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ABT-538 is a potent inhibitor of human immunodeficiency virus protease and has high oral bioavailability in humans.

Abstract：

: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.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Kempf DJ,Marsh KC,Denissen JF,McDonald E,Vasavanonda S,Flentge CA,Green BE,Fino L,Park CH,Kong XP

doi

10.1073/pnas.92.7.2484

subject

Has Abstract,Author List Incomplete

pub_date

1995-03-28 00:00:00

pages

2484-8

issue

7

eissn

0027-8424

issn

1091-6490

journal_volume

92

pub_type

杂志文章

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