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Examination of the structural basis for antiviral activity, oral pharmacokinetics, and hepatic metabolism among a series of symmetry-based inhibitors of the human immunodeficiency virus (HIV) protease led to the discovery of ABT-538, a promising experimental drug for the therapeutic intervention in acquired immunodeficiency syndrome (AIDS). ABT-538 exhibited potent in vitro activity against laboratory and clinical strains of HIV-1 [50% effective concentration (EC50) = 0.022-0.13 microM] and HIV-2 (EC50 = 0.16 microM). Following a single 10-mg/kg oral dose, plasma concentrations in rat, dog, and monkey exceeded the in vitro antiviral EC50 for > 12 h. In human trials, a single 400-mg dose of ABT-538 displayed a prolonged absorption profile and achieved a peak plasma concentration in excess of 5 micrograms/ml. These findings demonstrate that high oral bioavailability can be achieved in humans with peptidomimetic inhibitors of HIV protease.

ABT-538 is a potent inhibitor of human immunodeficiency virus protease and has high oral bioavailability in humans., Kempf DJ, Marsh KC, Denissen JF, McDonald E, Vasavanonda S, Flentge CA, Green BE, Fino L, Park CH, Kong XP, et al., Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2484-8. PMID:7708670

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Categories: HIV-1 Protease | HIV-1 retropepsin | Human immunodeficiency virus 1 | Single protein | Kong, X P. | Nienaber, V. | Park, C H. | Aspartic proteinase | Aspartyl protease | Hiv | Hydrolase