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Objevtive:To study the population pharmacokinetics of clozapine conventional tablets and disintegrating tablets in Chinese healthy volunteers.Methods:Fourty-two Chinese healthy volunteers were given 25mg clozapine conventional tablets and disintegrating tablets respectively, and the plasma was collected at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 60 hours after administration.HPLC-MS/MS was used to determine the plasma concentrations of clozapine.The population pharmacokinetic parameters were estimated by nonlinear mixed effect model (NONMEM).Results:A two-compartment model with zero-order and first-order parallel absorption process was built as the structural model.The population system clearance and central volume of distribution of clozapine were 43.6L·h-1 and 13.5L, respectively.The distribution clearance between central and peripheral compartments and peripheral volume of distribution were 123L· h-1 and 658L, respectively.The first-order absorption rate constant was 0.43 h-1 and the fraction of zero-order absorption was 0.65%.No significance was found between the parameters of the conventional tablets and the disintegrating tablets.Conclusion:The population pharmacokinetic parameters of clozapine conventional tablets and disintegrating tablets were suitable for individual therapy.