Pharmacokinetics of olanzapine in Chinese male schizophrenic patients with various smoking behaviors

Tzu Hua Wu, Chih Chiang Chiu, Winston W. Shen, Fang Wei Lin, Li Hsuan Wang, Hsiang Yu Chen, Mong Liang Lu

研究成果: 雜誌貢獻文章同行評審

27 引文 斯高帕斯(Scopus)

摘要

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 (≥ 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 Cmax 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.
原文英語
頁(從 - 到)1889-1893
頁數5
期刊Progress in Neuro-Psychopharmacology and Biological Psychiatry
32
發行號8
DOIs
出版狀態已發佈 - 十二月 12 2008

ASJC Scopus subject areas

  • 藥理
  • 生物精神病學

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