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 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.
Chiu
Chih-Chiang
CC
Laboratory of Biological Psychiatry, Taipei City Psychiatric Center, Taipei, Taiwan.
Lane
Hsien-Yuan
HY
Huang
Ming-Chyi
MC
Liu
Hui-Ching
HC
Jann
Michael W
MW
Hon
Yuen-Yi
YY
Chang
Wen-Ho
WH
Lu
Mong-Liang
ML
D000328:Adult; D019540:Area Under Curve; D001569:Benzodiazepines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D016666:Fluvoxamine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D000077152:Olanzapine; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012907:Smoking; D013624:Taiwan / Q000208:ethnology
D001569:Benzodiazepines; D000077152:Olanzapine; D016666:Fluvoxamine