Comparative Pharmacology
Head-to-head clinical analysis: DARUNAVIR AND RITONAVIR versus EVOTAZ.
Peer-Reviewed Evidence
Head-to-head clinical analysis: DARUNAVIR AND RITONAVIR versus EVOTAZ.
DARUNAVIR AND RITONAVIR vs EVOTAZ
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
Darunavir is a protease inhibitor that binds to the HIV-1 protease active site, preventing cleavage of viral polyproteins into functional proteins, leading to immature, non-infectious virions. Ritonavir is a potent CYP3A4 inhibitor that increases darunavir plasma concentrations by inhibiting its metabolism.
EVOTAZ is a fixed-dose combination of atazanavir, an HIV-1 protease inhibitor, and cobicistat, a CYP3A inhibitor. Atazanavir inhibits HIV-1 protease, preventing cleavage of viral polyproteins and resulting in immature, non-infectious virions. Cobicistat increases systemic exposure of atazanavir by inhibiting CYP3A-mediated metabolism.
Darunavir 800 mg orally once daily plus ritonavir 100 mg orally once daily in treatment-naïve patients. In treatment-experienced patients with at least one darunavir resistance-associated mutation, darunavir 600 mg plus ritonavir 100 mg orally twice daily.
1 tablet (300 mg atazanavir and 150 mg cobicistat) orally once daily with food.
None Documented
None Documented
Darunavir: ~15 hours (range 10-31 h) when boosted with ritonavir; allows once-daily dosing. Ritonavir: ~3-5 hours (administered as booster).
Cobicistat: terminal half-life approximately 3–4 hours; atazanavir: terminal half-life approximately 7 hours (range 5–12 hours) at steady state when boosted with cobicistat. The short half-life of cobicistat necessitates once-daily dosing with atazanavir to maintain therapeutic concentrations.
Darunavir: 79.5% fecal (primarily as unchanged drug), 13.9% renal (mostly metabolites). Ritonavir: 86.4% fecal, 11.3% renal.
Cobicistat: primarily hepatic metabolism (CYP3A4) and biliary/fecal excretion; <7% excreted unchanged renally. Atazanavir: primarily biliary/fecal excretion as unchanged drug and metabolites (79–88%); renal excretion accounts for <7%.
Category A/B
Category C
Protease Inhibitor
Protease Inhibitor