Dose-dependent alternations in the pharmacokinetics of olanzapine during coadministration of fluvoxamine in patients with schizophrenia

Chih Chiang Chiu, Hsien Yuan Lane, Ming Chyi Huang, Hui Ching Liu, Michael W. Jann, Yuen Yi Hon, Wen Ho Chang, Mong Liang Lu

研究成果: 雜誌貢獻文章

20 引文 (Scopus)

摘要

Olanzapine, an atypical antipsychotic agent, is a substrate of the cytochrome P4501A2 (CYP1A2) enzyme. Administration of a potent CYP1A2 inhibitor (eg, fluvoxamine) may alter the pharmacokinetics of olanzapine. This study investigated the pharmacokinetic interactions between olanzapine and fluvoxamine in patients with schizophrenia. Ten male smokers were administrated a single dose of olanzapine 10 mg at baseline, followed by 2 weeks of fluvoxamine 50 mg/day and another 2 weeks of fluvoxamine 100 mg/day. Olanzapine 10 mg was given at day 10 during each fluvoxamine treatment. After pretreatment with fluvoxamine, the area under the curve, maximal plasma concentration, and half-time of olanzapine were significantly increased by 30% to 55%, 12% to 64%, and 25% to 32%, respectively. Volume of distribution and apparent clearance were significantly reduced by 4% to 26% and 26% t O 38%, respectively, after administration of fluvoxamine. Increases in area under the plasma concentration-time curve from time O to infinity appear to be dose dependent. Presumably, altered olanzapine pharmacokinetics are attributed to the inhibition of CYP1A2. Patients treated with the combination of olanzapine and fluvoxamine should be monitored carefully.

原文英語
頁(從 - 到)1385-1390
頁數6
期刊Journal of Clinical Pharmacology
44
發行號12
DOIs
出版狀態已發佈 - 十二月 2004

指紋

olanzapine
Fluvoxamine
Schizophrenia
Pharmacokinetics
Cytochromes
Antipsychotic Agents
Area Under Curve

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

引用此文

Dose-dependent alternations in the pharmacokinetics of olanzapine during coadministration of fluvoxamine in patients with schizophrenia. / Chiu, Chih Chiang; Lane, Hsien Yuan; Huang, Ming Chyi; Liu, Hui Ching; Jann, Michael W.; Hon, Yuen Yi; Chang, Wen Ho; Lu, Mong Liang.

於: Journal of Clinical Pharmacology, 卷 44, 編號 12, 12.2004, p. 1385-1390.

研究成果: 雜誌貢獻文章

Chiu, Chih Chiang ; Lane, Hsien Yuan ; Huang, Ming Chyi ; Liu, Hui Ching ; Jann, Michael W. ; Hon, Yuen Yi ; Chang, Wen Ho ; Lu, Mong Liang. / Dose-dependent alternations in the pharmacokinetics of olanzapine during coadministration of fluvoxamine in patients with schizophrenia. 於: Journal of Clinical Pharmacology. 2004 ; 卷 44, 編號 12. 頁 1385-1390.
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abstract = "Olanzapine, an atypical antipsychotic agent, is a substrate of the cytochrome P4501A2 (CYP1A2) enzyme. Administration of a potent CYP1A2 inhibitor (eg, fluvoxamine) may alter the pharmacokinetics of olanzapine. This study investigated the pharmacokinetic interactions between olanzapine and fluvoxamine in patients with schizophrenia. Ten male smokers were administrated a single dose of olanzapine 10 mg at baseline, followed by 2 weeks of fluvoxamine 50 mg/day and another 2 weeks of fluvoxamine 100 mg/day. Olanzapine 10 mg was given at day 10 during each fluvoxamine treatment. After pretreatment with fluvoxamine, the area under the curve, maximal plasma concentration, and half-time of olanzapine were significantly increased by 30{\%} to 55{\%}, 12{\%} to 64{\%}, and 25{\%} to 32{\%}, respectively. Volume of distribution and apparent clearance were significantly reduced by 4{\%} to 26{\%} and 26{\%} t O 38{\%}, respectively, after administration of fluvoxamine. Increases in area under the plasma concentration-time curve from time O to infinity appear to be dose dependent. Presumably, altered olanzapine pharmacokinetics are attributed to the inhibition of CYP1A2. Patients treated with the combination of olanzapine and fluvoxamine should be monitored carefully.",
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