Individual differences in the pharmacokinetics of clozapine in healthy Chinese adults

Abstract

Introduction: Differences in response to clozapine among patients have received considerable attention. Individual pharmacokinetic differences are a major reason. Objective: The aim of this study was to investigate the pharmacokinetic variability in the blood levels ofclozapine among young, healthy, Chinese male volunteers. Methods: A total of 18 volunteers who received 12.5mg of clozapine participated in the study. Blood samples were measured by using High-Performance Liquid Chromatography-Electrospray ionization tandem mass spectrometry (LC-MS/MS). The major pharmacokinetic parameters were calculated from the plasma concentration-time curve and individual variability was assessed. Results: The findings indicated that the AUC 0-48h, C max and t 1/2 varied 2.9, 2.6, and 2.0 fold, respectively among the individuals even with similar physiological status. Conclusions: Individual differences were obvious among healthy volunteers and greater differences could have been observed if more subjects had been included in the study. Psychiatrists and pharmacists may need to have more patience and pay more attention to high variability in response to clozapine among schizophrenic patients with differences in weight, age, liver function, renal function, and pharmacogenetics.