Combined therapy with thioridazine decreases plasma levels of quetiapine inTaiwanese schizophrenic patients.

BACKGROUND: In this study, the authors studied the effect of thioridazine (TDZ) on the pharmacokinetic profile of quetiapine (QTP) in Taiwanese patients with schizophrenia. METHODS: Sixteen subjects with schizophrenia were recruited for this study. The authors pretreated 8 patients with TDZ 50 mg daily continuously given until the end of the study. QTP was administered to all the participants, and their doses were escalated to 300 mg once daily over a 7-day period and maintained for another week. On day 15, blood samples were collected at 12 time points within an 8-hour interval. The authors assayed the plasma levels of QTP with a high-performance liquid chromatography system coupled with ultraviolet detector. RESULTS: Significantly decreased plasma levels of QTP after oral administration were observed in patients comedicated with TDZ compared with the QTP monotherapy group at 1.5, 2, and 2.5 hours, and the P values were 0.046, 0.001, and 0.005, respectively. The Cmax of QTP was significantly lower in the group comedicated with TDZ (776.9 ± 175.2 versus 1452.3 ± 707.5 ng/mL; P = 0.002). The oral clearance of QTP was significantly higher in the combined group than in the monothreapy group (123.3 ± 66.8 versus 60.3 ± 28.5 L/h; P = 0.03). Other pharmacokinetic parameters were not significantly different. CONCLUSIONS: The coadministration of TDZ significantly decreased plasma QTP level and significantly increased the oral clearance of QTP. Although TDZ is switched to QTP, choosing larger doses of QTP for titration may be necessary to avoid the emergence of psychotic symptoms among schizophrenic patients.

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

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.