title: Pharmacokinetics of olanzapine in Chinese male schizophrenic patients with various smoking behaviors.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, and Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan.
authors.forename: Tzu-Hua
authors.initials: TH
authors.lastname: Wu
authors.forename: Chih-Chiang
authors.initials: CC
authors.lastname: Chiu
authors.forename: Winston W
authors.initials: WW
authors.lastname: Shen
authors.forename: Fang-Wei
authors.initials: FW
authors.lastname: Lin
authors.forename: Li-Hsuan
authors.initials: LH
authors.lastname: Wang
authors.forename: Hsiang-Yu
authors.initials: HY
authors.lastname: Chen
authors.forename: Mong-Liang
authors.initials: ML
authors.lastname: Lu
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D044466:Asian People / Q000235:genetics; D001569:Benzodiazepines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy; D012565:Schizophrenic Psychology; D012907:Smoking / Q000097:blood; D013624:Taiwan; D013997:Time Factors; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine