Pharmacokinetics and pharmacodynamics of saquinavir in pediatric patients with human immunodeficiency virus infection

Clinical Pharmacology and Therapeutics
Sibylle GrubK Jorga

Abstract

Our objective was to investigate the clinical pharmacologic characteristics of saquinavir given as a soft gelatin capsule, either alone or in combination with nelfinavir, to children and adolescents with human immunodeficiency virus infection. The pharmacokinetics of 50 mg/kg saquinavir 3 times a day (tid) alone versus 33 mg/kg saquinavir tid plus 30 mg/kg nelfinavir tid was assessed after single-dose administration and after short- and long-term administration. The single-dose pharmacokinetics of fixed (1200 mg) versus unrestricted weight-adjusted dosing (50 mg/kg) was also investigated. Saquinavir as the sole protease inhibitor resulted in lower saquinavir exposure in children (steady-state geometric mean area under the concentration-time curve from time zero to 24 hours [AUC (0-24 h)], 5790 ng x h/ml; steady-state concentration 8 hours after drug administration [C(8h,SS)], 65 ng/ml) and adolescents [steady-state geometric mean AUC(0-24 h), 5914 ng x h/ml] than that reported in adults treated with 1200 mg tid [steady-state geometric mean AUC(0-24 h), 21,700 ng x h/ml; C(8h,SS), 223 ng/ml]. This finding appeared to be attributable to markedly higher apparent oral clearance, potentially as a result of increased systemic clearan...Continue Reading

Citations

Sep 12, 2012·Antimicrobial Agents and Chemotherapy·Edward P AcostaChristos J Petropoulos
Sep 10, 2009·Expert Opinion on Drug Metabolism & Toxicology·Charles J L la Porte
May 30, 2009·Pharmacotherapy·Gail D Anderson, Anne M Lynn
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Oct 13, 2005·The Pediatric Infectious Disease Journal·Jintanat AnanworanichUNKNOWN HIV-NAT 017 Study Team
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Sep 19, 2002·The Pediatric Infectious Disease Journal·Sibylle GrubKarin Jorga
Apr 4, 2007·Pediatrics·Peter L HavensDiana M Gibb

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