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Pharmacokinetic variability and strategy for therapeutic drug monitoring of saquinavir (SQV) in HIV‐1 infected individuals
Author(s) -
Regazzi Mario B.,
Villani Paola,
Maserati Renato,
Cocchi Laura,
Giacchino Roberto,
Burroni Daniela,
Rettani Mauro
Publication year - 1999
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1999.00919.x
Subject(s) - saquinavir , pharmacokinetics , pharmacology , dosing , protease inhibitor (pharmacology) , drug , human immunodeficiency virus (hiv) , medicine , antiretroviral therapy , viral load , virology
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 (C 3 h ) and AUC(0,8h). Conclusions 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.