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Nonlinear mixed\u2010effects modeling was used to determine PPK characteristics of perphenazine. One\u2010 and 2\u2010compartment models with various random effect implementations and mixture distributions were evaluated. Objective function values and goodness\u2010of\u2010fit plots were used as model selection criteria. Age, weight, sex, race, smoking, and concomitant medications were evaluated as covariates. A 1\u2010compartment linear model with proportional error best described the data. The population mean clearance and volume of distribution for perphenazine were 483 L\/h and 18 200 L, respectively. Race and smoking status had significant impacts on perphenazine clearance estimates. In addition, the estimated population mean clearance was 48% higher in nonsmoking African Americans than in nonsmoking other races (512 L\/h vs 346 L\/h). Active smokers eliminated perphenazine 159 L\/h faster than nonsmokers in each race. 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