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Dose-Dependent Alternations in the Pharmacokinetics of Olanzapine During Coadministration of Fluvoxamine in Patients With Schizophrenia

From the Laboratory of Biological Psychiatry, Taipei City Psychiatric Center, Taipei, Taiwan (Dr Chiu, Dr Huang); Department of Psychiatry, China Medical University and Hospital, Taichung, Taiwan (Dr Lane); Hung-Chi Psychiatric Hospital, Taipei, Taiwan (Dr Liu); Department of Clinical and Administrative Sciences, Southern School of Pharmacy, Mercer University, Atlanta, Georgia (Dr Jann); Clinical Pharmacokinetics Research Laboratory, Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, Maryland (Dr Hon); Department of Psychiatry, Dalin Tzu-Chi General Hospital and Tzu-Chi University, Hualien, Taiwan (Dr Chang); and Department of Psychiatry, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan (Dr Lu).

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 0 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.

Key Words: Olanzapine • fluvoxamine • drug interactions • schizophrenia

Address for reprints: Mong-Liang Lu, MD, Department of Psychiatry, Taipei Medical University-Wan Fang Hospital, No. 111, Hsin-Long Road, Sec. 3, Taipei, Taiwan.

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