ArticleEuropean journal of clinical pharmacology2005
Effect of benzodiazepines on the metabolism of buprenorphine in human liver microsomes.
Article in European journal of clinical pharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed, 29 citations in OpenAlex.
- Clinical characteristics of central European and North American samples of pregnant women screened for opioid agonist treatment.European addiction research · 2010Trial
- Prediction of Drug-Drug Interactions Between Opioids and Overdosed Benzodiazepines Using Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation.Drugs in R&D · 2019Article
- New developments in the management of opioid dependence: focus on sublingual buprenorphine-naloxone.Substance abuse and rehabilitation · 2015Review
- Polydrug abuse: a review of opioid and benzodiazepine combination use.Drug and alcohol dependence · 2012Review
- Effect of rifampin and nelfinavir on the metabolism of methadone and buprenorphine in primary cultures of human hepatocytes.Drug metabolism and disposition: the biological fate of chemicals · 2009Article
- Effect of psychotropic medication on the in vitro metabolism of buprenorphine in human cDNA-expressed cytochrome P450 enzymes.European journal of clinical pharmacology · 2006Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
objectiveTo determine whether enzyme inhibition explains the clinical adverse interaction of benzodiazepines and buprenorphine.
methodsBuprenorphine was incubated in the presence of benzodiazepines (or metabolites) with human liver microsomes (HLMs). A number of benzodiazepines were screened at therapeutic concentrations after 0-min and 15-min preincubation times. For tentative metabolically activated inhibitors, the kinetics of inhibition was studied in a secondary incubation system. Buprenorphine and norbuprenorphine were quantified by means of liquid chromatography-mass spectrometry.
resultsBuprenorphine elimination and norbuprenorphine formation were at most reduced by 26% (i.e., weak or negligible inhibition). Evidence of metabolically activated inhibition suggested the need for further studies on the inhibitory kinetics. Midazolam caused time- and concentration-dependent inhibition of norbuprenorphine formation with pseudo-first-order kinetics, and K(I) and k(inact) values of 10.5 microM and 0.045 min(-1), respectively. Mixed-type inhibition of buprenorphine elimination (K(i) = 30-35 microM) and a noncompetitive inhibition of norbuprenorphine formation were also observed. For clonazepam (up to 10 microM), 3-hydroxy-7-acetamidoclonazepam (up to 10 microM), and alpha-hydroxy-triazolam (up to 1.0 microM), no time- or concentration-dependent inhibition of buprenorphine metabolism was found.
conclusionA single benzodiazepine, midazolam, is a moderate mechanism-based inactivator of buprenorphine N-dealkylation. It is anticipated that repeated exposures to midazolam might alter the in vivo metabolism of buprenorphine.
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