Population pharmacokinetics of peginterferon alfa-2b in pediatric patients with chronic hepatitis C |
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Authors: | C. Xu S. Gupta G. Krishna D. Cutler S. Wirth C. Galoppo M. Ciocca K. Kolz S. Noviello V. Sniukiene |
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Affiliation: | 1. Merck Research Laboratories, Kenilworth, NJ, USA 6. Sanofi US, 55 Corporate Drive, Mail Stop: 55B-405A, Bridgewater, NJ, 08807, USA 2. Cubist Pharmaceutical, Lexington, MA, USA 3. Children’s Hospital, HELIOS Klinikum Wuppertal, Witten-Herdecke University, Wuppertal, Germany 4. Hospital General de Ninos Dr. Ricardo Gutierrez, Buenos Aires, Argentina 5. Hospital Aleman, Buenos Aires, Argentina
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Abstract: | Purpose The aim of this study was to characterize the population pharmacokinetics of peginterferon (PEG-IFN) alfa-2b in pediatric patients with chronic hepatitis C and to identify covariates influencing PEG-IFN alfa-2b disposition. Methods Pharmacokinetic data from a multicenter open-label study of subcutaneously administered peginterferon alfa-2b (60 μg/m2/wk) plus oral ribavirin (15 mg/kg/day) in patients with chronic hepatitis C aged 3–17 years old was used to develop a population pharmacokinetic nonlinear mixed-effects model. Results The final population pharmacokinetic analysis was conducted with the pooled data from 107 pediatric patients. A one-compartment model with first-order absorption, first-order elimination, exponential inter-individual variability on clearance, and a combination additive and proportional residual error model adequately described the PEG-IFN alfa-2b pharmacokinetic profile. Age (apparent clearance and apparent volume of distribution) and sex (apparent clearance) were significant covariates. The mean body surface area normalized apparent clearance of PEG-IFN alfa-2b was 0.56 L/h/m2, and was similar when evaluated across the pediatric age groups. Conclusion The final population model suggests age-dependent increases in clearance and volume of distribution of PEG-IFN alfa-2b in pediatric patients with chronic hepatitis C. The apparent clearance normalized to body surface area was similar across pediatric age groups, supporting the use of body size–adjusted dosing in pediatric subjects. |
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