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

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.