Details

Autor(en) / Beteiligte

• Kempf, Dale J.
• Marsh, Kennan C.
• Denissen, Jon F.
• McDonald, Edith
• Vasavanonda, Sudthida
• Flentge, Charles A.
• Green, Brian E.
• Fino, Lynnmarie
• Park, Chang H.
• Kong, Xiang-Peng
• Wideburg, Norman E.
• Saldivar, Ayda
• Ruiz, Lisa
• Kati, Warren M.
• Sham, Hing L.
• Robins, Terry
• Stewart, Kent D.
• Hsu, Ann
• Plattner, Jacob J.
• Leonard, John M.
• Norbeck, Daniel W.

Titel

ABT-538 is a Potent Inhibitor of Human Immunodeficiency Virus Protease and has High Oral Bioavailability in Humans

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1995-03, Vol.92 (7), p.2484-2488

Ort / Verlag

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

Erscheinungsjahr

1995

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 μM] and HIV-2 (EC50= 0.16 μM). Following a single 10-mg/kg oral dose, plasma concentrations in rat, dog, and monkey exceeded the in vitro antiviral EC50for > 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 μg/ml. These findings demonstrate that high oral bioavailability can be achieved in humans with peptidomimetic inhibitors of HIV protease.