HIV drug summary

This is a summary page for compounds under development or approved for treatment of HIV.

NIAID HIV/OI Searchable Chemical Database

Ritonavir; Norvir®; ABT-538
	Ritonavir is a potent protease inhibitor with high oral bioavailability. In rats, following an oral 10 mg/kg dose, ritonavir was 78% bioavailable and had a maximal plasma concentration (Cmax) of 2.62 µM, two hours after dosing. Ritonavir was soluble to 5.3 µg/mL at pH 7.4 and 6.9 µg/mL at pH 4.0 and had a plasma half-life of 1.2 hours, following a 5 mg/kg i.v. dose (1). Ritonavir is also a potent inhibitor of a primary liver drug metabolizing enzyme, CYP-3A4. Kaletra®, a formulation containing both lopinavir and ritonavir, takes advantage of this property by using ritonavir to increase the bioavailability lopinavir (2).
In-vitro Data Cell Strain EC50 IC50 Units TI Reference MT-4 HIV-1(IIIB) 0.025 57 µM 2280 1 PBMC HIV-1(7 CLINICAL ISOLATE) 0.045 (< 0.01-0.13) 49 µM 1089 1 PBMC HIV-1(104 PRETREAT.) 0.023 - µM - 3 PBMC HIV-1(104 D21(PR-V82A))* 0.046 - µM - 3 PBMC HIV-1(131 PRETREAT.) 0.018 - µM - 3 PBMC HIV-1(131 D200(PR-K20K/R,M36I,I54V/I,V82A))^ 0.731 - µM - 3 MT-4 HIV-1(NL4-3) 0.03 - µM - 4 MT-4 HIV-1(NL4-3 P19(PR-I84V,M46I))** 0.18 - µM - 4 MT-4 HIV-1(NL4-3 P22(PR-V82F,I84V,M46I))+ 0.8 - µM - 4 MT-4 HIV-1(NL4-3 (PR-I84V))^^ 0.2 - µM - 4 MT-4 HIV-1(NL4-3 (PR-I84V,M46I))^^ 0.2 - µM - 4 MT-4 HIV-1(NL4-3 (PR-V82F))^^ 0.15 - µM - 4 MT-4 HIV-1(NL4-3 (PR-M46I))^^ 0.02 - µM - 4

References

1. KEMPF, D.J.; MARSH, K.C.; DENISSEN, J.F.; MCDONALD, E.; VASAVANONDA, S.; FLENTGE, C.A.; GREEN, B.E.; FINO, L.; PARK, C.H.; KONG, X.P.; PLATTNER, J.J.; LEONARD, J.M.; NORBECK, D.W.; ET AL., ABT-538 IS A POTENT INHIBITOR OF HUMAN IMMUNODEFICIENCY VIRUS PROTEASE AND HAS HIGH ORAL BIOAVAILABILITY IN HUMANS. PROC NATL ACAD SCI USA 92(7):2484-2488 (1995).
2. SHAM, HL; KEMPF, DJ; MOLLA, A; MARSH, KC; KUMAR, GN; CHEN, C-M; KATI, W; STEWART, K; LAL, R; HSU, A; BETEBENNER, D; KORNEYEVA, M; VASAVANONDA, S; MCDONALD, E; SALDIVAR, A; JAPOUR, AJ; LEONARD, JM; PLATTNER, JJ; NORBECK, DW; ET AL., ABT-378, A HIGHLY POTENT INHIBITOR OF THE HUMAN IMMUNODEFICIENCY VIRUS PROTEASE. ANTIMICROB AGENTS CHEMOTHER 42(12):3218-3224 (1998).
3. MOLLA, A.; KORNEYEVA, M.; GAO Q.; VASAVANONDA, S.; SCHIPPER P.J.; MO, H.-M.; MARKOWITZ, M.;CHERNYAVSKY, T.; NIU, P.; LYONS N.; HSU, A.; GRANNEMAN, G.R.; HO, D.D.; BOUCHER, C.A.B.; LEONARD J.M.; NORBECK, D.W.; KEMPF, D.J., ORDERED ACCUMULATION OF MUTATIONS IN HIV PROTEASE CONFERS RESISTANCE TO RITONAVIR. NATURE MEDICINE 2(7):760-766 (1996).
4. MARKOWITZ, M.; MO, H.; KEMPF, D.J.; NORBECK, D.W.; BHAT, T.N.; ERICKSON, J.W.; HO, D.D., SELECTION AND ANALYSIS OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 VARIANTS WITH INCREASED RESISTANCE TO ABT-538, A NOVEL PROTEASE INHIBITOR. J VIROL 69(2):701-706 (1995).

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