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Effect of omeprazole on the pharmacokinetics of moclobemide according to the genetic polymorphism of CYP2C19
Author(s) -
Yu KyungSang,
Yim DongSeok,
Cho JooYoun,
Park Soon Seong,
Park Ji Young,
Lee KyungHoon,
Jang InJin,
Yi SoYoung,
Bae KyunSeop,
Shin SangGoo
Publication year - 2001
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1067/mcp.2001.114231
Subject(s) - moclobemide , cyp2c19 , omeprazole , pharmacokinetics , pharmacology , placebo , lansoprazole , crossover study , medicine , chemistry , antidepressant , cytochrome p450 , metabolism , alternative medicine , pathology , hippocampus
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. Clinical Pharmacology & Therapeutics (2001) 69 , 266–273; doi: 10.1067/mcp.2001.114231