Comparative Pharmacology
Head-to-head clinical analysis: EVOTAZ versus LOPINAVIR AND RITONAVIR.
Peer-Reviewed Evidence
Head-to-head clinical analysis: EVOTAZ versus LOPINAVIR AND RITONAVIR.
EVOTAZ vs LOPINAVIR AND RITONAVIR
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
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.
Lopinavir is a HIV-1 protease inhibitor that prevents cleavage of viral Gag-Pol polyproteins, resulting in immature, non-infectious viral particles. Ritonavir is a potent CYP3A4 inhibitor that increases lopinavir plasma concentrations; at subtherapeutic doses, it also inhibits HIV-1 protease.
1 tablet (300 mg atazanavir and 150 mg cobicistat) orally once daily with food.
Lopinavir/ritonavir 400/100 mg (two tablets of 200/50 mg or 5 mL oral solution 80/20 mg per mL) orally twice daily with food.
None Documented
None Documented
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.
Lopinavir terminal elimination half-life is approximately 5–6 hours (range 4–8 h) when co-administered with ritonavir. Ritonavir half-life is about 3–5 hours. The prolonged half-life of lopinavir in the presence of ritonavir supports twice-daily dosing; steady state is reached within 2–3 days.
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%.
Lopinavir is primarily eliminated via hepatic metabolism (CYP3A4), with <3% excreted unchanged in urine and ~20% excreted unchanged in feces. Ritonavir is also predominantly hepatically metabolized, with <3.5% excreted unchanged in urine and ~86% eliminated in feces (mostly as metabolites).
Category C
Category A/B
Protease Inhibitor
Protease Inhibitor