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

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Abstract
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®) were 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 (C3 h ) and AUC(0,8h).Conclusions This study shows that C3 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.