Pharmacokinetic variability and strategy for therapeutic drug monitoring of saquinavir (SQV) in HIV-1 infected individuals.
OBJECTIVE
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(R)) 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.
Regazzi
M B
MB
Department of Infectious Diseases, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.
Villani
P
P
Maserati
R
R
Cocchi
L
L
Giacchino
R
R
Burroni
D
D
Rettani
M
M
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D016903:Drug Monitoring; D015497:HIV-1; D006801:Humans; D008875:Middle Aged; D019258:Saquinavir / Q000493:pharmacokinetics*
D019258:Saquinavir