Pharmacokinetic variability and strategy for therapeutic drug monitoring of saquinavir (SQV) in HIV-1 infected individuals

Aims. To investigate the pharmacokinetic profile of the protease inhibitor saquinavir (SQV) after multiple doses in HIV-positive patients and to evaluate the possibility of predicting total body exposure of SQV from concentrations determined at single time points. Methods. Twenty HIV-positive patients on steady-state treatment with SQV (Hard-Gel-Capsule, Invirase®) enrolled in this study. Serial blood samples were obtained during a dosing interval. SQV plasma concentrations were determined by high performance liquid chromatography (h.p.l.c.) and pharmacokinetic parameters were determined by noncompartmental techniques. Results. There was a marked interindividual variability in SQV pharmacokinetic parameters with a 11-fold variability in total systemic exposure to SQV, as expressed by AUC(0,8h) values (range: 268-3009 ng ml^-1 h, CV: 69%). The oral clearance shows an interindividual CV of 75%. A strong correlation (r = 0.94) was found between SQV plasma concentration at 3 h (C(3 h)) and AUC(0,8h). Conlusions. This study shows that C(3 h) is a good predictor for total body exposure of SQV and might be useful to predict SQV disposition in HIV-positive patients on steady-state treatment.