Optimizing the dosing regimen of aripiprazole microspheres by popu-lation pharmacokinetic modeling and simulation
10.12092/j.issn.1009-2501.2025.04.007
- VernacularTitle:基于群体药动学模型的阿立哌唑微球给药方案研究
- Author:
Qingheng MENG
1
;
Zhihui HAN
;
Qi LEI
;
Bin CHEN
;
Xia YIN
;
Haitang HU
;
Hongxia LIU
;
Qingshan ZHENG
;
Ling XU
;
Qin HUANG
Author Information
1. 上海中医药大学药物临床研究中心,上海 201203
- Publication Type:Journal Article
- Keywords:
aripiprazole;
microspheres;
popula-tion pharmacokinetics;
modeling and simulation
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2025;30(4):493-500
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To optimize the clinical dosage and administration regimen of a novel long-acting injectable aripiprazole microsphere(LZMT05)using plasma concentration data from two clinical trials.METHODS:Plasma concentrations were collected from 196 schizophrenia patients administered LZMT05,and a population pharmacokinetic(Pop-PK)model was developed.The therapeutic window was defined as the steady-state trough-to-peak concentration range(94.0-534 ng/mL)of oral ar-ipiprazole.Multiple clinical scenarios were simulat-ed to identify the optimal regimen.RESULTS:A one-compartment model with dual first-order ab-sorption and first-order elimination characterized LZMT05 pharmacokinetics.Covariates like sex and CYP2D6 genotype were integrated into the final model.Simulations demonstrated that switching from 10 mg oral aripiprazole to 350 mg LZMT05 ev-ery 4 weeks sustained concentrations within the therapeutic window with minimal peak-to-trough fluctuations.CONCLUSION:The PopPK-guided opti-mized LZMT05 regimen maintained drug exposure within the therapeutic window,suggesting favor-able efficacy and safety.
