Drug intelligence / Profile preview

danoprevir + ritonavir + cyclosporine

Development stage
Unknown
Lead developer
Roche
Modality
Small Molecules
Administration
Oral, Intravenous
01

Overview

Danoprevir + ritonavir + cyclosporine is an experimental combination of three drugs investigated for pharmacokinetic and drug-drug interaction studies, primarily in the context of hepatitis C virus (HCV) infection. **Danoprevir** is a second-generation, potent macrocyclic inhibitor of the HCV NS3/4A serine protease, a viral protease essential for viral replication and maturation. **Ritonavir** is a small molecule used here as a pharmacological enhancer; it inhibits CYP3A4-mediated metabolism, thereby increasing plasma concentrations of danoprevir. **Cyclosporine** is an immunosuppressant that inhibits calcineurin and thus T cell activation, but in this context is of interest primarily for its inhibitory effects on cytochrome P450 (CYP3A4) and organic anion-transporting polypeptide (OATP) transporters, affecting the metabolism and exposure of danoprevir and ritonavir. Studies have focused on the significant pharmacokinetic interactions among these agents, particularly marked increases in danoprevir and ritonavir exposure when combined with cyclosporine due to metabolic and transporter inhibition. This combination is not an approved therapy but has been the subject of clinical pharmacology research for managing drug interactions in patients treated for chronic HCV infection, especially those who also require immunosuppression (e.g., post-transplant)[1][2][3][4].

02

Targets

OATP1B1 (Organic anion transporting polypeptide 1B1)CYP3A4 (Cytochrome P450 3A4)SLCO1B3 (Organic anion transporting polypeptide 1B3)PPIA (Peptidyl-prolyl cis-trans isomerase A)NS3/4A (Hepatitis C virus nonstructural protein 3/4A serine protease)CN (Calcineurin)

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