P1066 is an open-label study of raltegravir in HIV+ 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 non-compartmental analysis. A two-compartment model was developed using data from P1066 and an adult study of the pediatric formulations. Inter-individual variability was described by an exponential error model, and residual variability was captured by an additive/proportional error model. Twelve-hour concentrations (C12hr ) were calculated from the model-derived elimination rate constant and 8-hour observed concentration. Simulated steady-state concentrations were analyzed by non-compartmental analysis. Target area-under-the-curve (AUC0-12hr ) and C12hr were achieved in each cohort. For the pediatric formulations, geometric mean AUC0-12hr values were 18.0-22.6 µM*hr across cohorts, and C12hr values were 71-130 nM, with lower coefficients of variation vs the film-coated tablet. A two-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 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. This article is protected by copyright. All rights reserved.

 

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