wide" screen with case-crossover design is a feasible approach for identifying candidate drugs and drug-drug interactions."( Screening approach for identifying candidate drugs and drug-drug interactions related to hip fracture risk in persons with Alzheimer disease.
Hartikainen, S; Koponen, M; Lavikainen, P; Paananen, J; Taipale, H; Tanskanen, A; Tiihonen, J; Tolppanen, AM, 2017
)
0.46
"Case-crossover analysis is a potential approach for identifying candidate drugs and drug-drug interactions associated with adverse events as it implicitly controls for fixed confounders."( Screening approach for identifying candidate drugs and drug-drug interactions related to hip fracture risk in persons with Alzheimer disease.
Hartikainen, S; Koponen, M; Lavikainen, P; Paananen, J; Taipale, H; Tanskanen, A; Tiihonen, J; Tolppanen, AM, 2017
)
0.46
" In this paper, a novel strategy for quality assessment of PPCE, systematic quantified fingerprint method (SQFM) combined with quantitative analysis of multi-components by a single marker (QAMS) method, was developed and validated."( Quality evaluation of powdered poppy capsule extractive by systematic quantified fingerprint method combined with quantitative analysis of multi-components by single marker method.
Guo, Y; Sun, G; Wang, Y; Yu, Y, 2020
)
0.56
" Drug-drug interactions can also affect the metabolism of codeine."( A software tool to adjust codeine dose based on CYP2D6 gene-pair polymorphisms and drug-drug interactions.
Nakad, Z; Saab, Y, 2023
)
1.45

Bioavailability

Bioavailability of codeine using the dosed feed route increased with dose, varying from 10% to 25%. The relative codeine bioavailability in these groups was 54. Liquid controlled release codeine formulations such as an older Codipertussin(®) formulation, achieved an equivalent bioavailability when administered every 12 h.

ExcerptReferenceRelevance
" intramuscular bioavailability of codeine in man."( Analgesic studies of codeine and oxycodone in patients with cancer. I. Comparisons of oral with intramuscular codeine and of oral with intramuscular oxycodone.
Beaver, WT; Houde, RW; Rogers, A; Wallenstein, SL, 1978
)
0.86
" The assay was developed for use in bioavailability studies of therapeutic doses of oxycodone."( Quantitative GLC determination of oxycodone in human plasma.
Renzi, NL; Tam, JN, 1979
)
0.26
"Radioimmunoassay (RIA) was used to determine several pharmacokinetic parameters of codeine in man, including the relative bioavailability after oral and intramuscular administration."( Codeine kinetics as determined by radioimmunoassay.
Butz, RF; Findlay, JW; Welch, RM, 1977
)
1.92
" It was developed for use in bioavailability studies of therapeutic doses of codeine sulfate."( Gas-chromatographic measurement of codeine and norcodeine in human plasma.
Brunson, MK; Nash, JF, 1975
)
0.76
" The assumed oral bioavailability ratios were 44% (group 1, first 10 patients) and 33% (group 2, last 10 patients) for morphine and 66% (group 1) and 50% (group 2) for oxycodone hydrochloride, respectively."( Morphine and oxycodone hydrochloride in the management of cancer pain.
Kalso, E; Vainio, A, 1990
)
0.28
"25 mg), codeine phosphate (8 mg) and paracetamol (500 mg) had any effect on the bioavailability of the analgesics."( The relative bioavailability of paracetamol and codeine after oral administration of a combination of buclizine, paracetamol and codeine, with or without docusate, and of paracetamol alone in healthy volunteers.
Johnson, ES; Merrington, D; Oliver, W; Persaud, N, 1985
)
0.96
" The method provides high sensitivity and selectivity and has been used successfully in bioavailability studies."( Determination of opiates and other basic drugs by high-performance liquid chromatography with electrochemical detection.
Band, C; Besner, JG; Caillé, G; Rondeau, JJ; Stewart, J; Varin, F; Yamlahi, L, 1989
)
0.28
" Individual pharmacokinetic parameters were calculated according to standard procedures and the magnitude and rate of bioavailability were tested using a 95% confidence internal approach."( Bioavailability study of fosfosal and codeine administered alone or in combination.
Forn, J; Gich, I; Jané, F; Mis, R; Ramis, J; Torrent, J, 1989
)
0.55
" These methods have been used to compare the bioavailability in four subjects of a controlled-release formulation of dihydrocodeine bitartrate (equivalent to 90 mg of base) with that of a solution (equivalent to 3 x 30 mg of base)."( Two assays for dihydrocodeine in plasma and in urine and their use to determine the bioavailability of a controlled-release product.
Cowan, DA; Noormohammadi, A; Woffendin, G, 1988
)
0.8
"Eight healthy male volunteers took part in this study to determine the relative bioavailability of Treuphadol oblong tablets (500 mg paracetamol), Treuphadol Plus oblong tablets (500 mg paracetamol, 30 mg codeine phosphate) and Treuphadol suppositories (750 mg paracetamol) against commercial tablets (500 mg paracetamol)."( [Relative bioavailability of paracetamol from tablets and suppositories as well as of paracetamol and codeine in a combination tablet].
Barkworth, MF; Birkenfeld, A; Cierpka, H; Dyde, CJ; Klein, G; Rehm, KD; Töberich, H, 1986
)
0.67
" Bioavailability data for paracetamol derived from the results were similar to those reported by other workers who studied suppositories containing paracetamol as the only active ingredient."( The relative bioavailability of paracetamol after rectal administration of suppositories containing a mixture of paracetamol, codeine phosphate and buclizine hydrochloride in healthy volunteers.
Burgess, HA; Merrington, DM; Oliver, WJ; Rogers, HJ; Thomson, A, 1985
)
0.48
" The mean absolute bioavailability of acetylsalicylic acid was 68% after oral application and 60% after rectal application."( [The bioavailability of combination preparations of acetylsalicylic acid and codeine phosphate].
Altmayer, P; Cattarius-Korb, S; Krüger, B; Lang, E; Mutschler, E; Sörgel, F; Spahn, H, 1985
)
0.5
" The compound appeared to be well absorbed in the three species."( Disposition and metabolism of codorphone in the rat, dog, and man.
Evans, JV; Helms, RJ; Leeling, JL; Ryerson, BA,
)
0.13
" A plasma concentration-time curve from a subject administered a single oral dose of hydromorphone demonstrates the usefulness of the assay in monitoring drug levels in a bioavailability study."( Radioimmunoassay of hydromorphone and hydrocodone in human plasma.
Honigberg, IL; Stewart, JT, 1980
)
0.26
" Bioavailability of dextromethorphan tablets was comparable to syrup."( Dextromethorphan and codeine: comparison of plasma kinetics and antitussive effects.
Aylward, M; Davies, DE; Leideman, T; Maddock, J; Protheroe, DA, 1984
)
0.59
" The bioavailability of meprobamate administered rectally to human volunteers as the marketed preparations DoloVisano Suppositories and Dolo-Visano Suppositories sine codeino, is similar to that observed following oral administration."( The pharmacokinetics of meprobamate following its oral and rectal administration as a series of combinations with diphenhydramine, acetylsalicylic acid, codeine and pentaerythritol tetranitrate.
Aylott, RI; Draffan, GH; Gilbert, JD; Sögtrop, HH, 1984
)
0.47
" From the AUC, the mean bioavailability of orally administered drug was 21% (range 12-34%)."( Pharmacokinetics of intravenous and oral dihydrocodeine and its acid metabolites.
Rawlins, MD; Rowell, FJ; Seymour, RA, 1983
)
0.52
" The relative bioavailability from the two forms of application was also computed."( [Bioavailability of codeine and paracetamol in a combination preparation following oral and rectal administration].
Kummer, M; Mehlhaus, N, 1984
)
0.59
"The bioavailability of codeine and extent of its transformation to morphine were stated in 12 smoking and 11 nonsmoking subjects after single doses 60 mg IM codeine and 60 mg codeine sulfate orally, given 1 wk apart."( Codeine disposition in smokers and nonsmokers.
Bustrack, JA; Butz, RF; Findlay, JW; Hull, JH; Jones, EC; Rogers, JF; Welch, RM, 1982
)
2.02
" We conclude (a) that therapeutic doses of codeine increase net intestinal absorption (and thereby reduce stool volume) by increasing the contact time of luminal fluid with mucosal cells, not by increasing the rate of absorption by the mucosal cells; and (b) that endogenous opiates do not regulate intestinal absorption in humans."( Studies of the mechanism of the antidiarrheal effect of codeine.
Davis, GR; Fordtran, JS; Morawski, SG; Santa Ana, CA; Schiller, LR, 1982
)
0.77
" The relative codeine bioavailability in these groups was 54."( An evaluation of the effects of smoking on codeine pharmacokinetics and bioavailability in normal human volunteers.
Bustrack, JA; Butz, RF; Findlay, JW; Hull, JH; Rogers, JF; Welch, RM, 1982
)
0.89
" The relative bioavailability of the [3H]-codeine phosphate released from the capsule and from the two tablets was shown to be the same comparing the areas under the plasma level curves."( [Plasma levels and renal excretion of [3H]-codeine phosphate in humans receiving tablets or depot capsules (author's transl)].
Bechtel, WD; Sinterhauf, K, 1980
)
0.79
" These results indicate comparable bioavailability between both formulations with SRC providing delayed peak plasma levels."( Human pharmacokinetic study of immediate-release (codeine phosphate) and sustained-release (codeine Contin) codeine.
Band, CJ; Band, PR; Besner, JG; Coldman, AJ; Deschamps, M, 1994
)
0.54
" Bioavailability of codeine using the dosed feed route increased with dose, varying from 10% to 25%, which was somewhat higher than the previously reported approximately 8% bioavailability using the gavage route."( Codeine toxicokinetics in rats during a two-year dosed feed study.
Barnes, ER; Dunnick, JK; Findlay, JW; Yuan, J,
)
1.9
" The results obtained show a similar extent of diclofenac and codeine bioavailability for both administration routes, but the rate of drug input was lower for the suppositories."( Pharmacokinetics and drug input characteristics for a diclofenac-codeine phosphate combination following oral and rectal administration.
Hanses, A; Meiss, F; Mutschler, E; Spahn-Langguth, H, 1996
)
0.77
"The study objective was to compare the bioavailability of codeine and ibuprofen after oral administration of the two drugs alone or in association."( Comparative bioavailability study of codeine and ibuprofen after administration of the two products alone or in association to 24 healthy volunteers.
Delarue, A; Duchene, P; Gleizes, S; Hirt, P; Houin, G; Laneury, JP; Molinier, P,
)
0.65
"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 plasma concentrations of codeine were measured to eliminate differences in the bioavailability and clearance of codeine as factors that might account for the differences in codeine hair concentrations."( The effect of hair color on the incorporation of codeine into human hair.
Augsburger, MP; Borges, CR; Krueger, GG; Mizuno, A; O'Neal, C; Rollins, DE; Slawson, MH; Wilkins, DG,
)
0.67
" A mean bioavailability of 78% was estimated; the total clearance averaged 41 L/h."( Inter- and intraindividual variabilities in pharmacokinetics of fentanyl after repeated 72-hour transdermal applications in cancer pain patients.
Bressolle, F; Caumette, L; Culine, S; Garcia, F; Pinguet, F; Poujol, S; Solassol, I, 2005
)
0.33
" 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
"Failure to recognize the impact of various situations described throughout this work, including the bioavailability due to loss of oral route, due to pharmacokinetics and pharmacodynamics of the various drugs, either in the context of the impaired metabolism or excretion, or in due to pharmacological interactions, conditions a serious risk of subtreatment of pain and consequent impact in terms of quality of life."( [Opioids for Cancer Pain and its Use under Particular Conditions: A Narrative Review].
Brás, M; Fragoso, M; Vieira, C, 2019
)
0.51

Dosage Studied

A new HPLC method for separation and determination of impurities in paracetamol, codeine phosphate hemihydrate and pitophenone hydrochloride was developed and validated. Codeine toxicokinetics in F344 rats of both sexes were determined during a 2-year chronic toxicology study.

ExcerptRelevanceReference
" In the oxycodone group, only two patients (12%) needed maximal dosage (6 x 4 mg), one of them requiring 32 mg of oxycodone."( Comparison of the analgesic dose-effect relationships of nefopam and oxycodone in postoperative pain.
Leander, P; Tammisto, T; Tigerstedt, I, 1979
)
0.26
" These results suggest that codeine phosphate has a beneficial effect on ileostomy function, reducing the loss of water and electrolytes, while Lomotil has a similar but less effective action in the dosage tested."( Effect of codeine phosphate, Lomotil, and Isogel on iileostomy function.
Newton, CR, 1978
)
0.95
"The quantitative determinations of codeine phosphate, guaifenesin, pheniramine maleate, phenylpropanolamine hydrochloride, and pyrilamine maleate in a liquid dosage form are described."( Quantitative determinations of codeine phosphate, guaifenesin, pheniramine maleate, phenylpropanolamine hydrochloride, and pyrilamine maleate in an expectorant by high-pressure liquid chromatography.
Ghanekar, AG; Gupta, VD, 1977
)
0.82
" The analgesia dose-response curves for the surrogate pairs, nalodeine-nalorphine and codeine-morphine, were parallel but had significantly different slopes."( A comparative study of the analgesic and respiratory effects of N-allylnorcodeine (nalodeine), nalorphine, codeine and morphine.
Elliott, HW; Rundlett Beyer, J, 1976
)
0.71
" The very shallow dose-response curves for flurbiprofen compared with acetylsalicylic acid, especially in the mouse and the rat test systems, are not due to an unreliable or abnormal absorption, which suggests that in these species the mode of action of flurbiprofen is not identical with that of acetylsalicylic acid."( Some biological properties of flurbiprofen, an anti-inflammatory, analgesic and antipyretic agent.
Adams, SS; McCullough, KF; Nicholson, JS, 1975
)
0.25
"Derivatization of the alkaloids cephaeline, codeine, emetine, ephedrine, morphine, narcotine and others with dansyl chloride has been studied with the aim of developing a sensitive and specific liquid chromatographic method for these substances in complex pharmaceutical dosage forms."( Liquid chromatography of dansyl derivatives of some alkaloids and the application to the analysis of pharmaceuticals.
Frei, RW; Santi, W; Thomas, M, 1976
)
0.52
" The last dosage was repeated every 12 hrs for 4 times more."( [The epidemiology of adverse reactions to nonsteroidal anti-inflammatory drugs. Nimesulide is tolerated by patients with adverse reactions to NSAIDs and modulates in man the skin response to histamine and codeine].
Altucci, P; Astarita, C; Ferrara, AM; Franzese, A; Raucci, G; Scala, G; Sproviero, S, 1992
)
0.47
" Tolerance in terms of withdrawals or side-effect profile did not appear to the dosage of each preparation administered."( The efficacy and tolerability of controlled-release dihydrocodeine tablets and combination dextropropoxyphene/paracetamol tablets in patients with severe osteoarthritis of the hips.
Costello, F; Eves, MJ; James, IG; Lloyd, RS; Miller, AJ, 1992
)
0.53
" This trial design (crossover with multiple dosing in outpatients) is a sensitive way of testing for analgesia, and is potentially more predictive of adverse effect problems than single-dose studies."( A multiple dose comparison of combinations of ibuprofen and codeine and paracetamol, codeine and caffeine after third molar surgery.
Carroll, D; Guest, P; Juniper, RP; McQuay, HJ; Moore, RA, 1992
)
0.53
"Timed-pregnant LVG Syrian hamsters and Swiss CD-1 mice were dosed orally twice daily (b."( Codeine: developmental toxicity in hamsters and mice.
George, JD; Kimmel, CA; Marr, MC; Morrissey, RE; Price, CJ; Sleet, RB; Williams, J, 1991
)
1.72
" Flurbiprofen in 50 mg and 100 mg dosages demonstrated effective analgesic activity with the 100 mg dosage being at least as effective as the acetaminophen/codeine combination."( The analgesic efficacy of flurbiprofen compared to acetaminophen with codeine.
Cooper, SA; Kupperman, A, 1991
)
0.71
" Two moderate respiratory depressions occurred in 1989 due to error in dosage with no consequence for the child."( [Intraoperative and postoperative analgesia in pediatric surgery. 1 years' experience].
Charles-Guillard, S; Heloury, Y; Meignier, M; Pannier, M; Ricard, P; Rogez, JM; Zaouter, M, 1990
)
0.28
" On the other hand, concurrent dosing of dihydrocodeine (2 mg/kg, IP) and a mixture (SC) of methylephedrine (4 mg/kg), caffeine (4 mg/kg) and chlorpheniramine (0."( Drug interactions in the reinforcing effects of over-the-counter cough syrups.
Masukawa, Y; Misawa, M; Suzuki, T, 1990
)
0.53
" morphine dose-response line was shown to be displaced progressively to the right with decreasing maximal effect (i."( Modulation of the potency and efficacy of mu-mediated antinociception by delta agonists in the mouse.
Mosberg, HI; Porreca, F; Qi, JN, 1990
)
0.28
" To verify that the dosage of codeine administered was sufficient to produce analgesia, we also determined the effect of this dosage on the time that subjects could tolerate immersion of one hand in ice water."( Effect of codeine on the sensations elicited by loaded breathing.
Altose, M; Bark, H; Chapman, K; Clary, S; Dimarco, A; Supinski, G, 1990
)
0.97
"8 ml per min) was significantly lower than that in the young (137 ml per min), and there was a significant correlation between the half-life at single dosing and the blood urea concentration."( The effect of ageing on the pharmacokinetics of dihydrocodeine.
Castleden, CM; Davies, KN; Jagger, C; McBurney, A, 1989
)
0.52
" The 30% increase in analgesic effect may be of clinical benefit, and this trial design, cross-over with multiple dosing in out-patients, may be a sensitive test for analgesics, potentially more predictive of side-effect problems than single-dose studies."( Codeine 20 mg increases pain relief from ibuprofen 400 mg after third molar surgery. A repeat-dosing comparison of ibuprofen and an ibuprofen-codeine combination.
Carroll, D; Juniper, RP; McQuay, HJ; Moore, RA; Watts, PG, 1989
)
1.72
" Systemic dosing of opiates is therefore required to reduce the cough reflex, whereas inhaled opiates may reduce the increase in Rrs after inhaled capsaicin."( Effect of inhaled and systemic opiates on responses to inhaled capsaicin in humans.
Choudry, NB; Fuller, RW; Karlsson, JA; Pride, NB, 1988
)
0.27
" Blood and saliva samples and all urine were collected over 168 h after each dosage administration."( Pharmacokinetics of pholcodine in healthy volunteers: single and chronic dosing studies.
Bochner, F; Chen, ZR; Somogyi, A, 1988
)
0.27
" Adjustment of dosage regimen may be required in some patients with uremia receiving multiple-dose codeine therapy."( Pharmacokinetics and pharmacodynamics of codeine in end-stage renal disease.
Abraham, PA; Awni, WM; Findlay, JW; Guay, DR; Halstenson, CE; Jones, EC; Matzke, GR; Opsahl, JA, 1988
)
0.76
" However, accumulation of morphine during multiple dosing was significant (AUC24 = 102 +/- 33 ng/mL/hr after single dose versus 212 +/- 118 ng/mL/hr after the last multiple dose)."( Pharmacokinetics of codeine after single- and multiple-oral-dose administration to normal volunteers.
Abraham, PA; Awni, WM; Findlay, JW; Guay, DR; Halstenson, CE; Jones, EC; Matzke, GR; Opsahl, JA, 1987
)
0.6
" The dosage was two tablets taken as early as possible in the acute attack."( A treatment for the acute migraine attack.
Adam, EI,
)
0.13
" ED50 values were derived from the dose-response lines."( Intrathecal injection of codeine, buprenorphine, tilidine, tramadol and nefopam depresses the tail-flick response in rats.
Bernatzky, G; Jurna, I, 1986
)
0.57
"This paper evaluates the dose-response relationship of several doses of fenoprofen calcium, between 12."( Dose response to fenoprofen calcium using placebo and codeine as controls.
Gruber, CM; Offen, WW, 1985
)
0.52
" In the multiple dosing phase, zomepirac was statistically better than dihydrocodeine."( Zomepirac, dihydrocodeine and placebo compared in postoperative pain after day-case surgery. The relationship between the effects of single and multiple doses.
Bullingham, RE; Carroll, D; Collin, J; Evans, PJ; Lloyd, JW; McQuay, HJ; Moore, RA; O'Sullivan, G, 1985
)
0.83
" Dose-response studies revealed that the inhibition of mast cell-mediated wealing required a certain cumulative threshold dose of UVR (about 35 J/cm2 UVA + 20 mJ/cm2 UVB)."( UV suppression of mast cell-mediated wealing in human skin.
Gollhausen, R; Kaidbey, K; Schechter, N, 1985
)
0.27
" The absence of any effects of a 2-mg/kg dose of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol and the severe side effects produced by 10 mg/kg prevented determination of its dose-response relationship."( Shock titration in the rhesus monkey: effects of opiate and nonopiate analgesics.
Bloss, JL; Hammond, DL, 1985
)
0.27
" Codeine and paracetamol tested individually were effective only at relatively high dosage and, like the combination, their analgesic effects were greater after rectal administration and more clearly dose-dependent than after oral administration."( Acute toxicity and analgesic action of a combination of buclizine, codeine and paracetamol ('Migraleve') in tablet and suppository form in rats.
Behrendt, WA; Cserepes, J, 1985
)
1.42
" 24 had received pentazocine after discharge; two required an increase in dosage and four expressed a preference for pentazocine."( Medicines evaluation and monitoring group: central nervous system effects of pentazocine.
Campbell, C; Davidson, JF; Gallon, SC; Henney, E; McAllion, S; Moir, DC; Wood, AJ, 1974
)
0.25
" Rats were dosed continuously with morphine hydrochloride by giving a daily dose through tubes connected to small, subcutaneously implanted reservoirs."( An implanted reservoir of morphine solution for rapid induction of physical dependence in rats.
Goode, PG, 1971
)
0.25
" To illustrate the usefulness of this methodology, a urine sample obtained from a dog that had been dosed with codorphone was analyzed by gas chromatography mass spectrometry, and the metabolites were identified by comparison to the mass spectra of the synthetic derivatives."( Methodology for the identification of the urinary metabolites of the analgesic-narcotic antagonist, codorphone, by gas chromatography mass spectrometry.
Evans, JV; Helms, RJ; Leeling, JL, 1982
)
0.26
" Adverse reactions occurred more often with higher doses of morphine and codeine; the dose-response relationship could not be evaluated for the other three drugs."( Clinical effects of parenteral narcotics in hospitalized medical patients.
Miller, RR, 1980
)
0.49
" A clinical dose-response relationship has been established, and time-effect curves indicate that the total threshold-raising effect depends on dosage frequency."( Review of the comparative analgesic efficacy of salicylates, acetaminophen, and pyrazolones.
Mehlisch, DR, 1983
)
0.27
" Interpretation of single dose studies with extrapolation to repeated dosing in the practice setting is difficult."( An appraisal of codeine as an analgesic: single-dose analysis.
Honig, S; Murray, KA,
)
0.48
" The first study involved 90 patients in a double-blind comparative trial of glaucine and codeine: both treatments were administered as a syrup at a dosage of 30 mg 3-times daily for 7 days."( Efficacy and tolerability of glaucine as an antitussive agent.
Criscuolo, D; Dieterich, HA; Gastpar, H, 1984
)
0.49
" It is suggested that this method of testing the effects of an antitussive on such a dose-response curve may be a useful one."( An electromyographic method of objectively assessing cough intensity and use of the method to assess effects of codeine on the dose-response curve to citric acid.
Apps, MC; Burke, CA; Cox, ID; Empey, DW; Hughes, DT; Osman, RC; Wallis, PJ, 1984
)
0.48
"Plasma kinetics of dextromethorphan (as dextrorphan ) and codeine were investigated after acute oral doses in 8 patients with pathological cough; after which the patients participated in an acute dose-response study of the antitussive effects of each drug administered as syrups."( Dextromethorphan and codeine: comparison of plasma kinetics and antitussive effects.
Aylward, M; Davies, DE; Leideman, T; Maddock, J; Protheroe, DA, 1984
)
0.83
" Although morphine (ID50 = 4 micrograms) was a very potent analgesic when given intracerebroventricularly, very shallow dose-response curves were obtained with the other substances which promoted less than 30% of inhibition at doses up to 250 micrograms."( The peripheral analgesic effect of morphine, codeine, pentazocine and d-propoxyphene.
Ferreira, SH; Lorenzetti, BB; Molina, N; Vettore, O, 1983
)
0.53
"Rectal absorption of codeine phosphate from various dosage forms was studied in man."( Rectal versus oral absorption of codeine phosphate in man.
Grasmeijer, G; Meijer, DK; Moolenaar, F; Visser, J,
)
0.73
" A statiscally significant dose-response relationship was obtained between the supplementary doses of codeine and analgesic efficacy."( Paracetamol plus supplementary doses of codeine. An analgesic study of repeated doses.
Ahlström, U; Bångens, S; Hellem, S; Johansson, G; Jönsson, E; Nordh, PG; Persson, G; Quiding, H, 1982
)
0.75
"The dissolution rate constants of dihydrocodein in two retard drug dosage forms based on synthetic ion exchange resin were determined with four dissolution methods."( [Investigations in Bioavailability of resinates as peroral retard drug dosage forms. Part 1: Pharmaceutical availability of dihydrocodein-resinates (author's transl)].
Glaubitz, H; Mühlenbruch, B; Strauss, H, 1982
)
0.26
" Sulfur dioxide was packed into aerosol cans equipped with a 75 microliter dosage nozzle."( An improvement to the use of sulfur dioxide to induce cough in experimental animals.
Airaksinen, MM; Karttunen, P; Koskiniemi, J, 1982
)
0.26
"Studies were conducted on postpartum and postoperative patients to estimate the dose-response line of fenoprofen and to contrast it with codeine and placebo."( Fenoprofen and codeine analgesia.
Laska, EM; Sunshine, A, 1981
)
0.82
" The method is currently being used in dose-response disposition studies to quantitate codeine and its major metabolites in human subjects."( Quantitative determination of codeine and its major metabolites in human hair by gas chromatography-positive ion chemical ionization mass spectrometry: a clinical application.
Foltz, R; Haughey, H; Krueger, G; Rollins, DE; Seaman, J; Wilkins, D, 1995
)
0.8
" After repeated dosing (12-15 days), moguisteine did not induce tolerance in either guinea-pigs or dogs."( Moguisteine: a novel peripheral non-narcotic antitussive drug.
Borghi, A; Ceserani, R; Dalla Rosa, C; Gallico, L; Tognella, S, 1994
)
0.29
"The improved pain control provided by regular dosing of opioid analgesics in patients with severe cancer pain has been well established."( The dose-response relationship of controlled-release codeine (Codeine Contin) in chronic cancer pain.
Chary, S; Darke, AC; Goughnour, BR; Harsanyi, Z; Moulin, DE; Thorpe, WR, 1994
)
0.54
" With the use of the tail flick model, dose-response curves were constructed to codeine, morphine, oxycodone and oxymorphone (the O-demethylated metabolite of oxycodone) in both rat strains."( The influence of pharmacogenetics on opioid analgesia: studies with codeine and oxycodone in the Sprague-Dawley/Dark Agouti rat model.
Bochner, F; Cleary, J; Mikus, G; Somogyi, A, 1994
)
0.75
" In the physical dependence test, nefiracetam and codeine phosphate were administered to rats mixed with food for 43 days in a gradually increasing dosage schedule, followed by feeding a drug-free normal diet to detect signs of withdrawal."( Drug dependence study of the new cognition-enhancing agent nefiracetam in rats.
Akiyama, Y; Fujikawa, K; Takayama, S, 1994
)
0.54
" The results suggest that ibuprofen and codeine can be given safely in a single oral dosage form."( Pharmacokinetic evaluation of two ibuprofen-codeine combinations.
Derendorf, H; Kaltenbach, ML; Mohammed, SS; Mullersman, G; Perrin, JH, 1994
)
0.82
"Randomized, double-blind, parallel, dose-response study."( Picenadol in a large multicenter dental pain study.
Brunelle, RL; Cooper, SA; Desjardins, PJ; Gallegos, LT; Gaston, GW; George, RE; Goldstein, DJ; Jeffers, GE; Reynolds, DC,
)
0.13
" No addiction to the drugs, and in particular no need of a dosage increase was observed during the whole period of 18 months."( [Restless legs syndrome. Report of experience].
Grandjean, P, 1993
)
0.29
" Analysis of some commercial dosage forms containing one of these congeners showed good recovery with sufficient accuracy and precision."( Ion-pair reversed-phase liquid chromatographic identification and quantitation of papaverine congeners.
Girgis, EH, 1993
)
0.29
" The experimental group received a standard dosage of oral postoperative corticosteroids."( Arthroscopy of the knee. Ten-day pain profiles and corticosteroids.
Highgenboten, CL; Jackson, AW; Meske, NB,
)
0.13
"The purpose of the study was to compare histamine release in human skin by codeine, delivered by an intraprobe drug delivery system (IPD) and intracutaneous injections (ICT), with respect to dose-response relations, kinetics of histamine appearance and decay, correlations between histamine release and skin responses, and reproducibility."( Codeine-induced histamine release in intact human skin monitored by skin microdialysis technique: comparison of intradermal injections with an atraumatic intraprobe drug delivery system.
Nielsen, HJ; Petersen, LJ; Skov, PS, 1995
)
1.96
" Airway hyperresponsiveness was evidenced by significant shifts to the left of dose-response curves for intravenous acetylcholine (ACh) without a change in maximum responses to ACh."( The tachykinin NK2 receptor antagonist SR 48968 inhibits citric acid-induced airway hyperresponsiveness in guinea pigs.
Advenier, C; Emonds-Alt, X; Girard, V; Yavo, JC, 1996
)
0.29
" Fourteen days after beginning the dosing protocol, hair was collected and analyzed for codeine, and its metabolite, morphine, by positive-ion chemical ionization GC/ion-trap MS."( Incorporation of codeine and metabolites into hair. Role of pigmentation.
Cone, EJ; Gygi, SP; Joseph, RE; Rollins, DE; Wilkins, DG, 1996
)
0.86
" This seems to be caused by a slow release from the dosage form or dissolution of the drugs, which is confirmed by a longer MITtot compared to the MRTsys in most of the volunteers."( Pharmacokinetics and drug input characteristics for a diclofenac-codeine phosphate combination following oral and rectal administration.
Hanses, A; Meiss, F; Mutschler, E; Spahn-Langguth, H, 1996
)
0.53
" At various times during and after the dosing protocol, approximately 50 mg of hair was shaved from a different area of the animals' backs and analyzed for codeine and morphine concentrations by ion-trap gas chromatography-mass spectrometry."( Distribution of codeine and morphine into rat hair after long-term daily dosing with codeine.
Gygi, SP; Rollins, DE; Wilkins, DG, 1995
)
0.83
"05) dose-response relationship."( Analgesic efficacy of paracetamol and its combination with codeine and caffeine in surgical pain--a meta-analysis.
Li Wan Po, A; Zhang, WY, 1996
)
0.54
") opioid analgesic administration (PCA) with fixed schedule and dosage oral/rectal administration of naproxen, and opioid analgesics intramuscularly/orally as needed (i."( A comparison of patient-controlled and fixed schedule analgesia after orthognathic surgery.
Finley, GA; McGrath, P; Multari, J; Precious, DS, 1997
)
0.3
" Hair was collected from the back 14 days after beginning the 5-day dosing protocol and analyzed by gas chromatography/mass spectrometry (GC/MS) for codeine and phenobarbital."( A comparison of phenobarbital and codeine incorporation into pigmented and nonpigmented rat hair.
Gygi, SP; Rollins, DE; Wilkins, DG, 1997
)
0.78
" Tramadol showed a dose-response for analgesia in both postsurgical and dental pain patients."( Single-patient data meta-analysis of 3453 postoperative patients: oral tramadol versus placebo, codeine and combination analgesics.
McQuay, JH; Moore, AR, 1997
)
0.52
" The same dosing sequence was repeated in week 8 with doubled (x 2) doses."( Drug testing with alternative matrices I. Pharmacological effects and disposition of cocaine and codeine in plasma, sebum, and stratum corneum.
Cone, EJ; Joseph, RE; Ohuoha, C; Oyler, JM; Wstadik, AT,
)
0.35
" This conclusion must however, be confirmed with repeated dosing in patients with pain."( The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. A cross-over study with extensive and quinidine-induced poor metabolizers.
Hufschmid, E; Thormann, W; Wilder-Smith, CH, 1998
)
0.54
" Medical records were reviewed to determine reasons for opioid dosage escalations."( Codeine and oxycodone use in patients with chronic rheumatic disease pain.
Mahowald, ML; Woods, SR; Ytterberg, SR, 1998
)
1.74
" Because of similar metabolic degradation, calculation of the time-dependent ratio of the concentration of morphine and its glucuronide metabolites in blood or serum allows a rough estimation of increased dosage and of time elapsed since the last application."( Formation and clearance of active and inactive metabolites of opiates in humans.
Aderjan, RE; Skopp, G, 1998
)
0.3
" A secondary goal was to determine the accuracy of Drug Recognition Examiners (DREs) in detecting if subjects were dosed with these drugs."( Laboratory validation study of drug evaluation and classification program: alprazolam, d-amphetamine, codeine, and marijuana.
Crouch, DJ; Heishman, SJ; Singleton, EG, 1998
)
0.52
" Dose-response relationships show that higher doses of ibuprofen may be particularly effective."( Postoperative analgesia and vomiting, with special reference to day-case surgery: a systematic review.
McQuay, HJ; Moore, RA, 1998
)
0.3
" Clinical applications are rare because of the lack of dose-response relationships in the studies performed to date, and questions remain regarding the mechanisms of drug incorporation into hair."( Codeine concentration in hair after oral administration is dependent on melanin content.
Ahlner, J; Förstberg-Peterson, S; Kågedal, B; Kronstrand, R; Larson, G, 1999
)
1.75
" The same dosing sequence was repeated in week 8 with doubled doses (high-dose week)."( Drug testing with alternative matrices II. Mechanisms of cocaine and codeine deposition in hair.
Cone, EJ; Höld, KM; Joseph, RE; Rollins, DE; Wilkins, DG, 1999
)
0.54
" Sweat specimens were collected for 30 min at various times following administration of cocaine or codeine in controlled dosing studies."( Sweat testing for cocaine, codeine and metabolites by gas chromatography-mass spectrometry.
Cone, EJ; Huestis, MA; Joseph, RE; Oyler, JM; Schoendorfer, D; Wstadik, AT, 1999
)
0.82
"A high performance liquid chromatography procedure has been developed for the simultaneous determination of guaifenesin pseudoephedrine-dextromethorphan and guaifenesin-pseudoephedrine in commercially available capsule dosage forms and guaifenesin-codeine in a commercial cough syrup dosage form."( HPLC determination of guaifenesin with selected medications on underivatized silica with an aqueous-organic mobile phase.
Stewart, JT; Wilcox, ML, 2000
)
0.49
" A significant dose-response relationship was observed for hair specimens."( The disposition of cocaine and opiate analytes in hair and fingernails of humans following cocaine and codeine administration.
Cone, EJ; Goldberger, BA; Joseph, RE; Ropero-Miller, JD, 2000
)
0.52
" In a second case study, a postoperative patient self-administered 960 mg/day (240 mg four times per day) of physician-prescribed oral codeine phosphate, and urine specimens were collected on the third day of the dosing regimen."( Identification of hydrocodone in human urine following controlled codeine administration.
Cone, EJ; Huestis, MA; Joseph, RE; Oyler, JM, 2000
)
0.75
" The result was supported a rational dose-response relationship for different doses of paracetamol and codeine in 17 additional trials with 1,195 patients."( Using evidence from different sources: an example using paracetamol 1000 mg plus codeine 60 mg.
Gavaghan, D; McQuay, HJ; Moore, RA; Smith, LA, 2001
)
0.75
" The article shows the usual dosage and "therapeutic", toxic and fatal concentrations."( [Pharmacokinetic and toxicokinetic parameters of some drugs of abuse].
Panas, M, 2001
)
0.31
" The need for clear guidelines regarding the drug's appropriate parenteral dosing and administration is essential."( Seizures with intravenous codeine phosphate.
Al Mohaimeed, SA; Zolezzi, M, 2001
)
0.61
" This article will address the safety and efficacy of acetaminophen, aspirin, and ibuprofen independently and in combination with currently available prescription dosage forms with a focus on pharmacology, pharmacotherapeutics, pharmacodynamics, and pharmacokinetics, including drug interactions at the CYP450 system."( Acetaminophen, aspirin, or Ibuprofen in combination analgesic products.
Barkin, RL,
)
0.13
" Awareness and application of this knowledge will improve drug use in clinical practice and provide the physician with further appreciation that standard drug dosing may not be appropriate in all patients."( Pharmacogenetics affects dosing, efficacy, and toxicity of cytochrome P450-metabolized drugs.
Bertino, JS; Nafziger, AN; Rogers, JF, 2002
)
0.31
" Concurrent dosing of dihydrocodeine and ebastine produced a significant place preference."( Effects of second generation of histamine H1 antagonists, cetirizine and ebastine, on the antitussive and rewarding effects of dihydrocodeine in mice.
Kamei, J; Miyata, S; Morita, K; Onodera, K, 2003
)
0.81
" These products may be abused and it has been reported that in order to avoid nonopioid toxicity, some users may attempt to separate the components of combination analgesics, by mixing the dosage form in water and passing it through a coffee filtration apparatus (coffee filters)."( The separation of codeine from nonprescription combination analgesic products.
Fleming, GF; Hughes, CM; McElnay, JC, 2003
)
0.65
" Demerol in small dosage is safe and effective."( An evaluation of obstetrical analgesia.
FIST, HS, 1954
)
0.23
"The results confirm the safety, efficacy and patient acceptability of the initial conversion and maintenance dosing recommendations for CR codeine from a combination opioid/nonopioid analgesic."( Evaluation of dosing guidelines for use of controlled-release codeine in chronic noncancer pain.
Arkinstall, W; Clark, AJ; Darke, A; Eisenhoffer, J; Harsanyi, Z; Hays, H; Moulin, D; Quigley, P; Russell, A; Watson, CP, 2003
)
0.76
" Each subject was administered oral codeine phosphate syrup in a dosage of 30 mg three times a day for five days."( The effect of hair color on the incorporation of codeine into human hair.
Augsburger, MP; Borges, CR; Krueger, GG; Mizuno, A; O'Neal, C; Rollins, DE; Slawson, MH; Wilkins, DG,
)
0.66
" ATC) dosing of acetaminophen with codeine, with or without nurse coaching, compared to standard care with as needed (i."( A randomized clinical trial of the effectiveness of a scheduled oral analgesic dosing regimen for the management of postoperative pain in children following tonsillectomy.
Holdridge-Zeuner, D; Lanier, B; Miaskowski, C; Paul, SM; Savedra, MC; Sutters, KA; Waite, S, 2004
)
0.6
"We report a case of probable poisoning with codeine phosphate in a 3-month-old infant, which was associated with excessive dosing and concomitant use of antihistamines."( A case of probable codeine poisoning in a young infant after the use of a proprietary cough and cold medicine.
Chan, R; Lee, AC; So, KT, 2004
)
0.91
" Mean total pain relief and the sum of pain intensity difference were also similar in the early period after dosing (0-4 hours)."( Onset of analgesia and analgesic efficacy of tramadol/acetaminophen and codeine/acetaminophen/ibuprofen in acute postoperative pain: a single-center, single-dose, randomized, active-controlled, parallel-group study in a dental surgery pain model.
Cha, IH; Jung, YS; Kim, DK; Kim, HJ; Kim, MK; Lee, EW, 2004
)
0.56
"A 73-year-old Taiwanese woman with end-stage renal disease received oral codeine phosphate 30 mg 4 times daily for her back and rib pain without adjustment of her dosage regimen."( Probable codeine phosphate-induced seizures.
Kao, SM; Kuo, SC; Lin, YC; Yang, YH, 2004
)
0.97
" It is imperative to adjust the codeine dosage regimen based on patients' renal function to avoid the potential toxicity with overdose."( Probable codeine phosphate-induced seizures.
Kao, SM; Kuo, SC; Lin, YC; Yang, YH, 2004
)
1.02
"Six focus group sessions with 27 former high and low dosage drug users, mainly of benzodiazepines, were conducted."( [Withdrawal of addictive drugs--patients' experiences?].
Steine, S; Torper, J, 2004
)
0.32
" Both high and low dosage users reported a significant increase in self esteem and ability to cope that was directly related to drug withdrawal and they reported a substantially improved quality of life."( [Withdrawal of addictive drugs--patients' experiences?].
Steine, S; Torper, J, 2004
)
0.32
" Its transnasal dosage form, which may be self-administered when the use of an opioid analgesic is appropriate, was previously shown to provide rapid relief of migraine pain."( Comparison of butorphanol nasal spray and fiorinal with codeine in the treatment of migraine.
Davidson, WJ; Diamond, S; Gawel, MJ; Goldstein, J; Reich, L; Sussman, NM; Winner, P,
)
0.38
"As part of a randomized clinical trial that compared three different analgesic dosing regimens ( Sutters et al."( Time-contingent dosing of an opioid analgesic after tonsillectomy does not increase moderate-to-severe side effects in children.
Holdridge-Zeuner, D; Lanier, B; Miaskowski, C; Paul, SM; Savedra, MC; Sutters, KA; Waite, S, 2005
)
0.33
" Tramadol has not been compared with codeine, ibuprofen, or correctly dosed paracetamol (step-1 analgesic)."( Tramadol oral solution: new drug. Poorly evaluated and potentially dangerous in children.
, 2005
)
0.6
" In clinical practice, combinations are usually given at the above-mentioned dosage three to four times a day."( Comparative trial of tramadol/paracetamol and codeine/paracetamol combination tablets on the vigilance of healthy volunteers.
Dubray, C; Estrade, M; Pickering, G, 2005
)
0.59
" Pharmacogenomics has led to several genetic tests that provide clinical dosing recommendations."( Pharmacogenomics and its implications for autoimmune disease.
Carleton, B; Hayden, MR; Katzov, H; Ross, CJ,
)
0.13
" In both groups, if pain intensity was rated as > 3 on the VAS at week 1 or 2, the dosage was doubled."( Codeine/acetaminophen and hydrocodone/acetaminophen combination tablets for the management of chronic cancer pain in adults: a 23-day, prospective, double-blind, randomized, parallel-group study.
Angel, AM; Castillo, JM; Del Pilar Castillo, M; Nuñez, PD; Ortiz, Y; Restrepo, JM; Rodriguez, JM; Rodriguez, MF; Rodriguez, RF, 2007
)
1.78
" Of the patients who received C/A, 58% responded to the initial dosage of 150/2500 mg/d, and 8% of the patients responded to the double dosage; 34% did not experience pain relief."( Codeine/acetaminophen and hydrocodone/acetaminophen combination tablets for the management of chronic cancer pain in adults: a 23-day, prospective, double-blind, randomized, parallel-group study.
Angel, AM; Castillo, JM; Del Pilar Castillo, M; Nuñez, PD; Ortiz, Y; Restrepo, JM; Rodriguez, JM; Rodriguez, MF; Rodriguez, RF, 2007
)
1.78
" The interaction between these two agents was characterized by isobolographic analysis using a fixed-ratio dosing strategy."( Additive, but not synergistic antinociceptive effect of codeine and indomethacin combinations in the formalin test in the rat.
Arredondo-Garza, T; Castañeda-Hernández, G; Jiménez-Andrade, M; Lozano-Cuenca, J, 2007
)
0.59
" There may be a dose-response relationship between maternal codeine use and neonatal toxicity, and strong concordance between maternal-infant CNS depressive symptoms."( Pharmacogenetics of neonatal opioid toxicity following maternal use of codeine during breastfeeding: a case-control study.
Carleton, BC; Gaedigk, A; Hayden, MR; Koren, G; Leeder, JS; Madadi, P; Ross, CJ, 2009
)
0.83
"Because of the variability of drop size drug dosage, dosage "by drops" is unprecise and may result in accidental overdose."( Drug dosing error with drops: severe clinical course of codeine intoxication in twins.
Auwärter, V; Ferreirós, N; Hentschel, R; Hermanns-Clausen, M; Müller, C; Pahl, A; Superti-Furga, A; Trittler, R; Weinmann, W, 2009
)
0.6
" Initial dose of codeine is 60 mg x day(-1) and the dosage should be increased or decreased according to pain intensity, patients' general condition and age."( [Indication and usage of opioids except morphine for chronic non-malignant intractable pain].
Saeki, S, 2008
)
0.69
" Therapeutic considerations in counseling breastfeeding mothers include susceptibility to drug toxicity of the very young and/or premature infant, significant interindividual variations in drug response, the dose-response relationship with respect to drug toxicity, and the role of pharmacogenetics in both the mother and the infant."( Safety issues of maternal drug therapy during breastfeeding.
Berlin, CM; Paul, IM; Vesell, ES, 2009
)
0.35
" We then administered codeine, which alleviated the pain; an increase in the dosage led to complete pain remission."( [Opioid effectiveness for neuropathic pain in a patient with glossopharyngeal neuralgia].
Hirano, T; Kouzaki, Y; Otsuka, T; Takita, T; Tawara, S; Uchino, M, 2009
)
0.67
" Given the added effect of low neonatal elimination capacity for morphine, potentially toxic morphine plasma concentrations can be reached within 4 days in the neonate after repeated codeine dosing to the mother."( Risk to the breast-fed neonate from codeine treatment to the mother: a quantitative mechanistic modeling study.
Ahr, G; Coboeken, K; Edginton, AN; Lippert, J; Willmann, S, 2009
)
0.82
" In this article pharmacokinetics, pharmacodynamics, dosing guidelines, adverse effects and clinical studies of DHC in pain management are shown with focus on cancer pain."( Dihydrocodeine as an opioid analgesic for the treatment of moderate to severe chronic pain.
Leppert, W, 2010
)
0.82
" Several pharmacogenomics tests are currently in clinical use to provide dosing recommendations, and the number of pharmacogenomics tests is expected to significantly increase in the future."( The Canadian Pharmacogenomics Network for Drug Safety: a model for safety pharmacology.
Brunham, LR; Carleton, BC; Hayden, MR; Koren, G; Loo, TT; Pussegoda, K; Rieder, MJ; Ross, CJ; Sistonen, J; Visscher, H, 2010
)
0.36
"org) is to provide information relating to the interpretation of CYP2D6 genotype test results to guide the dosing of codeine."( Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype.
Callaghan, JT; Crews, KR; Dunnenberger, HM; Gaedigk, A; Kharasch, ED; Klein, TE; Shen, DD; Skaar, TC, 2012
)
0.82
" Methadone treatment was switched to SROM with flexible dosing and vice versa according to period and sequence of treatment."( Maintenance treatment for opioid dependence with slow-release oral morphine: a randomized cross-over, non-inferiority study versus methadone.
Backmund, M; Beck, T; Haasen, C; Reimer, J; Ruckes, C; Schuler, C; Verthein, U; Walcher, S, 2014
)
0.4
"The present monograph reviews data relevant to applying the biowaiver procedure for the approval of immediate-release multisource solid dosage forms containing codeine phosphate."( Biowaiver monographs for immediate-release solid oral dosage forms: codeine phosphate.
Abrahamsson, B; Amidon, GL; Cristofoletti, R; Dahan, A; Dressman, JB; Groot, DW; Kopp, S; Langguth, P; Polli, JE; Shah, VP; Wolk, O; Zur, M, 2014
)
0.83
" Discussion and dissemination of indigenous harm reduction tactics included the learning to appreciate codeine's effect via moderated use in optimal settings, avoidance of tolerance by use of informed dosing schedules, cold water extraction of codeine, and using codeine as an alternative to stronger opioids."( Nod and wave: an Internet study of the codeine intoxication phenomenon.
Van Hout, MC, 2015
)
0.9
" We accepted any formulation, dosage regimen, and route of administration of codeine, and both placebo and active controls."( Codeine, alone and with paracetamol (acetaminophen), for cancer pain.
Bell, RF; Derry, S; Jackson, KC; Strassels, S; Straube, C; Straube, S; Wiffen, PJ, 2014
)
2.07
"A new HPLC method for separation and determination of impurities in paracetamol, codeine phosphate hemihydrate and pitophenone hydrochloride in the presence of fenpiverinium bromide in combined suppository dosage form was developed and validated."( Separation and determination of impurities in paracetamol, codeine and pitophenone in the presence of fenpiverinium in combined suppository dosage form.
Coufal, P; Hanzlík, P; Jedlička, A; Vojta, J, 2015
)
0.89
" Our study suggests that pharmacogenetics for personalized dosing might be most effectively advanced by studying the interplay between pharmacogenetics, population pharmacokinetics, and clinical pharmacokinetics."( CYP2D6 phenotype-specific codeine population pharmacokinetics.
Boston, RC; Daly Linares, AL; Fudin, J; Linares, OA; Schiesser, WE, 2015
)
0.72
" The results clearly indicate that the physico-chemical properties of the drug and the matrix systems are crucial for the design of ethanol-resistant dosage forms."( Alcohol dose dumping: The influence of ethanol on hot-melt extruded pellets comprising solid lipids.
Feichtinger, A; Jedinger, N; Khinast, J; Mohr, S; Roblegg, E; Schrank, S, 2015
)
0.42
" As the drug is commonly available appropriate titration and dosing and knowledge of its metabolism and possible adverse effects are important for safe prescription of DHC."( Dihydrocodeine: safety concerns.
Leppert, W; Woroń, J, 2016
)
0.89
" Because of a previously reported 82% error rate in handwritten discharge narcotic prescriptions, we developed a computerized, web-based, controlled substance prescription writer that includes weight-based dosing logic and alerts to reduce the error rate to (virtually) zero."( An Analysis of 34,218 Pediatric Outpatient Controlled Substance Prescriptions.
George, JA; Hunsberger, J; Lee, BH; Lehmann, CU; Park, PS; Shay, JE; White, ED; Yaster, M, 2016
)
0.43
" Metabolic response and dosage variability place children at increased risk of experiencing such side effects."( Codeine versus placebo for chronic cough in children.
Chang, AB; Gardiner, SJ; Marchant, JM; Petsky, HL, 2016
)
1.88
"Although routine preoperative genotyping to identify children at risk and personalized opioid use for pediatric perioperative pain management is still a distant reality, current known implications of CYP2D6 pharmacogenetics on codeine use shows that pharmacogenetics has the potential to guide anesthesia providers on perioperative opioid selection and dosing to maximize efficacy and safety."( Codeine and opioid metabolism: implications and alternatives for pediatric pain management.
Chidambaran, V; Mahmoud, M; Sadhasivam, S, 2017
)
2.08
"Medication use is common in pregnancy, yet for most medications the optimal formulation and dosage have not been described specifically for pregnant women."( Fundamentals of Clinical Pharmacology With Application for Pregnant Women.
Dotters-Katz, SK; Onslow, M; Patil, AS; Pierson, RC; Schmoll, MS; Sheng, J, 2017
)
0.46
"Understanding properties and mechanisms that govern drug degradation in the solid state is of high importance to ensure drug stability and safety of solid dosage forms."( Drug-Excipient Interactions in the Solid State: The Role of Different Stress Factors.
Brunsteiner, M; Davis, A; Gressl, C; Gruber-Woelfler, H; Khinast, JG; Landis, M; Paudel, A; Pencheva, K; Scrivens, G; Sluggett, GW; Wood, GPF, 2017
)
0.46
" Further research to assess adverse events and other dosing may be warranted."( Effect of a Single Dose of Oral Opioid and Nonopioid Analgesics on Acute Extremity Pain in the Emergency Department: A Randomized Clinical Trial.
Baer, J; Barnaby, DP; Bijur, PE; Chang, AK; Esses, D, 2017
)
0.46
" A patient-targeted approach using pharmacogenomics may mitigate adverse effects by individualizing the selection and dosing of these analgesics."( The Prevalence of Ultrarapid Metabolizers of Codeine in a Diverse Urban Population.
Bent, JP; Morrow, BE; Ow, TJ; Reynolds, D; Virbalas, J, 2019
)
0.77
" Results showed that all subjects who consumed low dosage of poppy seeds either in single meal or multiple meals experiment were found negative."( Profiling of morphine and codeine in urine after the ingestion of curry containing poppy seed as an evidence for opiates defence in Malaysia.
Gan, CY; Isahak, M; Mahad, NH; Mohd Akir, F; Mohd Fazil, NF; Muhamad Noh, H; Nasir, R; Rahmat, R; Samad, HA; Zainuddin, Z, 2019
)
0.81
" Integrating pharmacogenomics into clinical practice to assist in drug selection and dosing has the potential to improve the outcomes of treatment, reduce the risk of drug-induced morbidity and death, and be cost-effective."( Pharmacogenomics: An evolving clinical tool for precision medicine.
Eng, C; Erwin, AL; Hicks, JK; Hockings, JK; Mason, NT; Pasternak, AL, 2020
)
0.56
" Paracetamol has a very flat analgesic dose-response profile."( Analgesic effect of oral ibuprofen 400, 600, and 800 mg; paracetamol 500 and 1000 mg; and paracetamol 1000 mg plus 60 mg codeine in acute postoperative pain: a single-dose, randomized, placebo-controlled, and double-blind study.
Lyngstad, G; Skjelbred, P; Skoglund, LA; Swanson, DM, 2021
)
0.83
"Efficacy and rapid onset of postsurgical oral pain relief are critical to improve clinical outcomes and reduce the risk of excessive dosing with analgesic drugs."( COMPARATIVE ANALGESIC EFFECTS OF SINGLE-DOSE PREOPERATIVE ADMINISTRATION OF PARACETAMOL (ACETAMINOPHEN) 500 mg PLUS CODEINE 30 mg AND IBUPROFEN 400 mg ON PAIN AFTER THIRD MOLAR SURGERY.
Annibali, S; Cristalli, MP; La Monaca, G; Polimeni, A; Pompa, G; Pranno, N; Vozza, I, 2021
)
0.83
"5 billion dosage units (adjusted: 42."( Sales of Over-the-Counter Products Containing Codeine in 31 Countries, 2013-2019: A Retrospective Observational Study.
Aronson, JK; Goldacre, B; Heneghan, C; Hobbs, FDR; MacKenna, B; Richards, GC, 2022
)
0.98
" The method was successfully applied to the syrup dosage form."( Determination of pholcodine alone or in combination with ephedrine in human plasma using fluorescence spectroscopy.
Belal, F; Elmansi, H; Magdy, G, 2022
)
0.72
"The scoping review identified 57 studies with most data available on their tolerability (68% local, 54% systemic), clinical effects (82%), details on dosage (96%) and routes of application (100%)."( Subcutaneous Drugs and Off-label Use in Hospice and Palliative Care: A Scoping Review.
Dürr, F; Jean-Petit-Matile, S; Kobleder, A; Meyer-Massetti, C; Wernli, U, 2022
)
0.72
" OPRM1 and COMT are receiving increasing attention and have implications for all opioids, with changes in opioid dosage requirements observed but they have not yet been studied widely enough to be considered clinically actionable."( The Role of Pharmacogenomics in Opioid Prescribing.
Philip, J; Rubio, J; Somogyi, AA; Wong, AK, 2022
)
0.72
" ITS analyses showed that immediately postrescheduling, quarterly hydrocodone dispensing decreased by 177M dosage units while codeine, oxycodone, and morphine dispensing increased by 49M, 62M, and 4M dosage units, respectively."( The impact of hydrocodone rescheduling on utilization, abuse, misuse, and overdose deaths.
Ajao, A; Chai, GP; Ding, Y; Gill, R; Karami, S; Major, JM; McAninch, J; Meyer, T; Secora, A; Wong, J; Zhang, D; Zhao, Y, 2023
)
1.12
" Healthcare providers should use their clinical judgment and reference different established dosing guidelines to determine the appropriate dose of codeine for individual patients."( A software tool to adjust codeine dose based on CYP2D6 gene-pair polymorphisms and drug-drug interactions.
Nakad, Z; Saab, Y, 2023
)
1.41
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (7)

RoleDescription
opioid analgesicA narcotic or opioid substance, synthetic or semisynthetic agent producing profound analgesia, drowsiness, and changes in mood.
antitussiveAn agent that suppresses cough. Antitussives have a central or a peripheral action on the cough reflex, or a combination of both. Compare with expectorants, which are considered to increase the volume of secretions in the respiratory tract, so facilitating their removal by ciliary action and coughing, and mucolytics, which decrease the viscosity of mucus, facilitating its removal by ciliary action and expectoration.
opioid receptor agonistAn agent that selectively binds to and activates an opioid receptor.
prodrugA compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.
xenobioticA xenobiotic (Greek, xenos "foreign"; bios "life") is a compound that is foreign to a living organism. Principal xenobiotics include: drugs, carcinogens and various compounds that have been introduced into the environment by artificial means.
environmental contaminantAny minor or unwanted substance introduced into the environment that can have undesired effects.
drug allergenAny drug which causes the onset of an allergic reaction.
[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 (2)

ClassDescription
organic heteropentacyclic compound
morphinane alkaloidAn isoquinoline alkaloid based on a morphinan skeleton and its substituted derivatives.
[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 (3)

PathwayProteinsCompounds
Codeine Action Pathway3420
Codeine Metabolism Pathway411
Codeine and morphine metabolism07

Protein Targets (19)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
GLI family zinc finger 3Homo sapiens (human)Potency17.31660.000714.592883.7951AID1259369; AID1259392
AR proteinHomo sapiens (human)Potency61.44150.000221.22318,912.5098AID743040
retinoic acid nuclear receptor alpha variant 1Homo sapiens (human)Potency36.63250.003041.611522,387.1992AID1159552; AID1159555
nuclear factor erythroid 2-related factor 2 isoform 1Homo sapiens (human)Potency29.65610.000627.21521,122.0200AID743202; AID743219
[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)
Solute carrier family 22 member 1 Homo sapiens (human)IC50 (µMol)235.50000.21005.553710.0000AID1526751
Cytochrome P450 2D26Rattus norvegicus (Norway rat)IC50 (µMol)238.00000.09402.16285.6000AID54564
Cytochrome P450 2D6Homo sapiens (human)IC50 (µMol)171.00000.00002.015110.0000AID54564; AID54570
Delta-type opioid receptorMus musculus (house mouse)IC50 (µMol)10.00000.00010.729810.0000AID150244
Kappa-type opioid receptorMus musculus (house mouse)IC50 (µMol)10.00000.00131.538010.0000AID150244
Mu-type opioid receptorHomo sapiens (human)IC50 (µMol)0.10500.00010.813310.0000AID150822
Mu-type opioid receptorHomo sapiens (human)Ki3.51350.00000.419710.0000AID327878; AID330420
Delta-type opioid receptorHomo sapiens (human)IC50 (µMol)9.30000.00020.75218.0140AID148090
Delta-type opioid receptorHomo sapiens (human)Ki52.20700.00000.59789.9300AID330421
Kappa-type opioid receptorHomo sapiens (human)IC50 (µMol)15.00000.00001.201110.0000AID147865
Kappa-type opioid receptorHomo sapiens (human)Ki25.41100.00000.362410.0000AID330422
Mu-type opioid receptorMus musculus (house mouse)IC50 (µMol)10.00000.00081.699210.0000AID150244
Potassium voltage-gated channel subfamily H member 2Homo sapiens (human)IC50 (µMol)301.99500.00091.901410.0000AID243151
Cytochrome P450 2D4Rattus norvegicus (Norway rat)IC50 (µMol)2,216.00001.70001.70001.7000AID54566
[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)
Mu-type opioid receptorHomo sapiens (human)EC50 (µMol)6.10000.00000.32639.4000AID327877
Mas-related G-protein coupled receptor member X2Homo sapiens (human)EC50 (µMol)8.40000.14003.73818.9000AID1802708; AID1802709
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Other Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (124)

Processvia Protein(s)Taxonomy
xenobiotic metabolic processSolute carrier family 22 member 1 Homo sapiens (human)
neurotransmitter transportSolute carrier family 22 member 1 Homo sapiens (human)
serotonin transportSolute carrier family 22 member 1 Homo sapiens (human)
establishment or maintenance of transmembrane electrochemical gradientSolute carrier family 22 member 1 Homo sapiens (human)
organic cation transportSolute carrier family 22 member 1 Homo sapiens (human)
quaternary ammonium group transportSolute carrier family 22 member 1 Homo sapiens (human)
prostaglandin transportSolute carrier family 22 member 1 Homo sapiens (human)
monoamine transportSolute carrier family 22 member 1 Homo sapiens (human)
putrescine transportSolute carrier family 22 member 1 Homo sapiens (human)
spermidine transportSolute carrier family 22 member 1 Homo sapiens (human)
acetylcholine transportSolute carrier family 22 member 1 Homo sapiens (human)
dopamine transportSolute carrier family 22 member 1 Homo sapiens (human)
norepinephrine transportSolute carrier family 22 member 1 Homo sapiens (human)
thiamine transportSolute carrier family 22 member 1 Homo sapiens (human)
xenobiotic transportSolute carrier family 22 member 1 Homo sapiens (human)
epinephrine transportSolute carrier family 22 member 1 Homo sapiens (human)
serotonin uptakeSolute carrier family 22 member 1 Homo sapiens (human)
norepinephrine uptakeSolute carrier family 22 member 1 Homo sapiens (human)
thiamine transmembrane transportSolute carrier family 22 member 1 Homo sapiens (human)
metanephric proximal tubule developmentSolute carrier family 22 member 1 Homo sapiens (human)
purine-containing compound transmembrane transportSolute carrier family 22 member 1 Homo sapiens (human)
dopamine uptakeSolute carrier family 22 member 1 Homo sapiens (human)
monoatomic cation transmembrane transportSolute carrier family 22 member 1 Homo sapiens (human)
transport across blood-brain barrierSolute carrier family 22 member 1 Homo sapiens (human)
(R)-carnitine transmembrane transportSolute carrier family 22 member 1 Homo sapiens (human)
acyl carnitine transmembrane transportSolute carrier family 22 member 1 Homo sapiens (human)
spermidine transmembrane transportSolute carrier family 22 member 1 Homo sapiens (human)
cellular detoxificationSolute carrier family 22 member 1 Homo sapiens (human)
xenobiotic transport across blood-brain barrierSolute carrier family 22 member 1 Homo sapiens (human)
xenobiotic metabolic processCytochrome P450 2D6Homo sapiens (human)
steroid metabolic processCytochrome P450 2D6Homo sapiens (human)
cholesterol metabolic processCytochrome P450 2D6Homo sapiens (human)
estrogen metabolic processCytochrome P450 2D6Homo sapiens (human)
coumarin metabolic processCytochrome P450 2D6Homo sapiens (human)
alkaloid metabolic processCytochrome P450 2D6Homo sapiens (human)
alkaloid catabolic processCytochrome P450 2D6Homo sapiens (human)
monoterpenoid metabolic processCytochrome P450 2D6Homo sapiens (human)
isoquinoline alkaloid metabolic processCytochrome P450 2D6Homo sapiens (human)
xenobiotic catabolic processCytochrome P450 2D6Homo sapiens (human)
retinol metabolic processCytochrome P450 2D6Homo sapiens (human)
long-chain fatty acid biosynthetic processCytochrome P450 2D6Homo sapiens (human)
negative regulation of bindingCytochrome P450 2D6Homo sapiens (human)
oxidative demethylationCytochrome P450 2D6Homo sapiens (human)
negative regulation of cellular organofluorine metabolic processCytochrome P450 2D6Homo sapiens (human)
arachidonic acid metabolic processCytochrome P450 2D6Homo 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)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messengerMu-type opioid receptorHomo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathwayMu-type opioid receptorHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayMu-type opioid receptorHomo sapiens (human)
sensory perceptionMu-type opioid receptorHomo sapiens (human)
negative regulation of cell population proliferationMu-type opioid receptorHomo sapiens (human)
sensory perception of painMu-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor signaling pathwayMu-type opioid receptorHomo sapiens (human)
behavioral response to ethanolMu-type opioid receptorHomo sapiens (human)
positive regulation of neurogenesisMu-type opioid receptorHomo sapiens (human)
negative regulation of Wnt protein secretionMu-type opioid receptorHomo sapiens (human)
positive regulation of ERK1 and ERK2 cascadeMu-type opioid receptorHomo sapiens (human)
calcium ion transmembrane transportMu-type opioid receptorHomo sapiens (human)
cellular response to morphineMu-type opioid receptorHomo sapiens (human)
regulation of cellular response to stressMu-type opioid receptorHomo sapiens (human)
regulation of NMDA receptor activityMu-type opioid receptorHomo sapiens (human)
neuropeptide signaling pathwayMu-type opioid receptorHomo sapiens (human)
immune responseDelta-type opioid receptorHomo sapiens (human)
G protein-coupled receptor signaling pathwayDelta-type opioid receptorHomo sapiens (human)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messengerDelta-type opioid receptorHomo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathwayDelta-type opioid receptorHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayDelta-type opioid receptorHomo sapiens (human)
adult locomotory behaviorDelta-type opioid receptorHomo sapiens (human)
negative regulation of gene expressionDelta-type opioid receptorHomo sapiens (human)
negative regulation of protein-containing complex assemblyDelta-type opioid receptorHomo sapiens (human)
positive regulation of CREB transcription factor activityDelta-type opioid receptorHomo sapiens (human)
positive regulation of peptidyl-serine phosphorylationDelta-type opioid receptorHomo sapiens (human)
response to nicotineDelta-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor signaling pathwayDelta-type opioid receptorHomo sapiens (human)
eating behaviorDelta-type opioid receptorHomo sapiens (human)
regulation of mitochondrial membrane potentialDelta-type opioid receptorHomo sapiens (human)
regulation of calcium ion transportDelta-type opioid receptorHomo sapiens (human)
cellular response to growth factor stimulusDelta-type opioid receptorHomo sapiens (human)
cellular response to hypoxiaDelta-type opioid receptorHomo sapiens (human)
cellular response to toxic substanceDelta-type opioid receptorHomo sapiens (human)
neuropeptide signaling pathwayDelta-type opioid receptorHomo sapiens (human)
immune responseKappa-type opioid receptorHomo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathwayKappa-type opioid receptorHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayKappa-type opioid receptorHomo sapiens (human)
chemical synaptic transmissionKappa-type opioid receptorHomo sapiens (human)
sensory perceptionKappa-type opioid receptorHomo sapiens (human)
locomotory behaviorKappa-type opioid receptorHomo sapiens (human)
sensory perception of painKappa-type opioid receptorHomo sapiens (human)
adenylate cyclase-inhibiting opioid receptor signaling pathwayKappa-type opioid receptorHomo sapiens (human)
response to insulinKappa-type opioid receptorHomo sapiens (human)
positive regulation of dopamine secretionKappa-type opioid receptorHomo sapiens (human)
negative regulation of luteinizing hormone secretionKappa-type opioid receptorHomo sapiens (human)
response to nicotineKappa-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor signaling pathwayKappa-type opioid receptorHomo sapiens (human)
maternal behaviorKappa-type opioid receptorHomo sapiens (human)
eating behaviorKappa-type opioid receptorHomo sapiens (human)
response to estrogenKappa-type opioid receptorHomo sapiens (human)
estrous cycleKappa-type opioid receptorHomo sapiens (human)
response to ethanolKappa-type opioid receptorHomo sapiens (human)
regulation of saliva secretionKappa-type opioid receptorHomo sapiens (human)
behavioral response to cocaineKappa-type opioid receptorHomo sapiens (human)
sensory perception of temperature stimulusKappa-type opioid receptorHomo sapiens (human)
defense response to virusKappa-type opioid receptorHomo sapiens (human)
cellular response to lipopolysaccharideKappa-type opioid receptorHomo sapiens (human)
cellular response to glucose stimulusKappa-type opioid receptorHomo sapiens (human)
positive regulation of p38MAPK cascadeKappa-type opioid receptorHomo sapiens (human)
positive regulation of potassium ion transmembrane transportKappa-type opioid receptorHomo sapiens (human)
response to acrylamideKappa-type opioid receptorHomo sapiens (human)
positive regulation of eating behaviorKappa-type opioid receptorHomo sapiens (human)
conditioned place preferenceKappa-type opioid receptorHomo sapiens (human)
neuropeptide signaling pathwayKappa-type opioid receptorHomo sapiens (human)
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of heart rate by hormonePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of membrane potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
positive regulation of DNA-templated transcriptionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion homeostasisPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cardiac muscle contractionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of ventricular cardiac muscle cell membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cellular response to xenobiotic stimulusPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane depolarization during action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion export across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
negative regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
positive regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
negative regulation of potassium ion export across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion import across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
sensory perception of painMas-related G-protein coupled receptor member X2Homo sapiens (human)
sleepMas-related G-protein coupled receptor member X2Homo sapiens (human)
positive regulation of cytokinesisMas-related G-protein coupled receptor member X2Homo sapiens (human)
mast cell degranulationMas-related G-protein coupled receptor member X2Homo sapiens (human)
mast cell activationMas-related G-protein coupled receptor member X2Homo sapiens (human)
G protein-coupled receptor signaling pathwayMas-related G-protein coupled receptor member X2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (51)

Processvia Protein(s)Taxonomy
acetylcholine transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
neurotransmitter transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
dopamine:sodium symporter activitySolute carrier family 22 member 1 Homo sapiens (human)
norepinephrine:sodium symporter activitySolute carrier family 22 member 1 Homo sapiens (human)
protein bindingSolute carrier family 22 member 1 Homo sapiens (human)
monoamine transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
secondary active organic cation transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
organic anion transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
organic cation transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
prostaglandin transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
pyrimidine nucleoside transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
thiamine transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
putrescine transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
spermidine transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
quaternary ammonium group transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
toxin transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
identical protein bindingSolute carrier family 22 member 1 Homo sapiens (human)
xenobiotic transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
(R)-carnitine transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
monooxygenase activityCytochrome P450 2D6Homo sapiens (human)
iron ion bindingCytochrome P450 2D6Homo sapiens (human)
oxidoreductase activityCytochrome P450 2D6Homo 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 2D6Homo sapiens (human)
heme bindingCytochrome P450 2D6Homo sapiens (human)
anandamide 8,9 epoxidase activityCytochrome P450 2D6Homo sapiens (human)
anandamide 11,12 epoxidase activityCytochrome P450 2D6Homo sapiens (human)
anandamide 14,15 epoxidase activityCytochrome P450 2D6Homo sapiens (human)
retinoic acid bindingUDP-glucuronosyltransferase 2B7Homo sapiens (human)
glucuronosyltransferase activityUDP-glucuronosyltransferase 2B7Homo sapiens (human)
G-protein alpha-subunit bindingMu-type opioid receptorHomo sapiens (human)
G protein-coupled receptor activityMu-type opioid receptorHomo sapiens (human)
beta-endorphin receptor activityMu-type opioid receptorHomo sapiens (human)
voltage-gated calcium channel activityMu-type opioid receptorHomo sapiens (human)
protein bindingMu-type opioid receptorHomo sapiens (human)
morphine receptor activityMu-type opioid receptorHomo sapiens (human)
G-protein beta-subunit bindingMu-type opioid receptorHomo sapiens (human)
neuropeptide bindingMu-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor activityDelta-type opioid receptorHomo sapiens (human)
protein bindingDelta-type opioid receptorHomo sapiens (human)
receptor serine/threonine kinase bindingDelta-type opioid receptorHomo sapiens (human)
G protein-coupled enkephalin receptor activityDelta-type opioid receptorHomo sapiens (human)
neuropeptide bindingDelta-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor activityKappa-type opioid receptorHomo sapiens (human)
protein bindingKappa-type opioid receptorHomo sapiens (human)
receptor serine/threonine kinase bindingKappa-type opioid receptorHomo sapiens (human)
dynorphin receptor activityKappa-type opioid receptorHomo sapiens (human)
neuropeptide bindingKappa-type opioid receptorHomo sapiens (human)
transcription cis-regulatory region bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
inward rectifier potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
delayed rectifier potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
ubiquitin protein ligase bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
identical protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
protein homodimerization activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
C3HC4-type RING finger domain bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
scaffold protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
G protein-coupled receptor activityMas-related G-protein coupled receptor member X2Homo sapiens (human)
neuropeptide bindingMas-related G-protein coupled receptor member X2Homo sapiens (human)
mast cell secretagogue receptor activityMas-related G-protein coupled receptor member X2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (35)

Processvia Protein(s)Taxonomy
plasma membraneSolute carrier family 22 member 1 Homo sapiens (human)
basal plasma membraneSolute carrier family 22 member 1 Homo sapiens (human)
membraneSolute carrier family 22 member 1 Homo sapiens (human)
basolateral plasma membraneSolute carrier family 22 member 1 Homo sapiens (human)
apical plasma membraneSolute carrier family 22 member 1 Homo sapiens (human)
lateral plasma membraneSolute carrier family 22 member 1 Homo sapiens (human)
presynapseSolute carrier family 22 member 1 Homo sapiens (human)
mitochondrionCytochrome P450 2D6Homo sapiens (human)
endoplasmic reticulumCytochrome P450 2D6Homo sapiens (human)
endoplasmic reticulum membraneCytochrome P450 2D6Homo sapiens (human)
cytoplasmCytochrome P450 2D6Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 2D6Homo sapiens (human)
endoplasmic reticulum membraneUDP-glucuronosyltransferase 2B7Homo sapiens (human)
membraneUDP-glucuronosyltransferase 2B7Homo sapiens (human)
plasma membraneKappa-type opioid receptorMus musculus (house mouse)
endosomeMu-type opioid receptorHomo sapiens (human)
endoplasmic reticulumMu-type opioid receptorHomo sapiens (human)
Golgi apparatusMu-type opioid receptorHomo sapiens (human)
plasma membraneMu-type opioid receptorHomo sapiens (human)
axonMu-type opioid receptorHomo sapiens (human)
dendriteMu-type opioid receptorHomo sapiens (human)
perikaryonMu-type opioid receptorHomo sapiens (human)
synapseMu-type opioid receptorHomo sapiens (human)
plasma membraneMu-type opioid receptorHomo sapiens (human)
neuron projectionMu-type opioid receptorHomo sapiens (human)
plasma membraneDelta-type opioid receptorHomo sapiens (human)
synaptic vesicle membraneDelta-type opioid receptorHomo sapiens (human)
dendrite membraneDelta-type opioid receptorHomo sapiens (human)
presynaptic membraneDelta-type opioid receptorHomo sapiens (human)
axon terminusDelta-type opioid receptorHomo sapiens (human)
spine apparatusDelta-type opioid receptorHomo sapiens (human)
postsynaptic density membraneDelta-type opioid receptorHomo sapiens (human)
neuronal dense core vesicleDelta-type opioid receptorHomo sapiens (human)
plasma membraneDelta-type opioid receptorHomo sapiens (human)
neuron projectionDelta-type opioid receptorHomo sapiens (human)
nucleoplasmKappa-type opioid receptorHomo sapiens (human)
mitochondrionKappa-type opioid receptorHomo sapiens (human)
cytosolKappa-type opioid receptorHomo sapiens (human)
plasma membraneKappa-type opioid receptorHomo sapiens (human)
membraneKappa-type opioid receptorHomo sapiens (human)
sarcoplasmic reticulumKappa-type opioid receptorHomo sapiens (human)
T-tubuleKappa-type opioid receptorHomo sapiens (human)
dendriteKappa-type opioid receptorHomo sapiens (human)
synaptic vesicle membraneKappa-type opioid receptorHomo sapiens (human)
presynaptic membraneKappa-type opioid receptorHomo sapiens (human)
perikaryonKappa-type opioid receptorHomo sapiens (human)
axon terminusKappa-type opioid receptorHomo sapiens (human)
postsynaptic membraneKappa-type opioid receptorHomo sapiens (human)
plasma membraneKappa-type opioid receptorHomo sapiens (human)
neuron projectionKappa-type opioid receptorHomo sapiens (human)
plasma membraneMu-type opioid receptorMus musculus (house mouse)
plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cell surfacePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
perinuclear region of cytoplasmPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel complexPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
inward rectifier potassium channel complexPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membraneMas-related G-protein coupled receptor member X2Homo sapiens (human)
plasma membraneMas-related G-protein coupled receptor member X2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (196)

Assay IDTitleYearJournalArticle
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.
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.
AID1057825Activity at UDP-glucuronosyltransferase in Sprague-Dawley rat liver microsomes assessed as morphine conversion to M3G at 1 uM by Michaelis-Menten plot analysis2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID1209593Dissociation constant, pKa of the acidic compound by capillary electrophoresis-mass spectrometry analysis2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Measurement of unbound drug exposure in brain: modeling of pH partitioning explains diverging results between the brain slice and brain homogenate methods.
AID125688Antagonistic potency of the compound; not active1992Journal of medicinal chemistry, Oct-02, Volume: 35, Issue:20
Alfred Burger Award address. A half century in medicinal chemistry with major emphasis on pain-relieving drugs and their antagonists.
AID1526731Substrate activity at human OCT1 expressed in HEK293 cells assessed as increase in compound uptake at 0.05 uM incubated for 2 mins by LC-MS/MS analysis relative to control empty vector transfected cells2019Journal of medicinal chemistry, 11-14, Volume: 62, Issue:21
Opioids as Substrates and Inhibitors of the Genetically Highly Variable Organic Cation Transporter OCT1.
AID330422Displacement of [3H]diprenorphine from recombinant kappa opioid receptor expressed in CHO cells2008Journal of medicinal chemistry, Apr-10, Volume: 51, Issue:7
Opioids and efflux transporters. Part 2: P-glycoprotein substrate activity of 3- and 6-substituted morphine analogs.
AID425653Renal clearance in human2009Journal of medicinal chemistry, Aug-13, Volume: 52, Issue:15
Physicochemical determinants of human renal clearance.
AID1057812Competitive inhibition of UDP-glucuronosyltransferase in Sprague-Dawley rat liver microsomes assessed as morphine conversion to M3G up to 5 uM by Lineweaver-Burk plot analysis2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID330421Displacement of [3H]diprenorphine from recombinant delta opioid receptor expressed in C6 cells2008Journal of medicinal chemistry, Apr-10, Volume: 51, Issue:7
Opioids and efflux transporters. Part 2: P-glycoprotein substrate activity of 3- and 6-substituted morphine analogs.
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.
AID425652Total body clearance in human2009Journal of medicinal chemistry, Aug-13, Volume: 52, Issue:15
Physicochemical determinants of human renal clearance.
AID327875Activation of human mu opioid receptor expressed in HEK293a cells co-expressing YFP-labelled alphai1 and CFP-labelled beta1gamma2 Gi subunits assessed as decrease in fluorescence resonance energy transfer signal at 100 uM relative to morphine2007The Journal of biological chemistry, Sep-14, Volume: 282, Issue:37
Live cell monitoring of mu-opioid receptor-mediated G-protein activation reveals strong biological activity of close morphine biosynthetic precursors.
AID604024Unbound brain to plasma concentration ratio in Sprague-Dawley rat administered in casettes of 2/3 drugs at 4 hr constant rate intravenous infusions using flow rate of 1 (ml/kg)/hr corresponding to dosage rate of 2 (umol/kg)/hr2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
Structure-brain exposure relationships in rat and human using a novel data set of unbound drug concentrations in brain interstitial and cerebrospinal fluids.
AID320419Displacement of 3.0 nM [3H]etorphine from opioid receptor in rat cerebrum2008Bioorganic & medicinal chemistry, Jan-15, Volume: 16, Issue:2
The influence of esters and carboxylic acids as the N-substituent of opioids. Part 1: Benzomorphans.
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.
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.
AID624621Specific activity of expressed human recombinant UGT2B7Y2000Annual review of pharmacology and toxicology, , Volume: 40Human UDP-glucuronosyltransferases: metabolism, expression, and disease.
AID127831Narcotic agonist activity using acetic acid induced writhing in the mouse upon subcutaneous administration1983Journal of medicinal chemistry, Jul, Volume: 26, Issue:7
Analgesic narcotic antagonists. 15. Potent narcotic agonist 7 beta-(arylalkyl)-4,5 alpha-epoxymorphinans.
AID151584Binding constant for the agonist state was measured for its ability to displace [3H]naloxone from opioid mu 1 receptor buffered homogenate of rat brain membranes1988Journal of medicinal chemistry, Mar, Volume: 31, Issue:3
Structure-activity relationships for drugs binding to the agonist and antagonist states of the primary morphine receptor.
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.
AID19424Partition coefficient (logD7.4)2001Journal of medicinal chemistry, Jul-19, Volume: 44, Issue:15
ElogD(oct): a tool for lipophilicity determination in drug discovery. 2. Basic and neutral compounds.
AID19262Aqueous solubility2000Bioorganic & medicinal chemistry letters, Jun-05, Volume: 10, Issue:11
Prediction of drug solubility from Monte Carlo simulations.
AID26362Ionization constant (pKa)2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
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.
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.
AID386623Inhibition of 4-(4-(dimethylamino)styryl)-N-methylpyridinium uptake at human OCT1 expressed in HEK293 cells at 100 uM by confocal microscopy2008Journal of medicinal chemistry, Oct-09, Volume: 51, Issue:19
Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1.
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.
AID8002Observed volume of distribution2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
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.
AID114498Compound was administered subcutaneously and was evaluated for opioid agonist activity by antinociceptive tail-flick (TF) assay in mice.1984Journal of medicinal chemistry, Apr, Volume: 27, Issue:4
Racemic and optically active 2,9-dimethyl-5-(m-hydroxyphenyl)morphans and pharmacological comparison with the 9-demethyl homologues.
AID1136228Analgesic activity in Sprague-Dawley rat normal foot assessed as response threshold at 16 to 32 mg/kg, po1978Journal of medicinal chemistry, Sep, Volume: 21, Issue:9
Synthesis and analgesic activity of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones and 3-(substituted phenyl)-1,2,3-triazolo[4,5-b]pyridines.
AID26304Partition coefficient (logD6.5)2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID624616Specific activity of expressed human recombinant UGT2B152000Annual review of pharmacology and toxicology, , Volume: 40Human UDP-glucuronosyltransferases: metabolism, expression, and disease.
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.
AID228905Effective dose required to produce analgesic activity in the trypsin hyperalgesia assay by oral administration2003Journal of medicinal chemistry, Jan-30, Volume: 46, Issue:3
Indanylidenes. 1. Design and synthesis of (E)-2-(4,6-difluoro-1-indanylidene)acetamide, a potent, centrally acting muscle relaxant with antiinflammatory and analgesic activity.
AID624640Drug glucuronidation reaction catalyzed by human recombinant UGT2B72005Pharmacology & therapeutics, Apr, Volume: 106, Issue:1
UDP-glucuronosyltransferases and clinical drug-drug interactions.
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.
AID604022Fraction unbound in Sprague-Dawley rat plasma administered in casettes of 2/3 drugs at 4 hr constant rate intravenous infusions using flow rate of 1 (ml/kg)/hr corresponding to dosage rate of 2 (umol/kg)/hr by LC-MS/MS method2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
Structure-brain exposure relationships in rat and human using a novel data set of unbound drug concentrations in brain interstitial and cerebrospinal fluids.
AID311367Permeability coefficient in human skin2007Bioorganic & medicinal chemistry, Nov-15, Volume: 15, Issue:22
Transdermal penetration behaviour of drugs: CART-clustering, QSPR and selection of model compounds.
AID19240Partition coefficient of Zwitterion (logD)1996Journal of medicinal chemistry, Oct-25, Volume: 39, Issue:22
Octanol-, chloroform-, and propylene glycol dipelargonat-water partitioning of morphine-6-glucuronide and other related opiates.
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID183317Anti-inflammatory effect expressed as % inhibition at 50 mg/kg in acute carrageenan paw edema test in rats1993Journal of medicinal chemistry, Feb-19, Volume: 36, Issue:4
Novel nonopioid non-antiinflammatory analgesics: 3-(aminoalkyl)- and 3-[(4-aryl-1-piperazinyl)alkyl]oxazolo[4,5-b]pyridin-2(3H)-ones.
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID178138Compound was tested for analgesic activity by tail-flick assay in rat after subcutaneous administration1981Journal of medicinal chemistry, Jun, Volume: 24, Issue:6
Analgesic narcotic antagonists. 6. 7 beta, 8 beta-Methano- and 7 beta, 8 beta-epoxydihydrocodeinone.
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.
AID427370Anxiolytic-like activity in Dunkin-Hartley guinea pig assessed as reduction in number of separation-induced vocalizations at 0.3 mg/kg, po after 2 hrs by guinea pig pup vocalization assay2009Journal of medicinal chemistry, Sep-10, Volume: 52, Issue:17
Discovery of orally active 3-pyridinyl-tropane as a potent nociceptin receptor agonist for the management of cough.
AID1222793Dissociation constant, pKa of the compound2013Drug metabolism and disposition: the biological fate of chemicals, May, Volume: 41, Issue:5
Which metabolites circulate?
AID178161Antagonist activity in rat tail flick assay by subcutaneous administration1980Journal of medicinal chemistry, Dec, Volume: 23, Issue:12
Analgesic narcotic antagonists. 4. 7-Methyl-N-(cycloalkylmethyl)-3-hydroxymorphinan-6-ones and -isomorphinan-6-ones.
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.
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]
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID1526732Substrate activity at human OCT1 expressed in HEK293 cells assessed as increase in compound uptake at 0.1 uM incubated for 2 mins by LC-MS/MS analysis relative to control empty vector transfected cells2019Journal of medicinal chemistry, 11-14, Volume: 62, Issue:21
Opioids as Substrates and Inhibitors of the Genetically Highly Variable Organic Cation Transporter OCT1.
AID180157Effective dose was measured by using rat tail flick assay after subcutaneous administration1980Journal of medicinal chemistry, Feb, Volume: 23, Issue:2
Analgesic narcotic antagonists. 2. 8-Alkymorphinan-6-ones.
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]
AID114495Compound was administered subcutaneously and was evaluated for opioid agonist activity by antinociceptive p-phenylquinone-writhing (PPQ) assay in mice,1984Journal of medicinal chemistry, Apr, Volume: 27, Issue:4
Racemic and optically active 2,9-dimethyl-5-(m-hydroxyphenyl)morphans and pharmacological comparison with the 9-demethyl homologues.
AID25846Amine pKa of compound1996Journal of medicinal chemistry, Oct-25, Volume: 39, Issue:22
Octanol-, chloroform-, and propylene glycol dipelargonat-water partitioning of morphine-6-glucuronide and other related opiates.
AID624620Specific activity of expressed human recombinant UGT2B7H2000Annual review of pharmacology and toxicology, , Volume: 40Human UDP-glucuronosyltransferases: metabolism, expression, and disease.
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.
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.
AID151914Binding constant for the antagonist state was measured for its ability to displace [3H]naloxone from opioid mu 1 receptor buffered homogenate of rat brain membranes1988Journal of medicinal chemistry, Mar, Volume: 31, Issue:3
Structure-activity relationships for drugs binding to the agonist and antagonist states of the primary morphine receptor.
AID29811Oral bioavailability in human2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID377382Antitussive activity in ammonia liquor-induced mouse assessed as number of cough times at 10 mg/kg, po daily for 3 consecutive days administered before ammonia liquor induction measured for 3 mins2005Journal of natural products, Feb, Volume: 68, Issue:2
Steroidal alkaloids from the bulbs of Fritillaria puqiensis.
AID108541Compound was administered subcutaneously and was evaluated for opioid antagonist activity (versus morphine) by tail-flick (TF) antagonism test; I denotes Inactive at 30 mg/kg1984Journal of medicinal chemistry, Apr, Volume: 27, Issue:4
Racemic and optically active 2,9-dimethyl-5-(m-hydroxyphenyl)morphans and pharmacological comparison with the 9-demethyl homologues.
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.
AID147865In vitro binding affinity against cloned human Opioid receptor kappa 1 expressed in HEK 293S cells2003Journal of medicinal chemistry, Jan-02, Volume: 46, Issue:1
The power of visual imagery in drug design. Isopavines as a new class of morphinomimetics and their human opioid receptor binding activity.
AID1136225Analgesic activity in Sprague-Dawley rat brewer's yeast treated foot assessed as response threshold at 8 to 16 mg/kg, po1978Journal of medicinal chemistry, Sep, Volume: 21, Issue:9
Synthesis and analgesic activity of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones and 3-(substituted phenyl)-1,2,3-triazolo[4,5-b]pyridines.
AID131018Analgesic agonist activity in acetic acid induced mouse writhing assay, subcutaneous administration1981Journal of medicinal chemistry, Jun, Volume: 24, Issue:6
Analgesic narcotic antagonists. 5. 7,7-Dimethyldihydrocodeinones and 7,7-dimethyldihydromorphinones.
AID1137105Analgesic activity in sc dosed mouse by hot plate method1977Journal of medicinal chemistry, Aug, Volume: 20, Issue:8
Pyrrole esters of tropanols and related structures as analgesics.
AID1146145Analgesic activity in sc dosed mouse by hot-plate assay1977Journal of medicinal chemistry, Nov, Volume: 20, Issue:11
Heterocyclic and piperonylic acid esters of 1-methyl-4-piperidinol as analgesics.
AID1209583Unbound drug partitioning coefficient, Kp of the compound assessed as ratio of unbound concentration in Sprague-Dawley rat brain to unbound concentration in plasma2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Measurement of unbound drug exposure in brain: modeling of pH partitioning explains diverging results between the brain slice and brain homogenate methods.
AID18980Log D of compound; LogD at pH 7.41996Journal of medicinal chemistry, Oct-25, Volume: 39, Issue:22
Octanol-, chloroform-, and propylene glycol dipelargonat-water partitioning of morphine-6-glucuronide and other related opiates.
AID132480Analgesic activity in mouse1980Journal of medicinal chemistry, Mar, Volume: 23, Issue:3
Third Smissman Award address: reminiscences and musings of a classical medicinal chemist.
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID1137221Analgesic activity in mouse by Eddy hot-plate method1978Journal of medicinal chemistry, Feb, Volume: 21, Issue:2
Synthesis and analgetic activity of 1,2,3,4,5,6-hexahydro-1,6-methano-3-benzozocines.
AID132133The effective dose was measured by using mouse writhing assay after the compound administered subcutaneously.1980Journal of medicinal chemistry, Feb, Volume: 23, Issue:2
Analgesic narcotic antagonists. 2. 8-Alkymorphinan-6-ones.
AID234027The sodium index is the ratio of the IC50 value for the inhibition of [3H]naloxone binding to homogenates of rat brain minus cerebellum in presence of 100 mM of NaCl.1984Journal of medicinal chemistry, May, Volume: 27, Issue:5
5-Aryl-3-azabicyclo[3.2.0]heptan-6-one ketals, compounds with morphine-like analgesic activity.
AID1526733Substrate activity at human OCT1 expressed in HEK293 cells assessed as increase in compound uptake at 0.5 uM incubated for 2 mins by LC-MS/MS analysis relative to control empty vector transfected cells2019Journal of medicinal chemistry, 11-14, Volume: 62, Issue:21
Opioids as Substrates and Inhibitors of the Genetically Highly Variable Organic Cation Transporter OCT1.
AID1057815Inhibition of UDP-glucuronosyltransferase in Sprague-Dawley rat liver microsomes assessed as morphine conversion to M3G after 30 mins by HPLC analysis2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID205268Inhibition of binding of Batrachotoxinin [3H]BTX-B to high affinity sites on voltage dependent sodium channels in a vesicular preparation from guinea pig cerebral cortex at 10 uM1985Journal of medicinal chemistry, Mar, Volume: 28, Issue:3
[3H]Batrachotoxinin A 20 alpha-benzoate binding to voltage-sensitive sodium channels: a rapid and quantitative assay for local anesthetic activity in a variety of drugs.
AID19246Partition coefficient of cation (logD)1996Journal of medicinal chemistry, Oct-25, Volume: 39, Issue:22
Octanol-, chloroform-, and propylene glycol dipelargonat-water partitioning of morphine-6-glucuronide and other related opiates.
AID150244Concentration required to inhibit [3H]naltrexone binding to Opioid receptors1982Journal of medicinal chemistry, Oct, Volume: 25, Issue:10
Synthesis and pharmacology of metabolically stable tert-butyl ethers of morphine and levorphanol.
AID151006Selectivity of mu IC50 to that of delta IC50 was calculated2003Journal of medicinal chemistry, Jan-02, Volume: 46, Issue:1
The power of visual imagery in drug design. Isopavines as a new class of morphinomimetics and their human opioid receptor binding activity.
AID330424Selectivity for recombinant mu opioid receptor over recombinant kappa opioid receptor2008Journal of medicinal chemistry, Apr-10, Volume: 51, Issue:7
Opioids and efflux transporters. Part 2: P-glycoprotein substrate activity of 3- and 6-substituted morphine analogs.
AID352652Antitussive activity against capsaicin-induced cough in po dosed Hartley guinea pig model after 2 hrs2009Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9
The discovery of tropane derivatives as nociceptin receptor ligands for the management of cough and anxiety.
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID129302Antinociceptive activity by measuring inhibition of acetylcholine writhing in mouse1983Journal of medicinal chemistry, Jan, Volume: 26, Issue:1
Synthesis of exo-3-phenylbicyclo[3.2.1]oct-3-en-2-amine and related compounds as potential analgesics.
AID178144Analgesic agonist activity in heat stimulus rat tail-flick assay on subcutaneous administration1981Journal of medicinal chemistry, Jun, Volume: 24, Issue:6
Analgesic narcotic antagonists. 5. 7,7-Dimethyldihydrocodeinones and 7,7-dimethyldihydromorphinones.
AID604021Unbound volume of distribution in Sprague-Dawley rat brain measured per gram of brain tissue administered in casettes of 2/3 drugs at 4 hr constant rate intravenous infusions using flow rate of 1 (ml/kg)/hr corresponding to dosage rate of 2 (umol/kg)/hr b2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
Structure-brain exposure relationships in rat and human using a novel data set of unbound drug concentrations in brain interstitial and cerebrospinal fluids.
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.
AID1057811Inhibition of UDP-glucuronosyltransferase in Sprague-Dawley rat hepatocytes assessed as morphine conversion to M3G incubated for 72 hrs prior to substrate addition measured after 2 hrs by HPLC analysis2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID179386Concentration of drug required to inhibit the stereospecific binding of [3H]naloxone (5 nM) to homogenates of rat brain minus cerebellum in the presence of 100 mM NaCl1984Journal of medicinal chemistry, May, Volume: 27, Issue:5
5-Aryl-3-azabicyclo[3.2.0]heptan-6-one ketals, compounds with morphine-like analgesic activity.
AID330423Selectivity for recombinant mu opioid receptor over recombinant delta opioid receptor2008Journal of medicinal chemistry, Apr-10, Volume: 51, Issue:7
Opioids and efflux transporters. Part 2: P-glycoprotein substrate activity of 3- and 6-substituted morphine analogs.
AID327877Activation of human mu opioid receptor expressed in HEK293a cells co-expressing YFP-labelled alphai1 and CFP-labelled beta1gamma2 Gi subunits assessed as Gi protein activation by fluorescence resonance energy transfer2007The Journal of biological chemistry, Sep-14, Volume: 282, Issue:37
Live cell monitoring of mu-opioid receptor-mediated G-protein activation reveals strong biological activity of close morphine biosynthetic precursors.
AID1057822Activity at UDP-glucuronosyltransferase in Sprague-Dawley rat liver microsomes assessed as morphine conversion to M3G at 10 uM by Michaelis-Menten plot analysis2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID1057821Activity at UDP-glucuronosyltransferase in Sprague-Dawley rat liver microsomes assessed as morphine conversion to M3G at 50 uM by Michaelis-Menten plot analysis2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
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.
AID1135667Analgesic activity in sc dosed mouse by hot-plate method1978Journal of medicinal chemistry, Jul, Volume: 21, Issue:7
Aromatic esters of nonquaternary carbon-4 piperidinols as analgesics.
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.
AID754479Inhibition of gastrointestinal transit of charcoal meal in rat at 55.2 mg/kg, po2013Journal of medicinal chemistry, Jun-27, Volume: 56, Issue:12
Orally active opioid compounds from a non-poppy source.
AID114491Compound was administered subcutaneously and was evaluated for opioid agonist activity by antinociceptive hotplate (HP) assay in mice,1984Journal of medicinal chemistry, Apr, Volume: 27, Issue:4
Racemic and optically active 2,9-dimethyl-5-(m-hydroxyphenyl)morphans and pharmacological comparison with the 9-demethyl homologues.
AID311524Oral bioavailability in human2007Bioorganic & medicinal chemistry, Dec-15, Volume: 15, Issue:24
Hologram QSAR model for the prediction of human oral bioavailability.
AID128507Analgesic activity was determined by writhing test after subcutaneous administration in mice1982Journal of medicinal chemistry, Oct, Volume: 25, Issue:10
Synthesis and pharmacology of metabolically stable tert-butyl ethers of morphine and levorphanol.
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID128023Compound was tested for analgesia in mouse writhing assay by subcutaneous administration1980Journal of medicinal chemistry, Dec, Volume: 23, Issue:12
Analgesic narcotic antagonists. 4. 7-Methyl-N-(cycloalkylmethyl)-3-hydroxymorphinan-6-ones and -isomorphinan-6-ones.
AID1057819Clearance in Sprague-Dawley rat liver microsomes at 2.5 uM2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID427372Anxiolytic-like activity in po dosed 20 hrs water-deprived CD rat after 2 hrs by conditioned lick suppression assay2009Journal of medicinal chemistry, Sep-10, Volume: 52, Issue:17
Discovery of orally active 3-pyridinyl-tropane as a potent nociceptin receptor agonist for the management of cough.
AID624613Specific activity of expressed human recombinant UGT1A102000Annual review of pharmacology and toxicology, , Volume: 40Human UDP-glucuronosyltransferases: metabolism, expression, and disease.
AID150822In vitro binding affinity against cloned human Opioid receptor mu 1 expressed in HEK 293S cells2003Journal of medicinal chemistry, Jan-02, Volume: 46, Issue:1
The power of visual imagery in drug design. Isopavines as a new class of morphinomimetics and their human opioid receptor binding activity.
AID1057816Clearance in Sprague-Dawley rat liver microsomes at 50 uM2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID1057817Clearance in Sprague-Dawley rat liver microsomes at 5 uM2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID112942Analgesic activity in mice using p-phenylquinone test.1993Journal of medicinal chemistry, Feb-19, Volume: 36, Issue:4
Novel nonopioid non-antiinflammatory analgesics: 3-(aminoalkyl)- and 3-[(4-aryl-1-piperazinyl)alkyl]oxazolo[4,5-b]pyridin-2(3H)-ones.
AID330420Displacement of [3H]diprenorphine from recombinant mu opioid receptor expressed in C6 cells2008Journal of medicinal chemistry, Apr-10, Volume: 51, Issue:7
Opioids and efflux transporters. Part 2: P-glycoprotein substrate activity of 3- and 6-substituted morphine analogs.
AID1133600Antitussive activity in po dosed Dunkin-Hartley guinea pig assessed as inhibition of electrically-stimulated vagus nerve-induced cough administered compound prior to electrical stimulation of vagus nerve measured at 20 to 40 mins1977Journal of medicinal chemistry, Feb, Volume: 20, Issue:2
Synthesis and antitussive activity of aminotetra- (and -hexa-) hydrodibenzofurans.
AID54566Inhibition of MAMC O-dealkylation mediated by rat Cytochrome P450 2D4 expressed in Saccharomyces cerevisiae2003Journal of medicinal chemistry, Jan-02, Volume: 46, Issue:1
Homology modeling of rat and human cytochrome P450 2D (CYP2D) isoforms and computational rationalization of experimental ligand-binding specificities.
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID1526752Passive membrane permeability by LC-MS/MS analysis based PAMPA2019Journal of medicinal chemistry, 11-14, Volume: 62, Issue:21
Opioids as Substrates and Inhibitors of the Genetically Highly Variable Organic Cation Transporter OCT1.
AID126652Physical dependence capacity (PDC) of the compound; intermed physical dependence capacity1992Journal of medicinal chemistry, Oct-02, Volume: 35, Issue:20
Alfred Burger Award address. A half century in medicinal chemistry with major emphasis on pain-relieving drugs and their antagonists.
AID228904Effective dose required to produce analgesic activity in the phalanges algesia assay by oral administration2003Journal of medicinal chemistry, Jan-30, Volume: 46, Issue:3
Indanylidenes. 1. Design and synthesis of (E)-2-(4,6-difluoro-1-indanylidene)acetamide, a potent, centrally acting muscle relaxant with antiinflammatory and analgesic activity.
AID109795General behavior in mice after oral administration (750 mg/kg) using acute toxicity assay; Convulsions1993Journal of medicinal chemistry, Feb-19, Volume: 36, Issue:4
Novel nonopioid non-antiinflammatory analgesics: 3-(aminoalkyl)- and 3-[(4-aryl-1-piperazinyl)alkyl]oxazolo[4,5-b]pyridin-2(3H)-ones.
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
AID128027Compound was tested for analgesic activity by writhing assay in mouse after subcutaneous administration1981Journal of medicinal chemistry, Jun, Volume: 24, Issue:6
Analgesic narcotic antagonists. 6. 7 beta, 8 beta-Methano- and 7 beta, 8 beta-epoxydihydrocodeinone.
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.
AID243151Inhibitory concentration against potassium channel HERG2005Bioorganic & medicinal chemistry letters, Jun-02, Volume: 15, Issue:11
A discriminant model constructed by the support vector machine method for HERG potassium channel inhibitors.
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.
AID1209582Unbound volume of distribution in Sprague-Dawley rat brain slices at 100 nM after 5 hrs2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Measurement of unbound drug exposure in brain: modeling of pH partitioning explains diverging results between the brain slice and brain homogenate methods.
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.
AID604023Ratio of total drug level in brain to plasma in Sprague-Dawley rat administered in casettes of 2/3 drugs at 4 hr constant rate intravenous infusions using flow rate of 1 (ml/kg)/hr corresponding to dosage rate of 2 (umol/kg)/hr by LC-MS/MS method2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
Structure-brain exposure relationships in rat and human using a novel data set of unbound drug concentrations in brain interstitial and cerebrospinal fluids.
AID54562Inhibition of MAMC O-dealkylation mediated by rat Cytochrome P450 2D1 expressed in Saccharomyces cerevisiae2003Journal of medicinal chemistry, Jan-02, Volume: 46, Issue:1
Homology modeling of rat and human cytochrome P450 2D (CYP2D) isoforms and computational rationalization of experimental ligand-binding specificities.
AID427367Antitussive activity against po dosed capsaicin-induced guinea pig cough model administered 15 mins before capsaicin challenge measured after 2 hrs2009Journal of medicinal chemistry, Sep-10, Volume: 52, Issue:17
Discovery of orally active 3-pyridinyl-tropane as a potent nociceptin receptor agonist for the management of cough.
AID7783Unbound fraction (plasma)2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
AID1057820Clearance in Sprague-Dawley rat liver microsomes at 1 uM2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID126331Analgesic activity in monkeys.1992Journal of medicinal chemistry, Oct-02, Volume: 35, Issue:20
Alfred Burger Award address. A half century in medicinal chemistry with major emphasis on pain-relieving drugs and their antagonists.
AID1057823Activity at UDP-glucuronosyltransferase in Sprague-Dawley rat liver microsomes assessed as morphine conversion to M3G at 5 uM by Michaelis-Menten plot analysis2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID604020Unbound drug concentration in Sprague-Dawley rat plasma administered in casettes of 2/3 drugs at 4 hr constant rate intravenous infusions using flow rate of 1 (ml/kg)/hr corresponding to dosage rate of 2 (umol/kg)/hr by LC-MS/MS method2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
Structure-brain exposure relationships in rat and human using a novel data set of unbound drug concentrations in brain interstitial and cerebrospinal fluids.
AID178325Compound was tested for antinociceptive activity in heat stimulus rat tail flick assay after subcutaneous administration of the drug1981Journal of medicinal chemistry, Dec, Volume: 24, Issue:12
Analgesic narcotic antagonists. 8. 7 alpha-Alkyl-4,5 alpha-epoxymorphinan-6-ones.
AID330418Effect on human recombinant Pgp-mediated ATP consumption assessed as increase in ATPase activity at 200 uM by Pgp-Glo assay2008Journal of medicinal chemistry, Apr-10, Volume: 51, Issue:7
Opioids and efflux transporters. Part 2: P-glycoprotein substrate activity of 3- and 6-substituted morphine analogs.
AID1146147Analgesic activity in sc dosed mouse by Nilsen method1977Journal of medicinal chemistry, Nov, Volume: 20, Issue:11
Heterocyclic and piperonylic acid esters of 1-methyl-4-piperidinol as analgesics.
AID624608Specific activity of expressed human recombinant UGT1A42000Annual review of pharmacology and toxicology, , Volume: 40Human UDP-glucuronosyltransferases: metabolism, expression, and disease.
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.
AID624611Specific activity of expressed human recombinant UGT1A82000Annual review of pharmacology and toxicology, , Volume: 40Human UDP-glucuronosyltransferases: metabolism, expression, and disease.
AID604026Unbound CSF to plasma concentration ratio in human2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
Structure-brain exposure relationships in rat and human using a novel data set of unbound drug concentrations in brain interstitial and cerebrospinal fluids.
AID1135668Analgesic activity in sc dosed mouse by Nilsen method1978Journal of medicinal chemistry, Jul, Volume: 21, Issue:7
Aromatic esters of nonquaternary carbon-4 piperidinols as analgesics.
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.
AID117605Percent mortality in mice after oral administration (750 mg/kg) using acute toxicity assay1993Journal of medicinal chemistry, Feb-19, Volume: 36, Issue:4
Novel nonopioid non-antiinflammatory analgesics: 3-(aminoalkyl)- and 3-[(4-aryl-1-piperazinyl)alkyl]oxazolo[4,5-b]pyridin-2(3H)-ones.
AID128214Narcotic agonistic activity in acetic acid mouse writhing assay after subcutaneous administration of the drug1981Journal of medicinal chemistry, Dec, Volume: 24, Issue:12
Analgesic narcotic antagonists. 8. 7 alpha-Alkyl-4,5 alpha-epoxymorphinan-6-ones.
AID1137110Analgesic activity in sc dosed mouse by Nilsen method1977Journal of medicinal chemistry, Aug, Volume: 20, Issue:8
Pyrrole esters of tropanols and related structures as analgesics.
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.
AID178670Antinociceptive activity by measuring in flamed paw pressure threshold in rat1983Journal of medicinal chemistry, Jan, Volume: 26, Issue:1
Synthesis of exo-3-phenylbicyclo[3.2.1]oct-3-en-2-amine and related compounds as potential analgesics.
AID1133599Antitussive activity in Dunkin-Hartley guinea pig assessed as inhibition of electrically-stimulated vagus nerve-induced cough at 100 mg/kg, po administered compound prior to electrical stimulation of vagus nerve measured at 20 to 40 mins relative to contr1977Journal of medicinal chemistry, Feb, Volume: 20, Issue:2
Synthesis and antitussive activity of aminotetra- (and -hexa-) hydrodibenzofurans.
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.
AID148090In vitro binding affinity against cloned human Opioid receptor delta 1 expressed in HEK 293S cells2003Journal of medicinal chemistry, Jan-02, Volume: 46, Issue:1
The power of visual imagery in drug design. Isopavines as a new class of morphinomimetics and their human opioid receptor binding activity.
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]
AID1057824Activity at UDP-glucuronosyltransferase in Sprague-Dawley rat liver microsomes assessed as morphine conversion to M3G at 2.5 uM by Michaelis-Menten plot analysis2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
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]
AID22293Delta logD (logD6.5 - logD7.4)2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID1057813Inhibition of UDP-glucuronosyltransferase in Sprague-Dawley rat liver microsomes assessed as morphine conversion to M6G after 30 mins by HPLC analysis2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID233518Antagonistic potency was evaluated as analgesic activity in presence of nalorphine; No1980Journal of medicinal chemistry, Mar, Volume: 23, Issue:3
Third Smissman Award address: reminiscences and musings of a classical medicinal chemist.
AID1653001Antitussive activity in ammonia aerosol-stimulated Kunming mouse assessed as inhibition of number of cough administered as po dose 1 hr before ammonia aerosol stimulation (Rvb = 42 No_unit)2019European journal of medicinal chemistry, Feb-15, Volume: 164Recent applications of hydantoin and thiohydantoin in medicinal chemistry.
AID604025Unbound CSF to plasma concentration ratio in Sprague-Dawley rat administered in casettes of 2/3 drugs at 4 hr constant rate intravenous infusions using flow rate of 1 (ml/kg)/hr corresponding to dosage rate of 2 (umol/kg)/hr by LC-MS/MS method2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
Structure-brain exposure relationships in rat and human using a novel data set of unbound drug concentrations in brain interstitial and cerebrospinal fluids.
AID1526751Inhibition of human OCT1 expressed in HEK293 cells assessed as reduction in ASP+ substrate uptake by microplate reader based analysis2019Journal of medicinal chemistry, 11-14, Volume: 62, Issue:21
Opioids as Substrates and Inhibitors of the Genetically Highly Variable Organic Cation Transporter OCT1.
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.
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.
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID1209581Fraction unbound in Sprague-Dawley rat brain homogenates at 5 uM by equilibrium dialysis analysis2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Measurement of unbound drug exposure in brain: modeling of pH partitioning explains diverging results between the brain slice and brain homogenate methods.
AID179385Concentration of drug required to inhibit the stereospecific binding of [3H]-naloxone (5 nM) to homogenates of rat brain minus cerebellum in the absence of 100 mM NaCl1984Journal of medicinal chemistry, May, Volume: 27, Issue:5
5-Aryl-3-azabicyclo[3.2.0]heptan-6-one ketals, compounds with morphine-like analgesic activity.
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.
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID128505Analgesic activity was determined by tail flick assay after subcutaneous administration in mice1982Journal of medicinal chemistry, Oct, Volume: 25, Issue:10
Synthesis and pharmacology of metabolically stable tert-butyl ethers of morphine and levorphanol.
AID228903Effective dose required to produce analgesic activity in the adjuvant arthritis hyperalgesia assay by oral administration2003Journal of medicinal chemistry, Jan-30, Volume: 46, Issue:3
Indanylidenes. 1. Design and synthesis of (E)-2-(4,6-difluoro-1-indanylidene)acetamide, a potent, centrally acting muscle relaxant with antiinflammatory and analgesic activity.
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.
AID327878Displacement of [3H]naloxone from human mu poioid receptor expressed in HEK293 cells2007The Journal of biological chemistry, Sep-14, Volume: 282, Issue:37
Live cell monitoring of mu-opioid receptor-mediated G-protein activation reveals strong biological activity of close morphine biosynthetic precursors.
AID173386Behavioral stimulant activity in rat by peroral administration; Inactive1983Journal of medicinal chemistry, Jan, Volume: 26, Issue:1
Synthesis of exo-3-phenylbicyclo[3.2.1]oct-3-en-2-amine and related compounds as potential analgesics.
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]
AID1057818Clearance in Sprague-Dawley rat liver microsomes at 10 uM2013Bioorganic & medicinal chemistry, Dec-15, Volume: 21, Issue:24
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat.
AID127137Physical dependence capacity at abstinence suppressant dose; Intermediate1980Journal of medicinal chemistry, Mar, Volume: 23, Issue:3
Third Smissman Award address: reminiscences and musings of a classical medicinal chemist.
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.
AID624607Specific activity of expressed human recombinant UGT1A32000Annual review of pharmacology and toxicology, , Volume: 40Human UDP-glucuronosyltransferases: metabolism, expression, and disease.
AID1124317Analgesic activity in sc dosed mouse by eddy's hot-plate method1979Journal of medicinal chemistry, Apr, Volume: 22, Issue:4
Synthesis and pharmacological activity of 2,3,4,5,-tetrahydro-1,5-methano-1H-3-benzazepines.
AID352476Antitussive activity in po dosed guinea pig GPPV model assessed as reduction of capsaicin-induced coughing after 2 hrs administered 15 mins before capsaicin challenge2009Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9
Identification of 3-substituted N-benzhydryl-nortropane analogs as nociceptin receptor ligands for the management of cough and anxiety.
AID23717Partition coefficient (logP)1988Journal of medicinal chemistry, Mar, Volume: 31, Issue:3
Structure-activity relationships for drugs binding to the agonist and antagonist states of the primary morphine receptor.
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID1149090Analgesic activity in po dosed mouse by Nilsen assay1976Journal of medicinal chemistry, Mar, Volume: 19, Issue:3
Optical resolution of (+/-)-2,5-dimethyl-2'-hydroxy-9alpha- and -9beta-propyl-6,7-benzomorphans and their pharmacological properties.
AID352654Anxiolytic activity in Dunkin-Hartley guinea pig pup assessed as reduction in number of vocalization produced due to separation measured after 2 hrs2009Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9
The discovery of tropane derivatives as nociceptin receptor ligands for the management of cough and anxiety.
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID29359Ionization constant (pKa)2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID781328pKa (acid-base dissociation constant) as determined by Luan ref: Pharm. Res. 20052014Pharmaceutical research, Apr, Volume: 31, Issue:4
Comparison of the accuracy of experimental and predicted pKa values of basic and acidic compounds.
AID352653Anxiolytic activity in po dosed CD rats assessed as suppression of conditioned paw licking administered twice per day for 14 days measured after 2 hrs of last dose2009Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9
The discovery of tropane derivatives as nociceptin receptor ligands for the management of cough and anxiety.
AID54570Inhibition of MAMC O-dealkylation mediated by human Cytochrome P450 2D6 expressed in human lymphoblastoid cell line2003Journal of medicinal chemistry, Jan-02, Volume: 46, Issue:1
Homology modeling of rat and human cytochrome P450 2D (CYP2D) isoforms and computational rationalization of experimental ligand-binding specificities.
AID54565Inhibition of MAMC O-dealkylation mediated by rat Cytochrome P450 2D3 expressed in Saccharomyces cerevisiae2003Journal of medicinal chemistry, Jan-02, Volume: 46, Issue:1
Homology modeling of rat and human cytochrome P450 2D (CYP2D) isoforms and computational rationalization of experimental ligand-binding specificities.
AID54564Inhibition of MAMC O-dealkylation mediated by rat Cytochrome P450 2D2 expressed in Saccharomyces cerevisiae2003Journal of medicinal chemistry, Jan-02, Volume: 46, Issue:1
Homology modeling of rat and human cytochrome P450 2D (CYP2D) isoforms and computational rationalization of experimental ligand-binding specificities.
AID1346364Human mu receptor (Opioid receptors)1998NIDA research monograph, Mar, Volume: 178Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications.
AID1802709PRESTO-Tango Assay from Article 10.1038/nchembio.2334: \\In silico design of novel probes for the atypical opioid receptor MRGPRX2.\\2017Nature chemical biology, 05, Volume: 13, Issue:5
In silico design of novel probes for the atypical opioid receptor MRGPRX2.
AID1802708Intracellular Calcium Mobilization Assay from Article 10.1038/nchembio.2334: \\In silico design of novel probes for the atypical opioid receptor MRGPRX2.\\2017Nature chemical biology, 05, Volume: 13, Issue:5
In silico design of novel probes for the atypical opioid receptor MRGPRX2.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (4,394)

TimeframeStudies, This Drug (%)All Drugs %
pre-19902121 (48.27)18.7374
1990's646 (14.70)18.2507
2000's604 (13.75)29.6817
2010's778 (17.71)24.3611
2020's245 (5.58)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 125.59

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 Index125.59 (24.57)
Research Supply Index8.62 (2.92)
Research Growth Index4.52 (4.65)
Search Engine Demand Index242.10 (26.88)
Search Engine Supply Index2.03 (0.95)

This Compound (125.59)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials730 (15.16%)5.53%
Reviews247 (5.13%)6.00%
Case Studies354 (7.35%)4.05%
Observational20 (0.42%)0.25%
Other3,464 (71.94%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (77)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Absorption and Metabolism of Oral Codeine in Mechanically Ventilated Neonates [NCT01322204]Phase 16 participants (Actual)Interventional2008-08-31Completed
COMPARISON OF EFFICACY OF DICLOFENAC VERSUS DICLOFENAC PLUS CODEINE AND DICLOFENAC PLUS LACOSAMIDE IN ACUTE SCIATICA [NCT05626140]Phase 3120 participants (Actual)Interventional2021-09-28Completed
Post-operative Pain Control After Photorefractive Keratectomy Comparing Acetaminophen/Codeine vs Acetaminophen/Oxycodone [NCT04399122]Phase 4200 participants (Actual)Interventional2017-03-21Completed
Efficacy and Security of Combined Analgesia (Opioid and Anti-inflammatory Agent) to Control Pain in Children Seen in the Emergency Department for a Trauma of a Limb [NCT01189773]Phase 4200 participants (Actual)Interventional2008-02-29Completed
Paracetamol With or Without Ketoprofen in the Management of Pain During Hospitalisation and at Home for Patients Receiving Brachytherapy: Phase-2 Randomized Study [NCT02439034]Phase 2120 participants (Anticipated)Interventional2015-02-28Recruiting
Gabapentin for Pain Control After Osmotic Dilator Insertion and Prior to D&E Procedure: a Randomized Controlled Trial [NCT03080493]Phase 4121 participants (Actual)Interventional2017-03-20Completed
A Clinical, Multicenter, Randomized, Parallel-group, Double-blind, Double-dummy, Comparative Study of Non-inferiority of the Fixed Dose Combination of Codeine 30 mg/Dipyrone 500 mg From Eurofarma Versus Tylex® (Codeine 30 mg/Paracetamol 500 mg) in the Tre [NCT04972292]Phase 3288 participants (Anticipated)Interventional2023-11-08Recruiting
Efficacy of Intravenous Naproksen Sodium+Codein and Paracetamol+Codein on Postoperative Pain and Contramal Consumption After a Lumbar Disk Surgery [NCT02252614]Phase 475 participants (Anticipated)Interventional2014-09-30Not yet recruiting
The Effect of Naproxen Sodium + Codeine, and Paracetamol+ Codeine on Postoperative Laminectomy Pain [NCT02255955]Phase 475 participants (Anticipated)Interventional2014-10-31Not yet recruiting
Randomized, Double-blind and Placebo-controlled Evaluation of Efficacy and Safety of Naproxen Sodium and Codeine Phosphate Combination in Osteoarthritis [NCT02501564]Phase 4135 participants (Actual)Interventional2013-05-31Completed
A COMPARATIVE STUDY BETWEEN TWO PHARMACOLOGICAL ASSOCIATIONS OXYCODONE/NALOXONE AND CODEINE / PARACETAMOL IN TREATMENT OF MODERATE-SEVERE CHRONIC PAIN DUE TO OSTEOARTHRITIS OF KNEE AND/OR HIP [NCT02032927]Phase 40 participants (Actual)Interventional2013-06-30Withdrawn
An Open, Randomised, Multicentre Study to Compare Buprenorphine Transdermal Delivery System (BTDS) With Standard Treatment in Elderly Subjects With OA of the Hip and/or Knee [NCT00324038]Phase 4219 participants (Actual)Interventional2006-03-31Completed
Minimizing Narcotic Analgesics After Thyroid or Parathyroid Surgery [NCT03469310]Phase 4126 participants (Actual)Interventional2018-03-09Completed
Effect of Codeine on Pharyngeal and Esophageal Motility in Healthy Subjects: a Double-blind, Placebo-controlled, Randomized, Cross-over Study [NCT03784105]Phase 422 participants (Actual)Interventional2017-09-07Completed
Comparing the Efficacy of Five Oral Analgesics for Treatment of Acute Musculoskeletal Extremity Pain in the Emergency Department [NCT03173456]Phase 2600 participants (Actual)Interventional2017-11-28Completed
A Multicenter, Double-blind, Randomized, Placebo-controlled Study of Weight-Reduction and/or Low Sodium Diet Plus Acetazolamide vs Diet Plus Placebo in Subjects With Idiopathic Intracranial Hypertension With Mild Visual Loss [NCT01003639]Phase 2/Phase 3165 participants (Actual)Interventional2010-01-31Completed
An Open-Label, Randomized, Multiple-Dose, 2-Way Crossover Comparative Bioavailability Steady State Study of Codeine Phosphate/Guaifenesin Extended-Release Tablet in Healthy Subjects [NCT02572375]Phase 138 participants (Actual)Interventional2014-10-31Completed
Evaluation of Two Pharmacological Protocols for Pre-emptive Analgesia in Impacted Third Molar Surgery [NCT02665533]18 participants (Actual)Interventional2016-01-31Completed
A Phase III Randomized, Double-Blind, Placebo- and Active-Comparator-Controlled Multiple-Dose Clinical Trial to Study the Efficacy and Safety of MK0663/Etoricoxib 90 and 120 mg, Ibuprofen 600 mg, and Acetaminophen 600 mg/Codeine 60 mg in the Treatment of [NCT00694369]Phase 3588 participants (Actual)Interventional2008-06-30Completed
A Randomized Study of Codeine Plus Paracetamol Versus Placebo for PRK Post-operative Pain [NCT02625753]Phase 340 participants (Actual)Interventional2014-11-30Completed
A Randomised, Open-label, Three-treatment, Single Dose, Crossover Study Investigating the Bioequivalence of Co-codamol 15/500mg Capsules With a Co-codamol 30/500mg Tablet in Healthy Subjects Under Fasting Conditions [NCT03280095]Phase 150 participants (Actual)Interventional2014-09-23Completed
An Open-Label, Single-Dose, Crossover Comparative Bioavailability and Pharmacokinetic Study of Codeine Phosphate/Guaifenesin Extended-Release Tablet With Immediate-Release Tablet [NCT02157649]Phase 126 participants (Actual)Interventional2014-06-30Completed
A Single Dose, 3-Period, 3-Treatment, 6-Sequence Crossover Pharmacokinetic and Comparative Bioavailability Study of Codeine Sulfate Tablet Formulations Under Fasting Conditions [NCT01010139]18 participants (Actual)Interventional2006-08-31Completed
Metoclopramide and Diphenhydramine (MAD): A Cost Effective Treatment for Headache in Pregnancy When Acetaminophen Alone is Ineffective (MAD Headache Study) [NCT02295280]70 participants (Actual)Interventional2012-01-31Completed
Celecoxib vs. Acetaminophen-codeine-caffeine for Postoperative Pain in Primary Elective Open Septorhinoplasty With Osteotomies: a Randomized Controlled Trial. [NCT04259333]Phase 460 participants (Anticipated)Interventional2020-03-01Recruiting
Comparison of Two Combinations of Opioid and Non-opioid Analgesics for Acute Periradicular Abscess: A Randomized Clinical Trial [NCT02750696]27 participants (Actual)Interventional2013-04-30Completed
A Single Dose, 2-Period, 2-Treatment, 2-Way Crossover Bioequivalency Study of Codeine Sulfate Tablets Under Fasting and Fed Conditions [NCT01009892]Phase 136 participants (Actual)Interventional2008-01-31Completed
A Two Part Protocol Using Double Blind Placebo Control to Assess the Safety, Tolerability, and Pharmacokinetics of Single Escalating Intra-articular Doses Followed by Assessment of Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Intra-arti [NCT02845271]Phase 2104 participants (Actual)Interventional2016-07-21Completed
Analgesic Effect of Ibuprofen 400, 600 and 800 mg, Paracetamol 500 and 1000 mg, and Paracetamol 1000 mg Plus 60 mg Codeine: Single-dose, Randomized, Placebo-controlled and Double-blind Study on Acute Pain After Third Molar Surgery [NCT00699114]Phase 4350 participants (Anticipated)Interventional2007-06-30Completed
Analgesic Effect of Ibuprofen 400 mg/Paracetamol 1000 mg, Ibuprofen 400 mg/ Paracetamol 1000 mg/60 mg Codeine, and Paracetamol 1000 mg/Codeine 60 mg: A Single-dose, Randomized, Placebo-controlled and Double-blind Study [NCT00921700]Phase 4200 participants (Actual)Interventional2009-06-30Completed
Randomized Control Trial. Comparative Effectiveness Study for Surgery vs. Non-Surgery in Patients With Low Back Pain [NCT02883569]1,102 participants (Actual)Interventional2016-09-30Completed
Placebo-controlled Crossover Study of the Ability of Naloxegol to Reverse Opioid Effect on Colonic Motor Patterns in Healthy Volunteers [NCT05770960]Phase 415 participants (Actual)Interventional2018-06-27Completed
Effect of Preoperative Acetaminophen-Codeine-Caffeine Combination on Inferior Alveolar Nerve Block Success in Patients With Symptomatic Irreversible Pulpitis: Randomized Double-blind Controlled Trial [NCT04202406]69 participants (Actual)Interventional2021-01-09Completed
A Phase I Randomized, Double-Blinded, Placebo-Controlled Study of the Effect of Naloxegol on Gastric, Small Bowel, and Colonic Transit in Healthy Subjects [NCT02737059]Phase 172 participants (Actual)Interventional2016-07-01Completed
A Single Dose, 3-Period, 3-Treatment, 6-Sequence, 3-Way Crossover Study of the Dose Linearity of Codeine Sulfate Tablets Under Fasting Conditions [NCT01009697]Phase 134 participants (Actual)Interventional2008-03-31Completed
A Single Dose, 1-Period, 1-Treatment Study of Codeine Sulfate 15 mg Tablets Under Steady State Conditions [NCT01009853]Phase 134 participants (Actual)Interventional2008-01-31Completed
Comparison of Post-operative Analgesic Effects of Naproxen Sodium and Naproxen Sodium-codeine Phosphate Administered Preemptively for Arthroscopic Meniscus Surgery [NCT01952652]Phase 461 participants (Actual)Interventional2013-01-31Completed
A Randomized, Open-Label, 3-Period Crossover Study to Evaluate the Effect of Multiple Doses of DVS SR and Paroxetine on the CYP2D6 Biotransformation of Codeine to Morphine in Healthy Subjects. [NCT00456898]Phase 140 participants Interventional2007-01-31Completed
A Single Dose, 2-Period, 2-Treatment, 2-Way Crossover Comparative Bioavailability Study fo Codeine 30 mg Tablets and Tylenol #3 Tablets Under Fasting Conditions [NCT01010152]Phase 134 participants (Actual)Interventional2008-01-31Completed
A Single Dose Bioequivalence Study of Test Product (One Tablet of Paracetamol 1000 mg + Codeine 30 mg, Manufactured by A.C.R.A.F. S.p.A.) vs. Two Tablets of the Reference Product (Paracetamol 500 mg + Codeine 30 mg) in Healthy Volunteers [NCT02902666]Phase 146 participants (Actual)Interventional2016-04-30Completed
Effectiveness of Non-steroidal Anti-inflammatory Diclofenac and Its Association to the Opioid Codeine for Pain, Swelling and Trismus in the Bilateral Mandibular Third Molar Extraction With a High Degree of Difficulty Model. [NCT02547896]Phase 450 participants (Actual)Interventional2014-09-30Completed
A Double-blind, Double-dummy, Parallel Group, Randomised Study to Compare the Efficacy & Tolerability of Oxycodone/Naloxone Prolonged Release (OXN PR) & Codeine/Paracetamol in the Treatment of Moderate to Severe Chronic Low Back Pain or Pain Due to Osteoa [NCT00784810]Phase 4247 participants (Actual)Interventional2009-02-28Completed
A Double-blind, 5 Parallel-group, Placebo-controlled, Randomised, Single Dose, 3-site Study to Compare the Analgesic Efficacy and Tolerability of a Combination of Ibuprofen 400 mg Plus Paracetamol 1000 mg; a Combination of Ibuprofen 200 mg Plus Paracetamo [NCT01229449]Phase 3678 participants (Actual)Interventional2009-01-31Completed
Non-Invasive Assessment of Opioid Analgesia in Children With Sickle Cell Disease [NCT00513864]Phase 40 participants (Actual)Interventional2006-11-30Withdrawn(stopped due to lack of funding)
Pilot Study, Blinded Randomized Control Trial, Single Center Study to Compare Acetaminophen & Codeine Versus Ibuprofen/Acetaminophen for Pain Control and Patient Satisfaction After Ambulatory Hand Surgery [NCT02647788]Phase 4144 participants (Actual)Interventional2015-12-31Completed
Comparative Analgesic Effects of Preoperative Administration of Paracetamol (Acetominophen) 500 mg Plus Codeine 30 mg and Ibuprofen 400 mg on Pain After Third Molar Surgery [NCT04730297]Phase 4120 participants (Actual)Interventional2018-01-01Completed
A Randomized Blinded Comparison of Acetaminophen With Codeine and Ibuprofen for Treatment of Acute Pain in Children With Extremity Injuries [NCT00474721]68 participants (Actual)Interventional2002-11-30Completed
Ibuprofen Versus Acetaminophen With Codeine In Acute Pediatric Forearm Fractures [NCT00520442]335 participants (Anticipated)Interventional2003-09-30Completed
ANTERO-1: a Clinical Evaluation of an Investigational Device: the VIPUN Balloon Catheter 0.1 Used for the Evaluation of Gastric Motility [NCT03239821]22 participants (Actual)Interventional2017-09-25Completed
Chiropractic Care, Medication, and Self-Care for Neck Pain [NCT00029770]Phase 2270 participants Interventional2001-09-30Completed
An Open-label, Randomised Study Comparing the Uptake of rIL-2 in HIV-1 Infected Individuals Receiving Different Combinations of Antiemetics and Analgesic Agents During rIL-2 Dosing in ESPRIT: Toxicity Substudy of ESPRIT: TOXIL-2 Substudy [NCT00147355]Phase 328 participants (Actual)Interventional2005-11-30Terminated(stopped due to 28 of 168 patients only were enrolled, numbers too low to be conclusive)
The Effects of Cytochrome P450 2D6 Genotype on Pain Management With Codeine in Sickle Cell Disease [NCT00174538]Phase 1/Phase 260 participants (Anticipated)Interventional2005-03-31Completed
Comparison of the Efficacy of Oral Oxycodone and Oral Codeine in the Treatment of Postcraniotomy Pain [NCT01672112]Phase 440 participants (Actual)Interventional2012-07-31Completed
A Randomized, Double-Blind, Comparative Parallel Group Study of Analgesic Effectiveness and Safety of Three Different Doses of Lamaline® New Formulation vs Dafalgan® Codeine, After 10 Days Administration in Subjects With Painful Gonarthrosis. [NCT00264225]Phase 30 participants Interventional2005-12-31Completed
A Randomized Controlled Trial Comparing Combination Therapy of Acetaminophen Plus Ibuprofen Versus Tylenol #3® for the Treatment of Pain After Breast Surgery. [NCT00299039]Phase 3150 participants (Anticipated)Interventional2006-05-31Completed
Double Blind-randomized Study Comparing the Efficacy of Two Analgesia (Ixprim® and Dafalgan-Codeine®) , in the Emergency Unit. [NCT01782846]Phase 4803 participants (Actual)Interventional2011-03-31Completed
Open Label Study for the Functional Characterization of Drug Metabolism and Transport [NCT01788254]Phase 1144 participants (Actual)Interventional2012-01-31Completed
A Blinded, Randomized Controlled Trial of Opioid Analgesics for the Management of Acute Fracture Pain in Adults Discharged From the Emergency Department [NCT03478423]5 participants (Actual)Interventional2018-02-05Terminated(stopped due to Study failed to recruit in sufficient numbers and was determined to not be feasible.)
Open Label Repeated Dose Study for the Evaluation of Heritability of and Genetic Influences on Drug Pharmacokinetics (TWINS II) [NCT01845194]Phase 1117 participants (Actual)Interventional2009-12-31Completed
A Comparison of Postoperative Tramadol Versus Acetaminophen With Codeine in Children Undergoing Tonsillectomy [NCT01267136]Phase 484 participants (Actual)Interventional2011-01-31Completed
Analgesic Efficacy of Naproxen-codeine, Naproxen+Dexamethasone, and Naproxen on Myofascial Pain: A Randomized Double-blind Controlled Trial [NCT04066426]Phase 4200 participants (Actual)Interventional2018-03-01Completed
Comparing the Efficacy of Oral Opioids for Outpatient Acute Pain Management After ED Discharge [NCT01402375]Phase 3720 participants (Actual)Interventional2012-01-31Completed
Project 1 Aim 2, Adaptations of the Brain in Chronic Pain With Opioid Exposure [NCT05463367]Phase 280 participants (Anticipated)Interventional2021-01-01Recruiting
Efficacy of Preoperative Administration of Paracetamol-codeine on Pain Following Impacted Mandibular Third Molar Surgery: a Randomized, Split-mouth, Placebo-controller, Double-blind Clinical Trial [NCT03049878]Phase 432 participants (Actual)Interventional2013-02-21Completed
Human Subject Research Ethics Committee, 2 nd Affiliated Hospital, School of Medicine, Zhejiang University, China [NCT04937101]78 participants (Anticipated)Interventional2021-01-01Recruiting
Ibuprofen vs. Codeine. Is One Better for Post-operative Pain Relief Following Reduction of Paediatric Forearm Fractures? [NCT01605240]50 participants (Anticipated)Interventional2012-07-31Recruiting
An Open, Randomized, Parallel Group Study in Patients With Cancer Pain, To Compare a Two-Step Analgesic Ladder (Non-Opioid to Oxycodone) With Conventional Management Using A Three-Step Approach [NCT00378937]Phase 430 participants (Anticipated)Interventional2004-01-31Completed
Randomized, Controlled Cross-over Comparison of Cannabinoid to Oral Opioid for Postoperative Photorefractive Keratectomy Pain Control [NCT05477875]Phase 235 participants (Anticipated)Interventional2023-09-30Not yet recruiting
Double Blind Randomized Study Into the Efficacy of Codeine Phosphate Analgesia After Cleft Palate Repair in Infants [NCT00386269]Phase 444 participants (Anticipated)Interventional2004-01-31Completed
Role and Implications of Central Fatigue Limiting Aerobic Capacity in Chronic Heart Failure: The Head vs. Heart Study [NCT04332536]60 participants (Anticipated)Interventional2019-12-01Recruiting
Randomized, Open, Multicentre, National Superiority Clinical Trial to Assess the Combination of Fixed Dosage of Dipyrone and Codeine Compared to the Isolated Use of Components in the Control of Moderate to Severe Pain After Open Pelvic-abdominal Surgery. [NCT04641338]Phase 3328 participants (Anticipated)Interventional2023-03-16Recruiting
Inter- and Intra-individual Variations in Metformin Pharmacokinetics - The Importance of Genes and Drug Interactions [NCT03335423]Phase 1228 participants (Actual)Interventional2018-03-01Completed
Paracetamol Vs Paracetamol-Caffeine Association Vs Paracetamol-Codeine Association in the Management of Post Traumatic Pain in Emergencies [NCT05229965]Phase 31,500 participants (Actual)Interventional2022-11-01Completed
Comparative Efficacy of 4 Oral Analgesics for the Initial Management of Acute Musculoskeletal Extremity Pain [NCT02455518]Phase 4416 participants (Actual)Interventional2015-07-31Completed
A Multicenter, Open-Label, Safety and Pharmacokinetic Study of Oral Codeine Sulfate Administration in Pediatric Subjects 2 Years Old Through 17 Years Old With Post-procedural Pain [NCT01676493]Phase 331 participants (Actual)Interventional2012-04-30Terminated(stopped due to Decision to stop study due to low recruitment.)
Effect of Methylnaltrexone on Gastrointestinal and Colonic Transit in Health [NCT01055704]Phase 448 participants (Actual)Interventional2009-11-30Completed
A Randomised Control Clinical Trial Comparing Diclofenac / Acetaminophen /Codeine and Ibuprofen/Acetaminophen/Codeine Combination for Pain Management After Third Molars Surgery [NCT04874675]78 participants (Actual)Interventional2023-03-31Suspended(stopped due to Covid 19 lockdown)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00324038 (1) [back to overview]Average Daily Pain Scores - BS11 Pain Scores.
NCT00694369 (2) [back to overview]Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication
NCT00694369 (2) [back to overview]Total Pain Relief Score Over the First 6 Hours Post the Initial Day 1 Dose of the Study Medication (TOPAR6)
NCT00784810 (2) [back to overview]Number of Intakes of Rescue Medication (Ibuprofen) Between Visit 8 and Visit 9 for the 2 Groups.
NCT00784810 (2) [back to overview]Average Daily Pain Score Box Scale-11 (BS-11) Recorded at Week 12 (Average Pain Over Last 24 Hours)
NCT01003639 (4) [back to overview]Mean Change of Papilledema Grade on Fundus Photography
NCT01003639 (4) [back to overview]Visual Function Questionnaire (VFQ-25)
NCT01003639 (4) [back to overview]Visual Acuity (No. of Correct Letters)
NCT01003639 (4) [back to overview]Mean Change in Perimetric Mean Deviation
NCT01055704 (8) [back to overview]Colonic Geometric Center at 4 Hours
NCT01055704 (8) [back to overview]Colonic Geometric Center at 48 Hours
NCT01055704 (8) [back to overview]Stool Consistency as Reported From the Bristol Stool Scale
NCT01055704 (8) [back to overview]Stool Frequency
NCT01055704 (8) [back to overview]Colonic Filling at 6 Hours
NCT01055704 (8) [back to overview]T1/2 of Ascending Colon Emptying
NCT01055704 (8) [back to overview]T1/2 of Gastric Emptying of Solid
NCT01055704 (8) [back to overview]Colonic Geometric Center at 24 Hours
NCT01229449 (10) [back to overview]Subjects' Overall Assessment of the Study Medication Assessed at 12 Hours or Just Before Administration of Rescue Medication
NCT01229449 (10) [back to overview]Change From Baseline in Area Under the Curve (AUC) of Pain Intensity and Relief Scores (SPRID)
NCT01229449 (10) [back to overview]Change From Baseline in Peak Pain Intensity Difference (Peak PID - Ordinal)
NCT01229449 (10) [back to overview]Change From Baseline in Peak Pain Relief (PR)
NCT01229449 (10) [back to overview]Change From Baseline in AUC (0-8h) of SPRID
NCT01229449 (10) [back to overview]Change From Baseline in AUC of Individual Reading Pain Intensity and Relief Scores (SPRID)
NCT01229449 (10) [back to overview]Change From Baseline in AUC of Pain Relief Scores (TOTPAR)
NCT01229449 (10) [back to overview]Individual Pain Intensity Differences (Ordinal)
NCT01229449 (10) [back to overview]Individual Pain Intensity Differences Visual Analogue Scale (VAS)
NCT01229449 (10) [back to overview]Change From Baseline in AUC for Pain Intensity Difference Scores (SPID)
NCT01267136 (2) [back to overview]Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period.
NCT01267136 (2) [back to overview]Efficacy of Two Different Liquid Pain Medications: Tramadol vs. Codeine/Acetaminophen During the Post-tonsillectomy Recovery Period.
NCT01402375 (4) [back to overview]Overall Satisfaction With the Pain Medicine
NCT01402375 (4) [back to overview]Difference in Pain Intensity Score Before and After Last Dose.
NCT01402375 (4) [back to overview]Time to Follow up
NCT01402375 (4) [back to overview]50% or Greater Decrease in Numerical Rating Scale (NRS) Pain Score
NCT02295280 (1) [back to overview]Number of Participants With Adequate Relief of Headache as a Measure of Efficacy
NCT02455518 (2) [back to overview]Between Group Difference in Change in Numerical Rating Scale (NRS) Pain Scores
NCT02455518 (2) [back to overview]Between Group Difference in Change in Numerical Rating Scale (NRS) Pain Scores
NCT02647788 (3) [back to overview]Number of Pills Used
NCT02647788 (3) [back to overview]Quality of Recovery-9 (QoR-9).
NCT02647788 (3) [back to overview]Assessing Change in Pain Using the Visual Analogue Scale (VAS) Pain Score
NCT03080493 (6) [back to overview]Mean Change From Baseline in NRS Pain Score at Time of Presentation for D&E Procedure (Day Following Dilator Insertion)
NCT03080493 (6) [back to overview]Mean Change From Baseline in NRS Pain Score at 8 Hours After Dilator Insertion
NCT03080493 (6) [back to overview]Mean Change From Baseline in NRS Pain Score at 5 Minutes After Last Dilator Insertion
NCT03080493 (6) [back to overview]Mean Change From Baseline in NRS Pain Score at 4 Hours After Dilator Insertion
NCT03080493 (6) [back to overview]Mean Change From Baseline in NRS Pain Score at 2 Hours After Dilator Insertion
NCT03080493 (6) [back to overview]Number of Participants Using Narcotic Pain Medication (Acetaminophen/Codeine)
NCT03173456 (6) [back to overview]Change in Pain From Before Medication Administered (Baseline) to One-hour Post-baseline
NCT03173456 (6) [back to overview]Percentage of Patients Who Would Choose to Take the Study Medication Again if They Returned to the ED With Similar Pain
NCT03173456 (6) [back to overview]Percentage of Patients Who Received Rescue Medication
NCT03173456 (6) [back to overview]Percentage of Patients Who Experience Side Effects Within One Hour of Ingestion of Study Medication
NCT03173456 (6) [back to overview]Percentage of Patients Who Experience Side Effects in Two Hours After Ingestion of Study Medication
NCT03173456 (6) [back to overview]Change in Pain From Before Medication Administered (Baseline) to Two Hour Post-baseline
NCT04066426 (4) [back to overview]Pain Evaluation
NCT04066426 (4) [back to overview]Pain Evaluation
NCT04066426 (4) [back to overview]Pain Evaluation
NCT04066426 (4) [back to overview]Pain Evaluation
NCT04399122 (2) [back to overview]Post-operative Uncorrected Visual Acuity Right and Left Eye
NCT04399122 (2) [back to overview]Post-operative Average Pain Score

Average Daily Pain Scores - BS11 Pain Scores.

The primary efficacy variable was the average daily pain score recorded on a Box Scale-11 pain scale in the evening. 0 = no pain and 10 = most pain imaginable. Subjects ticked the box from 0 - 10 which best describes their level of pain. (NCT00324038)
Timeframe: every day over a 12 week study duration.

InterventionBox Scale 11 boxes (Mean)
Buprenorphine Transdermal System3
Co-codamol Tablets3

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Patient's Global Assessment of Study Medication at 24 Hours Post the Initial Day 1 Dose of the Study Medication

Patient's Global Assessment of Study Medication was on 0- to 4- point scale, with 0=Poor, and 4=Excellent for patient's rating of the study medication for pain. (NCT00694369)
Timeframe: At 24 hours post the initial Day 1 dose of the study medication

,,,,
InterventionParticipants (Number)
PoorFairGoodVery GoodExcellent
Acetaminophen 2400 mg/Codeine 240 mg11315187
Etoricoxib 120 mg75202628
Etoricoxib 90 mg1212436651
Ibuprofen 2400 mg624427335
Placebo1912553

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Total Pain Relief Score Over the First 6 Hours Post the Initial Day 1 Dose of the Study Medication (TOPAR6)

TOPAR6 was calculated by multiplying the pain relief (PR) score (0- to 4-point Likert scale, with 0=None, and 4=Complete for pain relief) at each time point by the duration (in hours) since the preceding time point, and summing these weighted values up to 6 hours post the initial Day 1 dose. The range of TOPAR6 score is 0 to 24. (NCT00694369)
Timeframe: Over the first 6 hours post the initial Day 1 dose of the study medication

InterventionUnits on a Scale (Least Squares Mean)
Placebo5.08
Etoricoxib 90 mg16.10
Etoricoxib 120 mg15.73
Ibuprofen 2400 mg15.67
Acetaminophen 2400 mg/Codeine 240 mg11.83

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Number of Intakes of Rescue Medication (Ibuprofen) Between Visit 8 and Visit 9 for the 2 Groups.

"To compare the number of intakes of rescue medication use (ibuprofen) for breakthrough pain between OXN (Oxycodone/Naloxone) and codeine/paracetamol groups. Ibuprofen tablets (400mg up to 3 times per day) were available as rescue medication. This was recorded by the subject in their diary whenever it was taken. The discrepancy in numbers of patients at this stage (between Visit 8 and Visit 9) is due to subject withdrawal during the study. The mean values presented are the number of intakes of rescue medication for this period (ie between Visit 8 and Visit 9)." (NCT00784810)
Timeframe: Between visit 8 and 9

InterventionNumber of rescue medication intakes (Mean)
Oxycodone/Naloxone Tablets (OXN)13.2
Codeine/Paracetamol Tablets9.4

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Average Daily Pain Score Box Scale-11 (BS-11) Recorded at Week 12 (Average Pain Over Last 24 Hours)

The primary objective was to demonstrate non inferiority of Oxycodone/Naloxone Prolonged Release (OXN PR) compared to codeine/paracetamol in moderate to severe pain as assessed by BS-11 average daily pain scores. The Box Scale-11 is a scale from 0 to 10 (i.e. 0, 1, 2...10), where the subject records their daily pain over the previous 24 hours, by circling the relevant box, where 0 = no pain and 10 = pain as bad as you can imagine. This value is the value recorded at week 12 (average pain over the last 24 hours) (NCT00784810)
Timeframe: Average daily pain over last 24 hours (at Week 12)

InterventionUnits on a BS-11 scale at Week 12 (Mean)
Oxycodone/Naloxone Tablets (OXN)4.2
Codeine/Paracetamol Tablets4.64

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Mean Change of Papilledema Grade on Fundus Photography

Mean change at month 6 as compared to baseline. Frisén papilledema grade is an ordinal scale that uses ocular fundus features to rate the severity of papilledema; grade 0 indicates no features of papilledema and grade 5 indicates severe papilledema. (NCT01003639)
Timeframe: Baseline and 6 Months

,
Interventionunits on a scale (Mean)
Study eyeFellow eye
Acetazolamide-1.31-1.14
Sugar Pill-0.61-0.52

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Visual Function Questionnaire (VFQ-25)

Visual Function Questionnaire (VFQ-25) total score, VFQ-25 10-item neuro-ophthalmic supplement total score: 0-100 (higher scores indicate better quality of life) (NCT01003639)
Timeframe: baseline

,
Interventionunits on a scale (Mean)
Total score10-item neuro-ophthalmic supplement
Acetazolamide83.875.8
Sugar Pill82.175.0

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Visual Acuity (No. of Correct Letters)

(NCT01003639)
Timeframe: Baseline

,
Interventioncorrect letters (Mean)
Study EyeFellow Eye
Acetazolamide56.858.3
Sugar Pill55.656.2

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Mean Change in Perimetric Mean Deviation

Treatment Effects on the Primary Outcome Variable, Mean change From Baseline to Month 6 in Perimetric Mean Deviation (PMD) in the Study Eye. Perimetric mean deviation is a measure of global visual field loss (mean deviation from age-corrected normal values), with a range of 2 to -32 dB; larger negative values indicate greater vision loss. (NCT01003639)
Timeframe: base line and 6 months

InterventiondB (Mean)
Acetazolamide1.43
Sugar Pill0.71

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Colonic Geometric Center at 4 Hours

The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit. A GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool. (NCT01055704)
Timeframe: 4 hours

InterventionUnits on a scale (Mean)
Methylnaltrexone 0.30 mg/kg0.236
Codeine 30 mg0
Methylnaltrexone 0.30 mg/kg + Codeine 30 mg0.379
Placebo0.347

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Colonic Geometric Center at 48 Hours

The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit. A GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool. (NCT01055704)
Timeframe: 48 hours

InterventionUnits on a scale (Mean)
Methylnaltrexone 0.30 mg/kg3.9
Codeine 30 mg3.3
Methylnaltrexone 0.30 mg/kg + Codeine 30 mg2.8
Placebo4.1

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Stool Consistency as Reported From the Bristol Stool Scale

"Bristol Stool Scale a medical aid designed to classify the form of human feces into seven categories or types. Types 1 and 2 indicate constipation, with 3 and 4 being the ideal stools especially the latter, as they are the easiest to defecate, and 5-7 tending towards diarrhea." (NCT01055704)
Timeframe: Daily

InterventionUnits on a scale (Mean)
Methylnaltrexone 0.30 mg/kg3.4
Codeine 30 mg3.1
Methylnaltrexone 0.30 mg/kg + Codeine 30 mg3.3
Placebo3.7

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Stool Frequency

Stool frequency was self reported in a daily bowel pattern diary for 13 days. (NCT01055704)
Timeframe: daily

InterventionStools (Mean)
Methylnaltrexone 0.30 mg/kg1.1
Codeine 30 mg0.63
Methylnaltrexone 0.30 mg/kg + Codeine 30 mg0.7
Placebo1.5

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Colonic Filling at 6 Hours

Percent of solids reaching the colon at 6 hours (NCT01055704)
Timeframe: 6 hours

InterventionPercentage (Mean)
Methylnaltrexone 0.30 mg/kg21.9
Codeine 30 mg23.7
Methylnaltrexone 0.30 mg/kg + Codeine 30 mg28.0
Placebo34.5

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T1/2 of Ascending Colon Emptying

(NCT01055704)
Timeframe: 24 hours

Interventionhours (Mean)
Methylnaltrexone 0.30 mg/kg17.1
Codeine 30 mg24.0
Methylnaltrexone 0.30 mg/kg + Codeine 30 mg23.6
Placebo14.1

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T1/2 of Gastric Emptying of Solid

(NCT01055704)
Timeframe: 4 hours

InterventionMinutes (Mean)
Methylnaltrexone 0.30 mg/kg102.7
Codeine 30 mg104.0
Methylnaltrexone 0.30 mg/kg + Codeine 30 mg126.8
Placebo101.1

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Colonic Geometric Center at 24 Hours

The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit. A GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool. (NCT01055704)
Timeframe: 24 hours

InterventionUnits on a scale (Mean)
Methylnaltrexone 0.30 mg/kg2.3
Codeine 30 mg1.8
Methylnaltrexone 0.30 mg/kg + Codeine 30 mg1.9
Placebo2.3

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Subjects' Overall Assessment of the Study Medication Assessed at 12 Hours or Just Before Administration of Rescue Medication

"Subject's Overall Assessment measured by subject ticking the appropriate box in response to the question 'How effective do you think the study medication is as a treatment for pain?'~Subject's Overall Assessment rated on a five-point ordinal scale: 1 = Poor, 2 = Fair, 3 = Good, 4 = Very good, and 5 = Excellent." (NCT01229449)
Timeframe: At 12 hours

,,,,
InterventionParticipants (Count of Participants)
1 Poor2 Fair3 Good4 Very good5 Excellent
Ibuprofen 200mg + Paracetamol 500mg (Lower Dose)1516437223
Ibuprofen 400mg + Paracetamol 1000mg (Higher Dose)912326939
Nurofen Plus®1522406426
Panadeine® Extra121941347
Placebo436231

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Change From Baseline in Area Under the Curve (AUC) of Pain Intensity and Relief Scores (SPRID)

"SPRID 0-12h: Sum of pain intensity difference (PID) and the pain relief (PR) score over the twelve-hour follow-up period. Score range: 0mm = No pain and 100mm = Worst pain. This was calculated as the area under the curve (AUC) using the method of linear trapezoids assuming that the baseline assessment took place at time zero.~Pain intensity (PI) was measured by pain assessment questionnaire, where subject tick the appropriate box in a 4-point ordinal scale ranging from 0 = No pain, 1 = Mild pain, 2 = Moderate pain, and 3 = Severe pain, in response to the question 'What is your pain level at this time?'~Total Pain Relief (TOTPAR) was measured using pain assessment diary, where subject tick the appropriate box on a 5-point Ordinal Rating Scale: 0 = None, 1 = A Little, 2 = Some, 3 = A Lot, and 4 = Complete, in response to the question 'How much relief have you had from your starting pain?'" (NCT01229449)
Timeframe: 0 (baseline), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose

Interventionunits on a scale*hour (Mean)
Ibuprofen 200mg + Paracetamol 500mg (Lower Dose)2.68
Ibuprofen 400mg + Paracetamol 1000mg (Higher Dose)3.30
Nurofen Plus®2.62
Panadeine® Extra1.93
Placebo0.54

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Change From Baseline in Peak Pain Intensity Difference (Peak PID - Ordinal)

"Pain intensity (PI) was measured by pain assessment questionnaire where subject tick the appropriate box in response to the question 'What is your pain level at this time?'~PI measured using a 4-point ordinal scale: 0 = No pain, 1 = Mild pain, 2 = Moderate pain, and 3 = Severe pain." (NCT01229449)
Timeframe: 0 (baseline), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose

Interventionunits on a scale (Mean)
Ibuprofen 200mg + Paracetamol 500mg (Lower Dose)1.78
Ibuprofen 400mg + Paracetamol 1000mg (Higher Dose)1.93
Nurofen Plus®1.74
Panadeine® Extra1.63
Placebo0.60

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Change From Baseline in Peak Pain Relief (PR)

"Total pain relief (TOTPAR) was measured using pain assessment diary where subject tick the appropriate box in response to the question 'How much relief have you had from your starting pain?'~Pain Relief (PR) was rated on a 5-point Ordinal Rating Scale: 0 = None, 1 = A Little, 2 = Some, 3 = A Lot, and 4 = Complete." (NCT01229449)
Timeframe: 0 (baseline), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post-dose

Interventionunits on a scale (Mean)
Ibuprofen 200mg + Paracetamol 500mg (Lower Dose)3.06
Ibuprofen 400mg + Paracetamol 1000mg (Higher Dose)3.25
Nurofen Plus®2.98
Panadeine® Extra2.88
Placebo0.96

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Change From Baseline in AUC (0-8h) of SPRID

"SPRID 0-8h: Sum of pain intensity difference (PID) and the pain relief (PR) score over the twelve-hour follow-up period. Score range: 0 mm = No pain and 100 mm = Worst pain. This was calculated as the area under the curve (AUC) using the method of linear trapezoids assuming that the baseline assessment took place at time zero.~Pain intensity (PI) was measured by pain assessment questionnaire, where subject tick the appropriate box in a 4-point ordinal scale ranging from 0 = No pain, 1 = Mild pain, 2 = Moderate pain, and 3 = Severe pain, in response to the question 'What is your pain level at this time?'~Total Pain Relief (TOTPAR) was measured using pain assessment diary, where subject tick the appropriate box on a 5-point Ordinal Rating Scale: 0 = None, 1 = A Little, 2 = Some, 3 = A Lot, and 4 = Complete, in response to the question 'How much relief have you had from your starting pain?'" (NCT01229449)
Timeframe: 0 (baseline), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, and 8 hours post-dose

,,,,
Interventionunits on a scale*hour (Mean)
0-4h0-6h0-8h
Ibuprofen 200mg + Paracetamol 500mg (Lower Dose)3.653.663.39
Ibuprofen 400mg + Paracetamol 1000mg (Higher Dose)3.954.063.91
Nurofen Plus®3.443.453.22
Panadeine® Extra3.192.862.48
Placebo0.610.600.57

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Change From Baseline in AUC of Individual Reading Pain Intensity and Relief Scores (SPRID)

"SPRID 0-12h: Sum of pain intensity difference (PID) and the pain relief (PR) score over the twelve-hour follow-up period. Score range: 0mm = No pain and 100mm = Worst pain. This was calculated as the area under the curve (AUC) using the method of linear trapezoids assuming that the baseline assessment took place at time zero.~Pain intensity (PI) was measured by pain assessment questionnaire, where subject tick the appropriate box in a 4-point ordinal scale ranging from 0 = No pain, 1 = Mild pain, 2 = Moderate pain, and 3 = Severe pain, in response to the question 'What is your pain level at this time?'~Total Pain Relief (TOTPAR) was measured using pain assessment diary, where subject tick the appropriate box on a 5-point Ordinal Rating Scale: 0 = None, 1 = A Little, 2 = Some, 3 = A Lot, and 4 = Complete, in response to the question 'How much relief have you had from your starting pain?'" (NCT01229449)
Timeframe: 15, 30, 45, 60, 90 minutes and 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours

,,,,
Interventionunits on a scale (Mean)
15 minutes30 minutes45 minutes60 minutes90 minutes2 hours3 hours4 hours5 hours6 hours7 hours8 hours9 hours10 hours11 hours12 hours
Ibuprofen 200mg + Paracetamol 500mg (Lower Dose)1.122.493.203.714.124.284.184.083.773.062.562.091.571.210.900.69
Ibuprofen 400mg + Paracetamol 1000mg (Higher Dose)1.292.793.524.044.444.514.534.464.363.983.512.792.532.041.631.34
Nurofen Plus®0.782.082.923.493.924.174.023.783.522.982.542.081.681.301.120.96
Panadeine® Extra1.012.623.393.813.963.913.312.792.231.701.311.020.910.810.760.74
Placebo0.290.580.650.710.600.671.660.640.600.530.450.400.470.490.490.49

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Change From Baseline in AUC of Pain Relief Scores (TOTPAR)

"Total pain relief (TOTPAR) was measured using pain assessment diary where subject tick the appropriate box in response to the question 'How much relief have you had from your starting pain?'~Pain Relief (PR) was rated on a 5-point Ordinal Rating Scale: 0 = None, 1 = A Little, 2 = Some, 3 = A Lot, and 4 = Complete." (NCT01229449)
Timeframe: 0-4, 0-6, 0-8 and 0-12 hours

,,,,
Interventionunits on a scale*hour (Mean)
0-4h0-6h0-8h0-12h
Ibuprofen 200mg + Paracetamol 500mg (Lower Dose)2.332.342.181.73
Ibuprofen 400mg + Paracetamol 1000mg (Higher Dose)2.482.562.482.12
Nurofen Plus®2.202.222.081.70
Panadeine® Extra2.051.851.611.27
Placebo0.420.410.380.34

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Individual Pain Intensity Differences (Ordinal)

"Pain intensity (PI) was measured by pain assessment questionnaire where subject tick the appropriate box in response to the question 'What is your pain level at this time?'~PI measured using a 4-point ordinal scale: 0 = No pain, 1 = Mild pain, 2 = Moderate pain, and 3 = Severe pain." (NCT01229449)
Timeframe: 15, 30, 45, 60, 90 minutes and 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours

,,,,
Interventionunits on a scale (Mean)
15 minutes30 minutes45 minutes60 minutes90 minutes2 hours3 hours4 hours5 hours6 hours7 hours8 hours9 hours10 hours11 hours12 hours
Ibuprofen 200mg + Paracetamol 500mg (Lower Dose)0.400.941.141.311.491.541.541.491.351.070.890.710.530.400.270.21
Ibuprofen 400mg + Paracetamol 1000mg (Higher Dose)0.461.031.271.481.611.691.701.681.601.441.220.960.860.670.520.42
Nurofen Plus®0.230.731.041.241.401.521.461.361.241.040.880.720.550.430.360.30
Panadeine® Extra0.310.951.191.351.421.411.190.960.790.580.440.330.290.270.240.25
Placebo0.090.150.160.220.110.240.220.240.220.200.180.160.200.200.200.20

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Individual Pain Intensity Differences Visual Analogue Scale (VAS)

Pain Intensity (PI) VAS was measured using a horizontal 100-mm VAS ranging 0 mm = 'No Pain' as the left anchor and 100 mm = 'Worst Pain' as the right anchor, labelled by the subject marking the VAS line in the pain assessment questionnaire in response to the instruction 'Please indicate with a line on the scale below your pain at this time.' (NCT01229449)
Timeframe: 15, 30, 45, 60, 90 minutes and 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 hours

,,,,
Interventionunits on a scale (Mean)
15 minutes30 minutes45 minutes60 minutes90 minutes2 hours3 hours4 hours5 hours6 hours7 hours8 hours9 hours10 hours11 hours12 hours
Ibuprofen 200mg + Paracetamol 500mg (Lower Dose)9.022.832.540.348.350.651.050.245.436.630.925.017.714.19.48.0
Ibuprofen 400mg + Paracetamol 1000mg (Higher Dose)10.526.237.546.352.554.955.955.552.847.941.033.829.623.718.715.1
Nurofen Plus®4.517.728.336.643.747.348.045.642.535.629.724.418.414.912.811.0
Panadeine® Extra8.723.934.341.544.645.238.932.925.918.415.411.710.89.79.89.3
Placebo0.42.20.91.80.95.06.17.27.26.55.85.15.66.26.26.4

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Change From Baseline in AUC for Pain Intensity Difference Scores (SPID)

Sum of Pain Intensity Difference (SPID) was calculated as the area under the curve (AUC) using the method of linear trapezoids assuming that the baseline assessment took place at time zero. Score range: 0mm = No pain and 100mm = Worst pain. Pain intensity (PI) was measured by pain assessment questionnaire, where subject tick the appropriate box in a 4-point ordinal scale ranging from 0 = No pain, 1 = Mild pain, 2 = Moderate pain, and 3 = Severe pain, in response to the question 'What is your pain level at this time?' (NCT01229449)
Timeframe: 0-4, 0-6, 0-8 and 0-12 hours

,,,,
Interventionunits on a scale*hour (Mean)
0-4h0-6h0-8h0-12h
Ibuprofen 200mg + Paracetamol 500mg (Lower Dose)1.321.321.210.94
Ibuprofen 400mg + Paracetamol 1000mg (Higher Dose)1.461.501.431.18
Nurofen Plus®1.231.231.140.91
Panadeine® Extra1.131.010.870.67
Placebo0.180.190.190.19

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Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period.

Parent-reported side effects entered in 10-day diary. (NCT01267136)
Timeframe: Side effects will be observed and recorded daily by caregivers for a total of 10 days in the take-home diary.

,
Interventionparticipants (Number)
NauseaVomitingFeverItchingRashSweatingDizzinessHeadacheConstipationOversedationTonsil bleed
Capital® With Codeine Suspension202111519151221143
Tramadol Suspension201810121717172180

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Efficacy of Two Different Liquid Pain Medications: Tramadol vs. Codeine/Acetaminophen During the Post-tonsillectomy Recovery Period.

Average number of post-operative days with pain score >4/10. Pain score assessments were administered once daily by parents using either the Numeric Rating Scale (NRS-11) (with anchors 0=no pain and 10=highest pain imaginable) for children ages 8-15 (von Baeyer et al., 2009) or the Faces Pain Scale-Revised (FPS-R) (with anchors 0=no pain and 10=highest pain imaginable) for children ages 4-10 (Hicks et al., 2001). (NCT01267136)
Timeframe: Efficacy was assessed daily during the 10-day postoperative recovery period.

Interventiondays (Median)
Capital® With Codeine Suspension1.5
Tramadol Suspension1

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Overall Satisfaction With the Pain Medicine

Overall satisfaction with the oral opioid pain medication at 24 hours after discharge using a Likert scale. Patients will be asked to describe their overall experience as being very satisfied, satisfied, unsatisfied or very unsatisfied with the study medication. (NCT01402375)
Timeframe: 24 hrs

,,,,,
InterventionParticipants (Count of Participants)
Number of participants satisfied with analgesicparticipants would want the same analgesic again
Codeine (First Trial)6666
Codeine (for Second Trial)9185
Hydrocodone (First Trial)7259
Hydrocodone (Third Trial)9790
Oxycodone (for Second Trial)9991
Oxycodone (Third Trial)9386

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Difference in Pain Intensity Score Before and After Last Dose.

"Pain intensity is measured on the numerical rating scale (NRS) from 0 (no pain) to 10 (worst pain imaginable). The difference in pain score is calculated by subtracting the average score 2 hours after pain medication is taken from the average pain score immediately before the pain medication is taken." (NCT01402375)
Timeframe: 2 hrs

,,,,,
Interventionunits on a scale (Mean)
before most recent dose2 hours after most recent dosechange in NRS before to after most recent dose
Codeine (First Trial)7.64.13.5
Codeine (for Second Trial)7.93.64.2
Hydrocodone (First Trial)7.63.63.9
Hydrocodone (Third Trial)7.63.64.0
Oxycodone (for Second Trial)7.93.44.5
Oxycodone (Third Trial)7.83.34.4

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Time to Follow up

Median time to contact patients for data collection, measured from discharge to time contacted (NCT01402375)
Timeframe: up to 48 hours

Interventionhours (Median)
Hydrocodone (First Trial)27
Codeine (First Trial)25
Oxycodone (for Second Trial)26
Codeine (for Second Trial)28
Oxycodone (Third Trial)27
Hydrocodone (Third Trial)28

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50% or Greater Decrease in Numerical Rating Scale (NRS) Pain Score

(NCT01402375)
Timeframe: 2 hours

InterventionParticipants (Count of Participants)
Hydrocodone (First Trial)50
Codeine (First Trial)45
Oxycodone (for Second Trial)73
Codeine (for Second Trial)64
Oxycodone (Third Trial)68
Hydrocodone (Third Trial)66

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Number of Participants With Adequate Relief of Headache as a Measure of Efficacy

Number of participants with reduction in pain scores six hours post administration by at least 2 on the pain score scale. (NCT02295280)
Timeframe: Primary outcome was six hours post administration

InterventionParticipants (Count of Participants)
Metoclopramide IV & Diphenhydramine IV34
Codeine32

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Between Group Difference in Change in Numerical Rating Scale (NRS) Pain Scores

Change in numerical rating scale (NRS) pre and 1-hour post receiving study medication while in the ED. The NRS is a validated 11-point numerical scale that ranges from 0 (no pain) to 10 (worst pain possible) (NCT02455518)
Timeframe: 1 hour

Interventionunits on a scale (Number)
Oxycodone/Acetaminophen3.1
Hydrocodone/Acetaminophen2.4
Codeine/Acetaminophen2.7
Ibuprofen/Acetaminophen2.9

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Between Group Difference in Change in Numerical Rating Scale (NRS) Pain Scores

Change in numerical rating scale (NRS) pre and 2 hours post receiving study medication while in the ED. The NRS is a validated 11-point numerical scale that ranges from 0 (no pain) to 10 (worst pain possible) (NCT02455518)
Timeframe: 2 hours

Interventionunits on a scale (Number)
Oxycodone/Acetaminophen4.4
Hydrocodone/Acetaminophen3.5
Codeine/Acetaminophen3.9
Ibuprofen/Acetaminophen4.3

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Number of Pills Used

(NCT02647788)
Timeframe: From the time of surgery to first clinic visit (post-op day 6 to 8)

InterventionPills (Mean)
Acetaminophen/Ibuprofen13.72
Acetaminophen/Codeine14.14

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Quality of Recovery-9 (QoR-9).

To establish whether the opioid versus non-opioid post-operative pain regimen influences patient satisfaction through Quality of Recovery (QoR) scores in ambulatory hand surgery. This 9 question survey has a maximum score (best outcome) of 18 and minimum (worst outcome) of 3. The survey was administered over the phone on post-operative day 2. (NCT02647788)
Timeframe: Postoperative Day 2

InterventionScores on a scale (Mean)
Acetaminophen/Ibuprofen16.91
Acetaminophen/Codeine16.65

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Assessing Change in Pain Using the Visual Analogue Scale (VAS) Pain Score

To establish, through a randomized control trial, whether post-operative Acetaminophen and Ibuprofen (non-opioid regimen) would provide equivalent post-operative analgesia to ambulatory hand surgery patients compared to Acetaminophen and Codeine (opioid regimen). The pain VAS is a continuous scale where 0=no pain and 10=worst pain imaginable. (NCT02647788)
Timeframe: Subjects reported pain 3 times a day each day after hand surgery (at dinner time, before going to sleep and in the middle of the night), until post-op appointment (between 4 and 8 days after surgery). The numbers reported are the average daily pain scores

,
Interventionscore on a scale (Mean)
VAS Pain Day 1VAS Pain Day 2VAS Pain Day 3VAS Pain Day 4VAS Pain Day 5VAS Pain Day 6VAS Pain Day 7
Acetaminophen/Codeine3.512.402.261.931.481.351.01
Acetaminophen/Ibuprofen2.902.361.691.471.231.291.17

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Mean Change From Baseline in NRS Pain Score at Time of Presentation for D&E Procedure (Day Following Dilator Insertion)

Pain score based on numeric rating scale (NRS [0 lowest value to 10 highest value, in which 0 is the lowest amount of pain and 10 is the highest amount of pain]); Baseline obtained prior to study drug ingestion/dilator insertion. NRS pain score obtained in person upon presentation for D&E procedure. (NCT03080493)
Timeframe: Time of presentation for D&E (day after dilator insertion)

InterventionNumeric rating scale pain score change (Median)
Gabapentin0.5
Placebo Oral Capsule1

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Mean Change From Baseline in NRS Pain Score at 8 Hours After Dilator Insertion

Pain score based on numeric rating scale (NRS [0 lowest value to 10 highest value, in which 0 is the lowest amount of pain and 10 is the highest amount of pain]); Baseline obtained prior to study drug ingestion/dilator insertion. NRS pain score obtained via text message. (NCT03080493)
Timeframe: 8 hours after insertion of last osmotic dilator

InterventionNumeric rating scale pain score change (Median)
Gabapentin2
Placebo Oral Capsule2.5

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Mean Change From Baseline in NRS Pain Score at 5 Minutes After Last Dilator Insertion

Pain score based on numeric rating scale (NRS [0 lowest value to 10 highest value, in which 0 is the lowest amount of pain and 10 is the highest amount of pain]); Baseline obtained prior to study drug ingestion/dilator insertion. NRS pain score obtained in person before subject leaves clinic appointment. (NCT03080493)
Timeframe: 5 minutes after insertion of last osmotic dilator

InterventionNumeric rating scale pain score change (Median)
Gabapentin1
Placebo Oral Capsule2

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Mean Change From Baseline in NRS Pain Score at 4 Hours After Dilator Insertion

Pain score based on numeric rating scale (NRS [0 lowest value to 10 highest value, in which 0 is the lowest amount of pain and 10 is the highest amount of pain]); Baseline obtained prior to study drug ingestion/dilator insertion. NRS pain score obtained via text message. (NCT03080493)
Timeframe: 4 hours after insertion of last osmotic dilator

InterventionNumeric rating scale pain score change (Mean)
Gabapentin3
Placebo Oral Capsule3.5

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Mean Change From Baseline in NRS Pain Score at 2 Hours After Dilator Insertion

Pain score based on numeric rating scale (NRS [0 lowest value to 10 highest value, in which 0 is the lowest amount of pain and 10 is the highest amount of pain]); Baseline obtained prior to study drug ingestion/dilator insertion. NRS pain score obtained via text message. (NCT03080493)
Timeframe: 2 hours after insertion of last osmotic dilator

InterventionNumeric rating scale pain score change (Median)
Gabapentin3.5
Placebo Oral Capsule4

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Number of Participants Using Narcotic Pain Medication (Acetaminophen/Codeine)

Subject account of how many used acetaminophen/codeine (standard medications given for supplement NSAID as needed after dilator insertion) (NCT03080493)
Timeframe: Collected between each subject contact (2 hours, 4 hours, 8 hours after dilator insertion and at time of presentation for D&E procedure)

InterventionParticipants (Count of Participants)
Gabapentin35
Placebo Oral Capsule40

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Change in Pain From Before Medication Administered (Baseline) to One-hour Post-baseline

Pain intensity measured by 11-point Numerical Rating Scale (NRS) of Pain 0 = no pain 10 = worse possible pain. Change calculated as NRS before medication administered (denoted as baseline) minus NRS 1-hour post-baseline. Higher scores mean more change which is the better outcome. (NCT03173456)
Timeframe: Prior to Ingestion of study medication to one hour after ingestion of the study medication

InterventionUnits on a scale (Mean)
400 Ibuprofen/APAP3.0
800 Ibuprofen/APAP3.0
Codeine/APAP3.4
Hydrocodone/APAP3.1
Oxycodone/APAP3.3

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Percentage of Patients Who Would Choose to Take the Study Medication Again if They Returned to the ED With Similar Pain

Number of patients who would choose to take study medication again divided by number of patients x 100. Question asked at end of two-hour time period (NCT03173456)
Timeframe: End of two-hour time period

InterventionParticipants (Count of Participants)
400 Ibuprofen/APAP78
800 Ibuprofen/APAP83
Codeine/APAP75
Hydrocodone/APAP89
Oxycodone/APAP81

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Percentage of Patients Who Received Rescue Medication

Number of patients who received additional analgesics divided by total number of patients x 100 (NCT03173456)
Timeframe: Entire two-hour time period

InterventionParticipants (Count of Participants)
400 Ibuprofen/APAP29
800 Ibuprofen/APAP28
Codeine/APAP26
Hydrocodone/APAP27
Oxycodone/APAP28

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Percentage of Patients Who Experience Side Effects Within One Hour of Ingestion of Study Medication

Number of patients who experience side effects within one hour ofr ingestion of study medication divided by total number of patients x 100 (NCT03173456)
Timeframe: From time of ingestion of study medication to one hour later

InterventionParticipants (Count of Participants)
400 Ibuprofen/APAP26
800 Ibuprofen/APAP37
Codeine/APAP33
Hydrocodone/APAP34
Oxycodone/APAP37

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Percentage of Patients Who Experience Side Effects in Two Hours After Ingestion of Study Medication

Number of patients who experience side effects in two hours after ingestion of study medication divided by total number of patients x 100 (NCT03173456)
Timeframe: From time of ingestion of study medication to two hours later

InterventionParticipants (Count of Participants)
400 Ibuprofen/APAP31
800 Ibuprofen/APAP44
Codeine/APAP40
Hydrocodone/APAP51
Oxycodone/APAP49

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Change in Pain From Before Medication Administered (Baseline) to Two Hour Post-baseline

Pain intensity measured by 11-point Numerical Rating Scale (NRS) of Pain 0 = no pain 10=worst possible pain. Change is calculated as Numerical Rating Scale before medication is administered (denoted as baseline) minus NRS 2- hours past baseline. Higher numbers indicate better outcomes. (NCT03173456)
Timeframe: Prior to ingestion of study medication to 2 hours after ingestion of the study medication

Interventionunits on a scale (Mean)
400 Ibuprofen/APAP4.3
800 Ibuprofen/APAP4.6
Codeine/APAP4.4
Hydrocodone/APAP4.5
Oxycodone/APAP4.7

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Pain Evaluation

Evaluation of changes in Visual Analog Scale measurements by groups (0 = no pain; 10 = unbearable pain) (NCT04066426)
Timeframe: Pre-treatment (baseline)

Interventionscore on a scale (Mean)
Naproxen Sodium+Codeine Phosphate6.38
Naproxen Sodium+Dexamethasone6.93
Naproxen Sodium5.76
Paracetamol5.49

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Pain Evaluation

Evaluation of changes in Visual Analog Scale measurements by groups (0 = no pain; 10 = unbearable pain). (NCT04066426)
Timeframe: At the first month

Interventionscore on a scale (Mean)
Naproxen Sodium+Codeine Phosphate2.93
Naproxen Sodium+Dexamethasone5.28
Naproxen Sodium3.69
Paracetamol4.38

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Pain Evaluation

Evaluation of changes in Visual Analog Scale measurements by groups (0 = no pain; 10 = unbearable pain). (NCT04066426)
Timeframe: At the first week

Interventionscore on a scale (Mean)
Naproxen Sodium+Codeine Phosphate4.68
Naproxen Sodium+Dexamethasone5.93
Naproxen Sodium4.95
Paracetamol4.60

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Pain Evaluation

Evaluation of changes in Visual Analog Scale measurements by groups (0 = no pain; 10 = unbearable pain). (NCT04066426)
Timeframe: At the second week

Interventionscore on a scale (Mean)
Naproxen Sodium+Codeine Phosphate3.58
Naproxen Sodium+Dexamethasone5.28
Naproxen Sodium4.33
Paracetamol4.34

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Post-operative Uncorrected Visual Acuity Right and Left Eye

Right and left eye uncorrected visual acuity at post-operative month 6. (NCT04399122)
Timeframe: Post-operative month 6.

,
InterventionlogMAR (Mean)
Right Eye logMARLeft Eye logMAR
Acetaminophen With Codeine-0.07-0.06
Acetaminophen With Oxycodone-0.05-0.06

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Post-operative Average Pain Score

The PRK Post-Operative Pain Survey consisted of a scale of 0 - 10 with a score of 0 equal to no pain, a score of 1 - 3 equal to mild pain, a score of 4 - 6 equal to moderate pain and a score of 7 - 10 equal to severe pain (NCT04399122)
Timeframe: 2 days post surgery

Interventionunits on a scale (Mean)
Acetaminophen With Codeine2.82
Acetaminophen With Oxycodone3.58

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