Abstract
The development of inhibitors of HIV protease for the chemotherapy of AIDS has been hampered by the poor pharmacokinetic profile of most inhibitors due to their peptidomimetic nature. Recently, substantial progress in the identification of agents with improved properties has been realized. This Perspective contrasts the preclinical pharmacokinetic parameters of a variety of HIV protease inhibitors with significant oral bioavailability. Inhibitors with high oral Cmax/in vitro EC50 ratios have shown substantial suppression of HIV in vivo. The relationship between the structural and physicochemical features and the pharmacokinetic behavior of peptidomimetic inhibitors is discussed.
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