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

  • Pharmacokinetics and Disposition
  • Published:
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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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Acknowledgments

Writing assistance was provided by T. Ibbotson, PhD of ApotheCom. This assistance was funded by Schering-Plough Corporation, now Merck & Co., Inc., Whitehouse Station, N.J., U.S.A.

These data were presented at the 37th Annual Meeting of the American College of Clinical Pharmacology, September 14-16, 2008, Philadelphia, PA.

Financial disclosures

C Xu: clinical research support and stock ownership (Merck); G Krishna: stock ownership (Merck); D Cutler: stock ownership (Merck); K Kolz: stock ownership (Merck); S Noviello: former employee and consultant of Schering-Plough, now Merck; and stock ownership (Merck); current employee of Bristol-Myers Squibb; and stock ownership (Bristol-Myers Squibb); V Sniukiene: clinical research support and former employee (Schering-Plough, now Merck); S Gupta, S Wirth, C Galoppo, and M Ciocca,: nothing to disclose.

Statement of funding

The study discussed in this manuscript was funded by Schering-Plough Corporation, now Merck & Co., Inc.

Author information

Authors and Affiliations

  1. Merck Research Laboratories, Kenilworth, NJ, USA

    C. Xu, S. Gupta, D. Cutler, K. Kolz, S. Noviello & V. Sniukiene

  2. Cubist Pharmaceutical, Lexington, MA, USA

    G. Krishna

  3. Children’s Hospital, HELIOS Klinikum Wuppertal, Witten-Herdecke University, Wuppertal, Germany

    S. Wirth

  4. Hospital General de Ninos Dr. Ricardo Gutierrez, Buenos Aires, Argentina

    C. Galoppo

  5. Hospital Aleman, Buenos Aires, Argentina

    M. Ciocca

  6. Sanofi US, 55 Corporate Drive, Mail Stop: 55B-405A, Bridgewater, NJ, 08807, USA

    C. Xu

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  1. C. Xu
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Corresponding author

Correspondence to C. Xu.

Additional information

C. Xu, S. Gupta, G. Krishna and S. Noviello are former employees of Merck Sharp & Dohme Corp.

This study is registered at www.clinicaltrials.gov identifier NCT00104052

Electronic supplementary material

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Supplemental Figure 1

Correlation of demographic variables, serum creatinine, and creatinine clearance. Body weight (WT), height (HT), serum creatinine (SCr), estimated creatinine clearance (CrCl) by Schwartz formula. (DOCX 160 kb)

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Xu, C., Gupta, S., Krishna, G. et al. Population pharmacokinetics of peginterferon alfa-2b in pediatric patients with chronic hepatitis C. Eur J Clin Pharmacol 69, 2045–2054 (2013). https://doi.org/10.1007/s00228-013-1574-9

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  • DOI: https://doi.org/10.1007/s00228-013-1574-9

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