Single- and multiple-dose pharmacokinetics, safety, and tolerability of Aripiprazole once-monthly, long-acting intramuscular injection for Chinese adults with schizophrenia.

Abstract

Background: Aripiprazole once-monthly (AOM), a long-acting injectable antipsychotic, is increasingly used in managing schizophrenia. However, to date, there has been no disclosure of pharmacokinetic data for AOM long-acting injection in the Chinese population. The present study aimed to evaluate the pharmacokinetics of AOM of Chinese patients with schizophrenia.

Methods: The single-administration part of the study was single-center and multiple-dose, in which 300/400-mg AOM was administered to 24 patients with schizophrenia. In the multiple-administration part of the study, 400-mg of AOM was administered once every 4 weeks for 20 consecutive weeks to 12 subjects. Pharmacokinetic parameters (e.g., e.g., Cmax, tmax, AUC0-∞, t1/2, and CL/F) were derived via non-compartmental analysis using actual sampling times, with bootstrap-derived confidence intervals for non-normal data. Safety evaluation included monitoring of adverse events (AEs), physical examinations, vital signs, and clinical laboratory tests.

Results: Following single administration of AOM (300-mg or 400-mg), maximum plasma concentration (C_max) values of aripiprazole were 85.05 ± 42.11 and 175.25 ± 67.84 ng/mL, respectively; median times to achieve C_max (t_max) were 816.17 and 588.84 h, respectively; and elimination half-life (t_1/2) values were 647.18 ± 234.59 and 547.17 ± 258.48 h, respectively. Following multiple administration of AOM, the C_max of aripiprazole was 270.18 ± 113.37 ng/mL, the median t_max was118.83, and the t_1/2 was 1138.78 ± 998.77 h. In vivo exposure to aripiprazole increased with the AOM dose. No severe AEs were observed in single- or multiple-administration studies.

Conclusions: The pharmacokinetics of AOM support its clinical use as a 4-week injectable regimen, with favorable tolerability and safety profiles observed in Chinese patients with schizophrenia.

Trial registration: ClinicalTrials.gov Identifier: Single-administration NCT03287505 first submitted on 15 May 2017, Multiple-administration NCT03285503 first submitted on 11 Sep 2017.