Clozapine nanoencapsulation improves pharmacokinetic parameters: a population analysis

Our aim was to analyze the clozapine plasma data from nanocapsules with different surface characteristics using population pharmacokinetic approach (Monolix, v. 2018R2, Lixoft). A data set with 384 entries from 25 rats divided into 4 groups (CZP Free, NC1, NC2 or NC3) was used. The different coatings were considered the only covariates. Different compartments have been tested to find the best model. A model of a central compartment and two peripherals with linear alteration process describes the best behavior of plasma clozapine. Statistically, there was an increase in clearance for NC1, while for NC3 it decreased. V1 and Q3 showed a reduction for NC3 (beta=-1.25 and -2.55, respectively). The results demonstrated that nanoencapsulation altered some pharmacokinetic parameters, suggesting that it is an interesting system to be employed in clozapine pharmacotherapy.