| Title | Population Pharmacokinetics of Perphenazine in Schizophrenia Patients From CATIE: Impact of Race and Smoking. | | Author(s) | Jin Y, Pollock BG, Coley K, Miller D, Marder SR, Florian J, Schneider L, Lieberman J, Kirshner M, Bies RR | | Institution | University of Pittsburgh. | | Source | J Clin Pharmacol 2009 Oct 20. | | Abstract | The goal of the study was to characterize population pharmacokinetics (PPK) for perphenazine in patients with schizophrenia from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). Patients (n = 156) received 8 to 32 mg of perphenazine daily for 14 to 600 days for a total of 421 plasma concentrations measurements. Nonlinear mixed-effects modeling was used to determine PPK characteristics of perphenazine. One- and 2-compartment models with various random effect implementations and mixture distributions were evaluated. Objective function values and goodness-of-fit plots were used as model selection criteria. Age, weight, sex, race, smoking, and concomitant medications were evaluated as covariates. A 1-compartment 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. Clearances for smoking African Americans versus smokers in other races were 671 L/h versus 505 L/h, respectively. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19843655 |
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