Possible inhibitory effect of diazepam on the metabolism of zotepine,an antipsychotic drug |
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Authors: | T. Kondo Osamu Tanaka Koichi Otani Kazuo Mihara Noboru Tokinaga Sunao Kaneko K. Chiba Takashi Ishizaki |
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Affiliation: | (1) Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki 036, Japan, JP;(2) Department of Clinical Pharmacology, Research Institute, International Medical Center of Japan, Tokyo 162, Japan, JP |
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Abstract: | Effects of smoking and cytochrome P450 2C19 (CYP2C19) status on the single dose kinetics of zotepine and pharmacokinetic interaction between zotepine and diazepam were investigated. In 14 healthy volunteers, the pharmacokinetics of zotepine after a single oral 25 mg dose were compared between eight smokers and six non-smokers, or between seven extensive metabolizers (EMs) and seven poor metabolizers (PMs) of S-mephenytoin. There was no significant difference in any pharmacokinetic parameters between smokers and non-smokers, or between the EM and PM groups. In 17 patients treated with zotepine 80–340 mg/day, intra-individual changes in plasma concentrations of zotepine caused by coadministration of diazepam 10 mg/day for 2 weeks were examined. Plasma concentrations of zotepine were significantly increased after coadministration of diazepam (P < 0.05). Consequently, it is suggested that neither smoking nor CYP2C19 status affects the metabolism of zotepine. The elevation in plasma concentrations of zotepine after coadministration of diazepam may be a result of competitive inhibition of zotepine metabolism by diazepam via other isoenzyme than CYP2C19, e.g., CYP3A4. Received: 25 March 1996/Final version: 28 May 1996 |
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Keywords: | Zotepine Metabolism Smoking CYP2C19 Diazepam |
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