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

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 o...

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Publicado en:European Journal of Clinical Pharmacology Vol. 69; no. 12; pp. 2045 - 2055
Autores principales: Xu, C., Gupta, S., Krishna, G., Cutler, D., Wirth, S., Galoppo, C., Ciocca, M., Kolz, K., Noviello, S., Sniukiene, V.
Formato: equations & formulas research tables/charts Journal Article
Publicado: Springer Nature Dec2013
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Dec2013
      vid: 69
      iid: 12
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00228-013-1574-9
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        atl: Population pharmacokinetics of peginterferon alfa-2b in pediatric patients with chronic hepatitis C.
      aug:
        au:
          Xu, C.
          Gupta, S.
          Krishna, G.
          Cutler, D.
          Wirth, S.
          Galoppo, C.
          Ciocca, M.
          Kolz, K.
          Noviello, S.
          Sniukiene, V.
        affil: Merck Research Laboratories, Kenilworth, NJ, USA; Sanofi US, 55 Corporate Drive, Mail Stop: 55B-405A, Bridgewater, NJ, 08807, USA
      sug:
        subj:
          Interferons Pharmacokinetics
          Hepatitis C, Chronic Drug Therapy
          Interferons Administration and Dosage
          Ribavirin Administration and Dosage
          Human
          Multicenter Studies
          Child, Preschool
          Child
          Adolescence
          Models, Statistical
          Americas
          Europe
          Data Analysis Software
          Descriptive Statistics
          Confidence Intervals
          Male
          Female
          Funding Source
          Child, Preschool: 2-5 years
          Child: 6-12 years
          Adolescent: 13-18 years
          Male
          Female
      ab: 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.
      pubtype: Academic Journal
      doctype:
        equations & formulas
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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