Physiologically-based pharmacokinetic modeling for optimal dosage prediction of olaparib when co-administered with CYP3A4 modulators and in patients with hepatic/renal impairment
- Resource Type
- article
- Authors
- Dongmei Gao; Guopeng Wang; Honghai Wu; Jiawei Ren
- Source
- Scientific Reports, Vol 13, Iss 1, Pp 1-15 (2023)
- Subject
- Medicine
Science
- Language
- English
- ISSN
- 2045-2322
Abstract This study aimed to develop a physiologically-based pharmacokinetic (PBPK) model to predict the maximum plasma concentration (Cmax) and trough concentration (Ctrough) 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 Cmax (