title: Pharmacokinetic variability and strategy for therapeutic drug monitoring of saquinavir (SQV) in HIV-1 infected individuals.
abstract: 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.
authors.affiliation: Department of Infectious Diseases, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.
authors.forename: M B
authors.initials: MB
authors.lastname: Regazzi
authors.forename: P
authors.initials: P
authors.lastname: Villani
authors.forename: R
authors.initials: R
authors.lastname: Maserati
authors.forename: L
authors.initials: L
authors.lastname: Cocchi
authors.forename: R
authors.initials: R
authors.lastname: Giacchino
authors.forename: D
authors.initials: D
authors.lastname: Burroni
authors.forename: M
authors.initials: M
authors.lastname: Rettani
mesh_terms: 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*
chemical_list: D019258:Saquinavir