Population pharmacokinetic analysis of raltegravir pediatric formulations in HIV-infected children 4 weeks to 18 years of age

Journal of Clinical Pharmacology
Matthew L RizkEdward P Acosta

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 incorpor...Continue Reading

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Citations

Jul 19, 2016·Advances in Pediatrics·Laura A WangDaniel Gonzalez
Nov 4, 2017·Expert Review of Clinical Pharmacology·Louise Kuhn, Stephanie Shiau
Jul 12, 2018·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Elaine J AbramsPim Brouwers
Jun 20, 2019·CPT: Pharmacometrics & Systems Pharmacology·Jos LommerseAnne Chain
Oct 29, 2019·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Diana F ClarkeUNKNOWN International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1110 Study Team
Apr 23, 2019·Therapeutic Drug Monitoring·Hylke WaalewijnUNKNOWN Pediatric Antiretroviral Working Group (PAWG)
Jul 30, 2020·Journal of the International AIDS Society·Gabriela PattenUNKNOWN IeDEA
Jan 9, 2020·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Diana F ClarkeUNKNOWN IMPAACT P1110 Protocol Team
Dec 29, 2020·CPT: Pharmacometrics & Systems Pharmacology·Vera E BukkemsElin M Svensson

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