Ritonavir (ABT 538) is a peptidomimetic agent that inhibits both HIV-1 and HIV-2 proteases. Ritonavir is highly inhibited by serum proteins but boosts the effect of other HIV proteases by blocking their degradation by cytochrome P450.

Ritonavir is a potent inhibitor of CYP3A-mediated biotransformation (terfenadine hydroxylation, IC50 of 0.14 mM; 17alpha-ethynylestradiol 2-hydroxylation, IC50 of 2 mM; nifedipine oxidation, IC50 of 0.07 mM).Ritonavir is a a potent inhibitor of CYP3A4-mediated testicular 6β-hydroxylation (Ki: 19 nM), and also inhibited hydroxylation by toluenesulfonylurea (IC50: 4.2 μM).Ritonavir also inhibited CYP2D6 (IC50: 2.5 mM) and CYP2C9/10 (IC50: 8.0 mM)-mediated responses.Ritonavir Ritonavir increased the cellular activity of uninfected human PBMC cultures.Ritonavir inhibited p-glycoprotein-mediated saquinavir solubilization (IC50: 0.2 μM), suggesting that Ritonavir has a high affinity for p-glycoprotein.Ritonavir significantly inhibited the metabolism of human hepatic microsomes ABT-378 (Ki: 13 nM). Ritonavir binding to ABT-378 ( in 3:1 and 29:1 ratios) was able to inhibit CYP3A (IC50: 1.1 and 4.6 μM). In cultures of uninfected human PBMCs, Ritonavir significantly reduced the susceptibility of PBMCs to apoptosis (associated with low levels of caspase-1 expression), decreased caspase-3 activity, and reduced membrane-bound protein staining. Ritonavir inhibited the induction of tumor necrosis factor produced by PBMCs and monocytes at nontoxic concentrations in a time- and dose-dependent manner.