Pharmacologic characteristics of indinavir, didanosine, and stavudine in human immunodeficiency virus-infected children receiving combination therapy

The use of human immunodeficiency virus (HIV) protease inhibitors in childr en has lagged behind that in adults because of the lack of suitable pediatr ic formulations and information on safe and effective dosing regimens. This study was designed to obtain pharmacokinetic information on indinavir, adm inistered to HIV-infected children also receiving therapy with two nucleosi de agents, and to explore relationships between pharmacokinetic parameters and anti-HIV effect. Indinavir was initiated at a dose of 500 mg/m(2) every 8 h. Plasma indinavir concentrations were measured every 4 weeks; the dose or dosing interval was adjusted to maintain trough concentrations of great er than or equal to 0.1 mg/liter. All children were evaluated clinically at baseline and every 4 weeks. Plasma HIV RNA was quantitated at baseline and at weeks 4, 12, and 24. Eighteen children participated in this study. The average daily dose of indinavir was 2,043 mg/m(2); nine children received i ndinavir at 6-h intervals. Pharmacokinetic characteristics of indinavir (me an +/- standard deviation) were the following: oral clearance, 1.4 +/- 0.5 liters/h/kg; half-life, 1.1 +/- 0.43 h; and trough concentration, 0.29 +/- 0.32 mg/liter, In nine children that completed 24 weeks of therapy, the bas eline-to-week-24 change in HIV RNA level was related to indinavir trough co ncentration and didanosine area under the curve. This study illustrates the ability to obtain pharmacokinetic information from children during routine clinic visits and to use this information to provide a safeguard against u nderdosing. The incorporation of pharmacologic knowledge with virologic, im munologic, and behavioral considerations should result in improved clinical outcomes for children infected with HIV.