danoprevir + ritonavir + ketoconazole

This is an oral **combination regimen** comprising **danoprevir**, **ritonavir**, and **ketoconazole**. Danoprevir is a highly selective, macrocyclic inhibitor of the hepatitis C virus (HCV) NS3/4A protease; it is metabolized by cytochrome P450 3A (CYP3A). Ritonavir is a potent CYP3A inhibitor used at low doses to boost the pharmacokinetic profile of co-administered CYP3A substrates, such as danoprevir. Ketoconazole is an antifungal agent and also a potent CYP3A inhibitor and substrate. This combination is investigated to evaluate drug-drug interactions due to the shared CYP3A metabolic pathway. In a pharmacokinetic study, ketoconazole modestly increased danoprevir exposure, while ritonavir-boosted danoprevir substantially increased ketoconazole exposure. The regimen was generally well tolerated in healthy subjects[1]. Primary indications: **Hepatitis C virus infection** (investigated pharmacokinetically, not approved as a fixed formulation). The main mechanism of action is direct inhibition of HCV protease (danoprevir). Ritonavir and ketoconazole mainly act as pharmacokinetic enhancers via CYP3A inhibition.