< .001). In Asian countries, average clozapine doses are lower than 300 mg/day. After sex and smoking stratification in 5 Asian samples with clozapine concentrations, the clozapine dose required to reach 350 ng/ml in female non-smokers ranged from 145 to 189 mg/day and in male smokers, from 259 to 294 mg/day. Thus, in Asian patients with average metabolism (with no inducers other than smoking, with no inhibitors, and in the absence of extreme obesity), the dose needed for clinical response may range between 150 mg/day for female non-smokers to 300 mg/day for male smokers. Clozapine levels may help personalize dosing in clozapine poor metabolizers (PMs) and ultrarapid metabolizers (UMs). Asian PMs may need very low doses (50-150 mg/day) to obtain therapeutic concentrations. About 10% (range 2-13%) of Asians are genetic PM cases. Other PMs are patients taking CYP1A2 inhibitors such as fluvoxamine, oral contraceptives, and valproate. Temporary clozapine PM status may occur during severe systemic infections/inflammations with fever and C-reactive protein (CRP) elevations. Asian UMs include patients taking potent inducers such as phenytoin, and rarely, valproate.
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León et al. (2019) studied this question.
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