Physiologically-based pharmacokinetic modeling for optimal dosage prediction of olaparib when co-administered with CYP3A4 modulators and in patients with hepatic/renal impairment.

ABSTRACT: This study aimed to develop a physiologically-based pharmacokinetic (PBPK) model to predict the maximum plasma concentration (C_max) and trough concentration (C_trough) at steady-state of olaparib (OLA) in Caucasian, Japanese and Chinese. Furthermore, the PBPK model was combined with mean and 95% confidence interval to predict optimal dosing regimens of OLA when co-administered with CYP3A4 modulators and administered to patients with hepatic/renal impairment. The dosing regimens were determined based on safety and efficacy PK threshold C_max (< 12,500 ng/mL) and C_trough (772-2500 ng/mL). The population PBPK model for OLA was successfully developed and validated, demonstrating good consistency with clinically observed data. The ratios of predicted to

SUBMITTER: Gao D 

PROVIDER: S-EPMC10519932 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature