Wu Tzu-Hua, Chiu Chih-Chiang, Shen Winston W, Lin Fang-Wei, Wang Li-Hsuan, Chen Hsiang-Yu, Lu Mong-Liang
Department of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, and Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan.
Prog Neuropsychopharmacol Biol Psychiatry. 2008 Dec 12;32(8):1889-93. doi: 10.1016/j.pnpbp.2008.08.022. Epub 2008 Sep 5.
Tobacco consumption has been recognized as a factor mediating the interindividual variations in olanzapine's pharmacokinetics and pharmacodynamics. The primary objective of this study was to describe the dose effect of smoking on the dose-plasma concentration relationship and the pharmacokinetics of oral olanzapine in male schizophrenic patients using high-performance liquid chromatography coupled with electrochemical detector. Twenty-seven male schizophrenic inpatients were recruited and were stratified into the following groups according to smoking behaviors: non-smokers (n=9), light-smokers (1-4 cigarettes per day; n=9), and heavy-smokers (>or=5 cigarettes per day; n=9). Plasma olanzapine concentrations were determined up to 120 h following a single oral dose of 10 mg olanzapine. The pharmacokinetic parameters were calculated by the non-compartment method using WinNonlin software. Results show that there was a significant correlation among non-smokers (n=9; 0.79; p=0.01) or combined with light-smokers (n=18; 0.62; p<0.01) between peak plasma olanzapine concentrations (Cmax) and their individual dose-corrected by body weight, but this correlation did not appear in heavy-smokers. There were no significant differences between non-smokers and light-smokers except for significant decreased AUC0-->120 by 45.1% in light-smokers. The mean C(max) and the mean area under the plasma concentration-time curve from time zero to 120 h (AUC0-->120) of the heavy-smoking patients was 9.3+/-4.3 ng/ml (65.2% reduction compared to the non-smokers) and 302.4+/-167.8 h ng/ml (67.6% reduction compared to the non-smokers), respectively. In summary, a daily consumption of 5 cigarettes is probably sufficient for induction of olanzapine metabolism. Smoking cessation is recommended for olanzapine therapy to have better prediction for therapeutic dosages particularly in heavy-smokers. Compared to non-smokers, heavy-smokers therefore require a 50-100% increase in olanzapine doses. Therapeutic drug monitoring will need to be considered when schizophrenic patients change their smoking behaviors.
烟草消费已被认为是介导奥氮平药代动力学和药效学个体差异的一个因素。本研究的主要目的是使用高效液相色谱结合电化学检测器，描述吸烟对男性精神分裂症患者口服奥氮平的剂量-血浆浓度关系和药代动力学的剂量效应。招募了27名男性精神分裂症住院患者，并根据吸烟行为将其分为以下几组：不吸烟者（n = 9）、轻度吸烟者（每天1 - 4支香烟；n = 9）和重度吸烟者（每天≥5支香烟；n = 9）。在单次口服10 mg奥氮平后，测定长达120小时的血浆奥氮平浓度。使用WinNonlin软件通过非房室方法计算药代动力学参数。结果显示，在不吸烟者（n = 9；r = 0.79；p = 0.01）或与轻度吸烟者合并（n = 18；r = 0.62；p < 0.01）中，血浆奥氮平峰浓度（Cmax）与其经体重校正的个体剂量之间存在显著相关性，但在重度吸烟者中未出现这种相关性。除轻度吸烟者的AUC0→120显著降低45.1%外，不吸烟者和轻度吸烟者之间无显著差异。重度吸烟患者的平均C(max)和血浆浓度-时间曲线从零到120小时的平均面积（AUC0→120）分别为9.3±4.3 ng/ml（与不吸烟者相比降低65.2%）和302.4±167.8 h ng/ml（与不吸烟者相比降低67.6%）。总之，每天吸食5支香烟可能足以诱导奥氮平代谢。建议在奥氮平治疗期间戒烟，以便更好地预测治疗剂量，尤其是在重度吸烟者中。因此，与不吸烟者相比，重度吸烟者需要将奥氮平剂量增加50 - 100%。当精神分裂症患者改变吸烟行为时，需要考虑进行治疗药物监测。
