Effect of Psychotropic Medication on the in Vitro Metabolism of Buprenorphine in Human CDNA-expressed Cytochrome P450 Enzymes

Overview

Journal Eur J Clin Pharmacol

Specialty Pharmacology

Date 2006 Jun 28

PMID 16802166

Citations 2

Authors

Stephanie Bomsien

Rolf Aderjan

Rainer Mattern

Gisela Skopp

Affiliations

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Abstract

Objective: The aim of the present study was to estimate the drug interaction potential of psychtropic medication on buprenorphine (BUP) N-dealkylation using cDNA-expressed cytochrome P450 (CYP) enzymes.

Methods: BUP was incubated with psychotropic drugs and cDNA-expressed CYP 3A4 and CYP 2C8 enzymes. Seven substances were screened for their inhibition potency. To check for a mechanism-based component in inhibition, all substances were tested with and without preincubation, respectively. Norbuprenorphine (NBUP) concentrations were determined by liquid chromatography/tandem mass spectrometry, following liquid/liquid extraction.

Results: Midazolam and zolpidem demonstrated greatest inhibition in screening experiments. As expected, IC(50) values without preincubation were higher than those after 30-min preincubation, with zolpidem 113.1 microM and midazolam 20.25 microM. Following a 30-min preincubation period in the absence of the probe substrate BUP, the apparent IC(50) values for zolpidem and midazolam were 20.17 microM and 3.5 microM.

Conclusion: Both midazolam and zolpidem showed a distinct inhibitory potency towards NBUP formation by CYP 3A4, implicating a decreased conversion of BUP. When preincubated, the inhibitory potency was increased, which strongly suggests a metabolically activated component in inhibition.

Citing Articles

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