Chiu Chih-Chiang, Lane Hsien-Yuan, Huang Ming-Chyi, Liu Hui-Ching, Jann Michael W, Hon Yuen-Yi, Chang Wen-Ho, Lu Mong-Liang
Laboratory of Biological Psychiatry, Taipei City Psychiatric Center, Taipei, Taiwan.
J Clin Pharmacol. 2004 Dec;44(12):1385-90. doi: 10.1177/0091270004270291.
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.
奥氮平是一种非典型抗精神病药物，是细胞色素P4501A2（CYP1A2）酶的底物。给予强效CYP1A2抑制剂（如氟伏沙明）可能会改变奥氮平的药代动力学。本研究调查了精神分裂症患者中奥氮平和氟伏沙明之间的药代动力学相互作用。10名男性吸烟者在基线时单次服用10mg奥氮平，随后2周每天服用50mg氟伏沙明，再接下来2周每天服用100mg氟伏沙明。在每次氟伏沙明治疗的第10天给予10mg奥氮平。在氟伏沙明预处理后，奥氮平的曲线下面积、最大血浆浓度和半衰期分别显著增加了30%至55%、12%至64%和25%至32%。给予氟伏沙明后，分布容积和表观清除率分别显著降低了4%至26%和26%至38%。从时间0到无穷大的血浆浓度-时间曲线下面积的增加似乎呈剂量依赖性。推测奥氮平药代动力学的改变归因于CYP1A2的抑制。接受奥氮平和氟伏沙明联合治疗的患者应密切监测。
