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Antimicrobial Agents and Chemotherapy, March 2001, p. 701-705, Vol. 45, No. 3
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.3.701-705.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Pharmacokinetics of the Protease Inhibitor Indinavir in Human Immunodeficiency Virus Type 1-Infected Children

David M. Burger,1,* Annemarie M. C. van Rossum,2 Patricia W. H. Hugen,1 Marja H. Suur,2 Nico G. Hartwig,2 Sibyl P. M. Geelen,3 Henriette J. Scherpbier,4 Richard M. W. Hoetelmans,5 Arnold G. Vulto,6 and Ronald de Groot2 for The Dutch Study Group For Children With Hiv-1 Infection

Department of Clinical Pharmacy, University Medical Centre Nijmegen, Nijmegen,1 Department of Pediatrics,2 and Department of Pharmacy,6 Sophia's Children Hospital/Erasmus University Medical Centre, Rotterdam, Department of Pediatrics, Wilhelmina Children's Hospital, Utrecht,3 and Department of Pediatrics, Emma Children's Hospital/Academical Medical Centre,4 and Department of Pharmacy, Slotervaart Hospital,5 Amsterdam, The Netherlands

Received 18 October 1999/Returned for modification 11 April 2000/Accepted 22 November 2000

The objective of this study was to evaluate the pharmacokinetics of indinavir in human immunodeficiency virus-infected children as part of a prospective, open, uncontrolled, multicenter study in The Netherlands. Human immunodeficiency virus type 1-infected children were monitored over 6 months of treatment with zidovudine (120 mg/m2 every 8 h [q8h]), lamivudine (4 mg/kg of body weight q12h), and indinavir (33mg/kg of metabolic weight [MW] q8h). Four weeks after the start of treatment, the steady-state pharmacokinetics of indinavir were determined by high-pressure liquid chromatography. If patients had an indinavir area under the concentration-time curve (AUC) of below 10 or above 30 mg/liter · h, a dose increase or a dose reduction was made and pharmacokinetic measurements were repeated 4 weeks later. Nineteen patients started with the dose of 33 mg/kg of MW q8h. The median AUC (range) was 10.5 (2.8 to 51.0) mg/liter · h. The median AUC (range) in 17 children treated with 50 mg/kg of MW q8h was 20.6 (4.1 to 38.7) mg/liter · h. Finally, five patients had a dose increase to 67 mg/kg of MW q8h, resulting in a median AUC (range) of 36.6 (27.2 to 80.0) mg/liter · h. After 6 months of treatment, there were 11 children with an AUC of below 20 mg/liter · h, of whom 5 (45%) had a detectable viral load, while this was the case in none of the 11 children with an AUC of higher than 20 mg/liter · h. We conclude that the optimal dose of indinavir in children to obtain drug exposure similar to that observed in adult patients is 50 mg/kg of MW q8h, which approximates 600 mg/m2 q8h. It would even be better to adjust the indinavir dose based on an AUC of greater than 20 mg/liter · h.

* Corresponding author. Mailing address: Department of Clinical Pharmacy, 533 KF University Medical Centre Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Phone: 3124 3616405. Fax: 3124 3540331. E-mail: D.Burger{at}klinfarm.azn.nl.

Antimicrobial Agents and Chemotherapy, March 2001, p. 701-705, Vol. 45, No. 3
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.3.701-705.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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