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  • Title: Protease inhibitor update.
    Author: Colvin R, Haas G.
    Journal: Common Factor; 1995 Apr; (no 10):15. PubMed ID: 11362340.
    Abstract:
    New clinical trial developments surrounding anti-HIV compounds, known as protease inhibitors, are discussed for the following drugs: Merck (MK-639), Searle (SC512151), Abbott (ABT-538), Hoffman LaRoche (Saquinavir), Agouron (AG-1343), and Vertex (VX-478). Merck's MK-639 shows marked reductions of HIV in blood, but resistance appears after six months. Side effects have been minimal, the most severe of which is the brief appearance of hyperbilirubinemia. Searle is stopping clinical development of SC512151 because of the drug's lack of anti-viral effect. Preliminary clinical data on Abbott's ABT-538 are promising, based on trials showing rises in CD4 counts, and evidence of very good bioavailability compared with other protease inhibitors. Saquinavir, the longest tested protease inhibitor, shows an ability to cause a two-fold reduction in HIV RNA plasma levels. Supplies of saquinavir are low. Roche intends to apply for accelerated approval of saquinavir in 1995. AG-1343 and VX-478 are just starting clinical trials, however, preclinical trials of AG-1343 show excellent bioavailability and pharmacokinetics.
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