A semi-mechanistic pharmacokinetic model of saquinavir combined with itraconazole in HIV-1-positive patients

The mechanism of drug-drug interaction between saquinavir, a protease inhibitor used effectively for HIV/AIDS treatment, and itraconazole, an azole antifungal agent, is hypothesized to involve competitive inhibition at CYP3A4 enzyme, an important drug metabolizing enzyme in humans. The resulting interaction between these CYP3A4 substrates can be utilized clinically as a pharmacokinetic booster for prolonging saquinavir dosing regimen and/or decreasing saquinavir dose requirement in HIV/AIDS patients. To quantitatively describe this specific drug-drug interaction, based on the existing data, we aimed to develop a mathematical model incorporated with the competitive inhibition phenomena. PlotDigitizer was used to extract data from literature. Advance Continuous Simulating Language Extreme (ACSLX), a FORTRAN-based computer program, was employed as our developing tool. Our computer model simulations could successfully describe concentration-time course of saquinavir from selected pharmacokinetic studies in HIV-1-positive patients. To extend the model´s utility as an aid in saquinavir dosage regimens, the developed model may be applied to other HIV/AIDS patients in genuine clinical settings.