Rosuvastatin PBPK Modeling: Incorporating Liver Concentrations and Effects of Ethnicity, Genetic Polymorphisms, Lactone Formation, DDI and Pregnancy.

ABSTRACT: Rosuvastatin (RSV), a potent HMG-CoA reductase inhibitor, is widely used for the management of hyperlipidemia and prevention of cardiovascular disease. Its absorption and disposition are primarily transporter-mediated, involving intestinal absorption by OATP2B1 and efflux by BCRP; hepatic uptake by OATP1B1, OATP1B3, OATP2B1, and NTCP; and biliary excretion by BCRP and MRP2. Given its minimal metabolism, RSV serves as a model substrate for transporter-based drug absorption, disposition, and DDI studies. We developed and verified a PBPK model of RSV using a middle-out approach, incorporating extensive in vitro and in vivo data. The model was verified with > 75 datasets, including plasma and hepatic RSV concentrations from PET imaging studies. The model successfully captured RSV PK profiles i

SUBMITTER: Balhara A 

PROVIDER: S-EPMC12706398 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature