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Antimicrobial Agents and Chemotherapy, April 2000, p. 1029-1034, Vol. 44, No. 4
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Pharmacologic Characteristics of Indinavir, Didanosine, and Stavudine in Human Immunodeficiency Virus-Infected Children Receiving Combination Therapy

Courtney V. Fletcher,1,* Richard C. Brundage,1 Rory P. Remmel,1 Linda M. Page,1 Dennis Weller,1 Nancy R. Calles,2 Cara Simon,2 and Mark W. Kline2

University of Minnesota Health Sciences Center, Minneapolis, Minnesota,1 Baylor College of Medicine, and Texas Children's Hospital, Houston, Texas2

Received 11 June 1999/Returned for modification 14 November 1999/Accepted 10 January 2000

The use of human immunodeficiency virus (HIV) protease inhibitors in children has lagged behind that in adults because of the lack of suitable pediatric formulations and information on safe and effective dosing regimens. This study was designed to obtain pharmacokinetic information on indinavir, administered to HIV-infected children also receiving therapy with two nucleoside agents, and to explore relationships between pharmacokinetic parameters and anti-HIV effect. Indinavir was initiated at a dose of 500 mg/m2 every 8 h. Plasma indinavir concentrations were measured every 4 weeks; the dose or dosing interval was adjusted to maintain trough concentrations of >= 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/m2; nine children received indinavir at 6-h intervals. Pharmacokinetic characteristics of indinavir (mean ± 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 baseline-to-week-24 change in HIV RNA level was related to indinavir trough concentration 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 underdosing. The incorporation of pharmacologic knowledge with virologic, immunologic, and behavioral considerations should result in improved clinical outcomes for children infected with HIV.

* Corresponding author. Mailing address: University of Minnesota, 7-151 Weaver-Densford Hall, 308 Harvard St., S.E., Minneapolis, MN 55455. Phone: (612) 624-6489. Fax: (612) 625-9931. E-mail: fletc001{at}tc.umn.edu.

Antimicrobial Agents and Chemotherapy, April 2000, p. 1029-1034, Vol. 44, No. 4
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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