Saquinavir is a suboptimal treatment for children unless used in combination
Graham McKerrow, HIV i-Base
The pharmacokinetics of saquinavir (SQV, Fortovase) in children is different from that of adults, and administration of SQV alone to HIV-infected children will not give consistently efficacious plasma levels, report Swiss researchers.
The best way of improving SQV levels in children is through combination therapy with other protease inhibitors that inhibit SQV metabolism, according to researchers at F Hoffmann-La Roche Ltd in Basel, Switzerland.
Dr Sibylle Grub and colleagues investigated the clinical pharmacologic characteristics of SQV given as a soft gelatine capsule, either alone or in combination with nelfinavir (NFV, Viracept) to children and adolescents with HIV.
They assessed the pharmacokinetics of 50mg/kg SQV three times a day (tid) alone to 14 children and compared the results with those in 13 children given 33mg/kg SQV tid plus 30mg/kg NFV tid. They assessed the results after single dose administration and after short- and long-term administration.
They also investigated the pharmacokinetics of a fixed single dose of 1200mg SQV compared with unrestricted weight-adjusted dosing at 50mg/kg.
The results reported in the March issue of Clinical Pharmacology and Therapeutics show that SQV as the sole protease inhibitor resulted in lower SQV exposure in children and adolescents than that reported in adults treated with 1200mg tid.
The researchers report that this appeared to be attributable to markedly higher apparent oral clearance, potentially as a result of increased systemic clearance and reduced oral bioavailability.
NFV combined with SQV reduced apparent oral clearance, increasing SQV exposure in children to levels that approach those in adults. The researchers write: “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 SQV concentration above 200ng/mL.”
Grub S, Delora P, Ludin E et al. Pharmacokinetics and pharmacodynamics of saquinavir in pediatric patients with human immunodeficiency virus infection. Clin Pharmacol Ther 2002 Mar;71(3):122-30