Oral delivery of HIV-protease inhibitors

Strategies for optimizing the oral delivery of HIV-protease inhibitors draw from drug discovery efforts in molecular design, drug development tools in dosage formulation, and dosage regimen considerations in clinical medicine . This review outlines the evolution of these strategies for drugs that hav e been approved for human use, drug candidates still in development, and mo lecules that are no longer in development but from which valuable delivery information was obtained. Molecular design for obtaining desirable pharmaco kinetics following oral administration primarily involved maximizing aqueou s solubility and minimizing first-pass metabolism. Optimization of molecula r design for oral drug delivery purposes is tempered by additional consider ations for drug potency, toxicity, potential for interactions, and developm ent of viral resistance. Strategies for improving oral bioavailability thro ugh dosage formulation use information from the effects of coadministered m eals on drug plasma levels. Patient adherence to dosage regimens remains a major issue in assuring effective oral drug treatment and in preventing the development of resistance. Progress has been made in clinical studies wher e improved oral bioavailability and reductions in drug plasma level variabi lity have been achieved with appropriate dosage regimen adjustment.