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

Mario B. Regazzi, Paola Villani, Renato Maserati, Laura Cocchi, Roberto Giacchino, Daniela Burroni, Mauro Rettani

Research output: Contribution to journalArticle

27 Citations (Scopus)

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®) 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.

Original languageEnglish
Pages (from-to)379-382
Number of pages4
JournalBritish Journal of Clinical Pharmacology
Volume47
Issue number4
DOIs
Publication statusPublished - 1999

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Saquinavir
Drug Monitoring
HIV-1
Pharmacokinetics
HIV
Area Under Curve
Protease Inhibitors
Capsules
Gels
High Pressure Liquid Chromatography

Keywords

  • HIV infection
  • Pharmacokinetics
  • Saquinavir

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Pharmacokinetic variability and strategy for therapeutic drug monitoring of saquinavir (SQV) in HIV-1 infected individuals. / Regazzi, Mario B.; Villani, Paola; Maserati, Renato; Cocchi, Laura; Giacchino, Roberto; Burroni, Daniela; Rettani, Mauro.

In: British Journal of Clinical Pharmacology, Vol. 47, No. 4, 1999, p. 379-382.

Research output: Contribution to journalArticle

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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{\circledR}) 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.",
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AU - Giacchino, Roberto

AU - Burroni, Daniela

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