Metabolism and Excretion
- Eliminated mainly by hepatic metabolism and subsequent biliary excretion
- Metabolic pathways: CYP3A4 and CYP2C9
- Ketoconazole, a 3A4 inhibitor, led to a 2-fold increase in bosentan exposure
- Inhibition of 2C9 is not expected to exert a greater effect than ketoconazole
- CsA, a nonspecific inhibitor of transporters, markedly increased bosentan exposure