Ritonavir  (Synonyms: ABT 538; RTV)

Ritonavir (ABT 538) is an inhibitor of HIV protease used to treat HIV infection and AIDS. Ritonavir is also a SARS-CoV 3CL^pro inhibitor with an IC₅₀ of 1.61 μM.

Ritonavir (ABT 538) is an inhibitor of CYP3A4 mediated testosterone 6β-hydroxylation with mean K_i of 19 nM and also inhibits tolbutamide hydroxylation with IC₅₀ of 4.2 μM^[1]. Ritonavir (ABT 538) is found to be a potent inhibitor of CYP3A-mediated biotransformations (nifedipine oxidation with IC₅₀ of 0.07 mM, 17alpha-ethynylestradiol 2-hydroxylation with IC₅₀ of 2 mM; terfenadine hydroxylation with IC₅₀ of 0.14 mM). Ritonavir is also an inhibitor of the reactions mediated by CYP2D6 (IC₅₀=2.5 mM) and CYP2C9/10 (IC₅₀=8.0 mM)^[2]. Ritonavir results in an increase in cell viability in uninfected human PBMC cultures. Ritonavir markedly decreases the susceptibility of PBMCs to apoptosis correlated with lower levels of caspase-1 expression, decreases in annexin V staining, and reduces caspase-3 activity in uninfected human PBMC cultures. Ritonavir inhibits induction of tumor necrosis factor (TNF) production by PBMCs and monocytes in a time- and dose-dependent manner at nontoxic concentrations^[3]. Ritonavir inhibits p-glycoprotein-mediated extrusion of saquinavir with an IC₅₀ of 0.2 μM, indicating a high affinity of ritonavir for p-glycoprotein^[4]. Ritonavir inhibits human liver microsomal metabolism of ABT-378 potently with K_i of 13 nM. Ritonavir combined with ABT-378 (at 3:1 and 29:1 ratios) inhibits CYP3A (IC₅₀=1.1 and 4.6 μM), albeit less potently than Ritonavir (IC₅₀=0.14 μM)^[5].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

720.94

Solid

C₃₇H₄₈N₆O₅S₂

155213-67-5

O=C(N[[email protected]@H](CC1=CC=CC=C1)[[email protected]](C[[email protected]](CC2=CC=CC=C2)NC([[email protected]](C(C)C)NC(N(CC3=CSC(C(C)C)=N3)C)=O)=O)O)OCC4=CN=CS4

Room temperature in continental US; may vary elsewhere.

• [1]. Eagling VA, et al. Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir. Br J Clin Pharmacol. 1997 Aug;44(2):190-4.  [Content Brief]

  [2]. Kumar GN, et al. Cytochrome P450-mediated metabolism of the HIV-1 protease inhibitor ritonavir (ABT-538) in human liver microsomes. J Pharmacol Exp Ther. 1996 Apr;277(1):423-31.  [Content Brief]

  [3]. Weichold FF, et al. HIV-1 protease inhibitor ritonavir modulates susceptibility to apoptosis of uninfected T cells. J Hum Virol. 1999 Sep-Oct;2(5):261-9.  [Content Brief]

  [4]. Drewe J, et al. HIV protease inhibitor ritonavir: a more potent inhibitor of P-glycoprotein than the cyclosporine analog SDZ PSC 833. Biochem Pharmacol. 1999 May 15;57(10):1147-52.  [Content Brief]

  [5]. Kumar GN, et al. Potent inhibition of the cytochrome P-450 3A-mediated human liver microsomal metabolism of a novel HIV protease inhibitor by ritonavir: A positive drug-drug interaction. Drug Metab Dispos. 1999 Aug;27(8):902-8.  [Content Brief]

  [6]. Qi Sun, et al. Bardoxolone and bardoxolone methyl, two Nrf2 activators in clinical trials, inhibit SARS-CoV-2 replication and its 3C-like protease. Signal Transduct Target Ther. 2021 May 29;6(1):212.  [Content Brief]