Population pharmacokinetics of peginterferon alfa-2b in pediatric patients with chronic hepatitis C.

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/m(2)/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/m(2), 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.

• Authors: C Xu, S Gupta, G Krishna, D Cutler, S Wirth, C Galoppo, M Ciocca, K Kolz, S Noviello, V Sniukiene
• Journal: European journal of clinical pharmacology (Eur J Clin Pharmacol) Vol. 69 Issue 12 Pg. 2045-54 (Dec 2013) ISSN: 1432-1041 [Electronic] Germany
• PMID: 23975236 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase III, Journal Article, Multicenter Study)

Chemical References

• Antiviral Agents
• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• Polyethylene Glycols
• peginterferon alfa-2b

Topics

• Adolescent
• Age Factors
• Antiviral Agents (pharmacokinetics)
• Child
• Child, Preschool
• Female
• Hepatitis C, Chronic (metabolism)
• Humans
• Interferon alpha-2
• Interferon-alpha (pharmacokinetics)
• Male
• Models, Biological
• Polyethylene Glycols (pharmacokinetics)
• Recombinant Proteins (pharmacokinetics)
• Reproducibility of Results