Predicting Systemic and Liver Bosentan Exposure Using Physiologically-Based Pharmacokinetic Modeling.

ABSTRACT: Bosentan is the first approved oral medication for pulmonary arterial hypertension, yet the black-box warning on its labeling implies a substantial risk of liver injury associated with bosentan exposure. The risk assessment of bosentan-induced liver injury requires a thorough understanding of the underlying mechanisms, for which there is accumulating evidence. Integrating these mechanisms with clinical liver bosentan concentration would enable a more dynamic and relevant risk assessment. This study designed a workflow of physiologically-based pharmacokinetic (PBPK) model development to capture bosentan's hepatic disposition and predict the (intra)hepatic bosentan exposure. Specifically, clinical plasma and excretion data of bosentan were used to minimize the uncertainty in estimating the h

SUBMITTER: Huang MC 

PROVIDER: S-EPMC12521053 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature