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Effect of psychotropic medication on the in vitro metabolism of buprenorphine in human cDNA-expressed cytochrome P450 enzymes

  • Pharmacokinetics and Disposition
  • Published:
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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, IC50 values without preincubation were higher than those after 30-min preincubation, with zolpidem 113.1 μM and midazolam 20.25 μM. Following a 30-min preincubation period in the absence of the probe substrate BUP, the apparent IC50 values for zolpidem and midazolam were 20.17 μM and 3.5 μM.

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.

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Acknowledgements

The authors would like to thank Ms. Hönekopp and her team from a local substitution center in Mannheim, Germany, giving assistance to select prescribed and illicitly used drugs of potential interaction, and Prof. Mikus, Department of Internal Medicine VI, University of Heidelberg, Germany, for helpful discussion.

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Authors and Affiliations

  1. Institute of Legal Medicine and Traffic Medicine, Ruprecht-Karls University, Voßstr. 2, 69115, Heidelberg, Germany

    Stephanie Bomsien, Rolf Aderjan, Rainer Mattern & Gisela Skopp

Authors
  1. Stephanie Bomsien
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  2. Rolf Aderjan
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  3. Rainer Mattern
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  4. Gisela Skopp
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Correspondence to Stephanie Bomsien.

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Bomsien, S., Aderjan, R., Mattern, R. et al. Effect of psychotropic medication on the in vitro metabolism of buprenorphine in human cDNA-expressed cytochrome P450 enzymes. Eur J Clin Pharmacol 62, 639–643 (2006). https://doi.org/10.1007/s00228-006-0147-6

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  • DOI: https://doi.org/10.1007/s00228-006-0147-6

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