title: Pharmacokinetics of the protease inhibitor indinavir in human immunodeficiency virus type 1-infected children.
abstract: 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/m(2) 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/m(2) q8h. It would even be better to adjust the indinavir dose based on an AUC of greater than 20 mg/liter. h.
authors.affiliation: Department of Clinical Pharmacy, University Medical Centre Nijmegen, Nijmegen, The Netherlands. D.Burger@klinfarm.azn.nl
authors.forename: D M
authors.initials: DM
authors.lastname: Burger
authors.forename: A M
authors.initials: AM
authors.lastname: van Rossum
authors.forename: P W
authors.initials: PW
authors.lastname: Hugen
authors.forename: M H
authors.initials: MH
authors.lastname: Suur
authors.forename: N G
authors.initials: NG
authors.lastname: Hartwig
authors.forename: S P
authors.initials: SP
authors.lastname: Geelen
authors.forename: H J
authors.initials: HJ
authors.lastname: Scherpbier
authors.forename: R M
authors.initials: RM
authors.lastname: Hoetelmans
authors.forename: A G
authors.initials: AG
authors.lastname: Vulto
authors.forename: R
authors.initials: R
authors.lastname: de Groot
mesh_terms: D000293:Adolescent; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D019469:Indinavir / Q000097:blood / Q000493:pharmacokinetics*; D007223:Infant; D008297:Male; D011446:Prospective Studies
chemical_list: D017320:HIV Protease Inhibitors; D019469:Indinavir