Abstract | OBJECTIVE: 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. METHODS: 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. RESULTS:
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 clearance and reduced oral bioavailability. Nelfinavir combined with saquinavir reduced apparent oral clearance, increasing saquinavir exposure in children [steady-state geometric mean AUC(0-24 h), 11,070 ng x h/ml; C(8h,SS), 380 ng/ml] to levels that approach those observed in adults. A significant correlation between average trough concentration and sustained viral load suppression was observed in children. The apparent threshold for maintaining viral load suppression was a mean trough saquinavir concentration above 200 ng/ml. CONCLUSIONS:
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Authors | Sibylle Grub, Patricia Delora, Eric Lüdin, Frank Duff, Courtney V Fletcher, Richard C Brundage, Mark W Kline, Nancy R Calles, Heidi Schwarzwald, Karin Jorga |
Journal | Clinical pharmacology and therapeutics
(Clin Pharmacol Ther)
Vol. 71
Issue 3
Pg. 122-30
(Mar 2002)
ISSN: 0009-9236 [Print] United States |
PMID | 11907486
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
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Chemical References |
- Blood Proteins
- HIV Protease Inhibitors
- Nelfinavir
- Saquinavir
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Topics |
- Adolescent
- Area Under Curve
- Blood Proteins
(metabolism)
- Child
- Child, Preschool
- Drug Administration Schedule
- Drug Therapy, Combination
- HIV Infections
(drug therapy, metabolism)
- HIV Protease Inhibitors
(pharmacokinetics, pharmacology, therapeutic use)
- Humans
- Nelfinavir
(pharmacokinetics, therapeutic use)
- Randomized Controlled Trials as Topic
- Saquinavir
(pharmacokinetics, pharmacology, therapeutic use)
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