Indicated in combination with other antiretroviral agents for the treatment of HIV-infection.
Ritonavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Ritonavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.
Mode of Action:
Ritonavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.
Hepatic. Five metabolites have been identified. The isopropylthiazole oxidation metabolite (M-2) is the major metabolite and has antiviral activity similar to that of ritonavir, however, plasma concentrations are low. The cytochrome P450 enzymes CYP3A and CYP2D6 are primarily involved in the metabolism of ritonavir.
Human experience of acute overdose with ritonavir is limited. One patient in clinical trials took ritonavir 1500 mg/day for two days. The patient reported paresthesias which resolved after the dose was decreased. A post-marketing case of renal failure with eosinophilia has been reported with ritonavir overdose. The approximate lethal dose was found to be greater than 20 times the related human dose in rats and 10 times the related human dose in mice.
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