Effect of omeprazole on the pharmacokinetics of moclobemide according to the genetic polymorphism of CYP2C19 View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2001-04

AUTHORS

Kyung‐Sang Yu, Dong‐Seok Yim, Joo‐Youn Cho, Soon Seong Park, Ji Young Park, Kyung‐Hoon Lee, In‐Jin Jang, So‐Young Yi, Kyun‐Seop Bae, Sang‐Goo Shin

ABSTRACT

BACKGROUND: Moclobemide, an antidepressant with selective monoamine oxidase-A inhibitory action, is known to be metabolized by CYP2C19 and is also reported to be an inhibitor of CYP2C19, CYP2D6, and CYP1A2. To confirm the involvement of CYP2C19, we performed a pharmacokinetic interaction study. METHODS: The effect of omeprazole on the pharmacokinetics of moclobemide was studied in 16 healthy volunteers. The volunteer group comprised 8 extensive metabolizers and 8 poor metabolizers of CYP2C19, which was confirmed by genotyping. Subjects were randomly allocated into two sequence groups, and a single-blind, placebo-controlled, two-period crossover study was performed. In study I, a placebo was orally administered for 7 days. On the eighth morning, 300 mg of moclobemide and 40 mg of placebo were coadministered with 200 mL of water, and a pharmacokinetic study was performed. During study II, 40 mg of omeprazole was given each morning instead of placebo, and pharmacokinetic studies were performed on the first and eighth day with 300 mg of moclobemide coadministration. RESULTS: The inhibition of moclobemide metabolism was significant in extensive metabolizers even after a single dose of omeprazole. After daily administration of omeprazole for 1 week, the pharmacokinetic parameters of moclobemide and its metabolites in extensive metabolizers changed to values similar to those in poor metabolizers. In poor metabolizers, no remarkable changes in the pharmacokinetic parameters were observed. CONCLUSION: Our results show that CYP2C19 is an important enzyme in the elimination of moclobemide and that it is extensively inhibited by omeprazole in extensive metabolizers, but not in poor metabolizers. More... »

PAGES

266-273

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1067/mcp.2001.114231

    DOI

    http://dx.doi.org/10.1067/mcp.2001.114231

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1019407656

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/11309556


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