title: Population pharmacokinetic analysis of raltegravir pediatric formulations in HIV-infected children 4 weeks to 18 years of age.
abstract: P1066 is an open-label study of raltegravir in HIV positive youth, ages 4 weeks-18 years. Here we summarize P1066 pharmacokinetic (PK) data and a population PK model for the pediatric chewable tablet and oral granules. Raltegravir PK parameters were calculated using noncompartmental analysis. A 2-compartment model was developed using data from P1066 and an adult study of the pediatric formulations. Interindividual variability was described by an exponential error model, and residual variability was captured by an additive/proportional error model. Twelve-hour concentrations (C12h ) were calculated from the model-derived elimination rate constant and 8-hour observed concentration. Simulated steady-state concentrations were analyzed by noncompartmental analysis. Target area under the curve (AUC0-12h ) and C12h were achieved in each cohort. For the pediatric formulations, geometric mean AUC0-12h values were 18.0-22.6 μM-hr across cohorts, and C12h values were 71-130 nM, with lower coefficients of variation versus the film-coated tablet. A 2-compartment model with first-order absorption adequately described raltegravir plasma PK in pediatric and adult patients. Weight was a covariate on clearance and central volume and was incorporated using allometric scaling. Raltegravir chewable tablets and oral granules exhibited PK parameters consistent with those from prior adult studies and older children in P1066, as well as lower variability than the film-coated tablet.
authors.affiliation: Merck Sharp & Dohme Corp., Kenilworth, NJ, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Rizk
authors.affiliation: Merck Sharp & Dohme Corp., Kenilworth, NJ, USA.
authors.forename: Lihong
authors.initials: L
authors.lastname: Du
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Chantelle
authors.initials: C
authors.lastname: Bennetto-Hood
authors.affiliation: Merck Sharp & Dohme Corp., Kenilworth, NJ, USA.
authors.forename: Larissa
authors.initials: L
authors.lastname: Wenning
authors.affiliation: Merck Sharp & Dohme Corp., Kenilworth, NJ, USA.
authors.forename: Hedy
authors.initials: H
authors.lastname: Teppler
authors.affiliation: Merck Sharp & Dohme Corp., Kenilworth, NJ, USA.
authors.forename: Brenda
authors.initials: B
authors.lastname: Homony
authors.affiliation: Frontier Science Inc., Buffalo, NY, USA.
authors.forename: Bobbie
authors.initials: B
authors.lastname: Graham
authors.affiliation: Frontier Science Inc., Buffalo, NY, USA.
authors.forename: Carrie
authors.initials: C
authors.lastname: Fry
authors.affiliation: State University of New York, Department of Pediatrics, Stony Brook, NY, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Nachman
authors.affiliation: Albert Einstein College of Medicine, Jacobi Medical Center, Bronx, NY, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wiznia
authors.affiliation: National Institute of Child Health and Human Development, Bethesda, MD, USA.|Division of AIDS, NIAID, NIH, Bethesda, MD, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Worrell
authors.affiliation: Division of AIDS, NIAID, NIH, Bethesda, MD, USA.
authors.forename: Betsy
authors.initials: B
authors.lastname: Smith
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Acosta
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008954:Models, Biological; D000068898:Raltegravir Potassium / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013607:Tablets
chemical_list: D019380:Anti-HIV Agents; D013607:Tablets; D000068898:Raltegravir Potassium
keywords: HIV/AIDS; IMPAACT study; pediatrics; pharmacokinetics; raltegravir