title: Population pharmacokinetics of peginterferon alfa-2b in pediatric patients with chronic hepatitis C.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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: Merck Research Laboratories, Kenilworth, NJ, USA, rongxuus@yahoo.com.
authors: C
authors: C
authors: Xu
authors: S
authors: S
authors: Gupta
authors: G
authors: G
authors: Krishna
authors: D
authors: D
authors: Cutler
authors: S
authors: S
authors: Wirth
authors: C
authors: C
authors: Galoppo
authors: M
authors: M
authors: Ciocca
authors: K
authors: K
authors: Kolz
authors: S
authors: S
authors: Noviello
authors: V
authors: V
authors: Sniukiene
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D019698:Hepatitis C, Chronic / Q000378:metabolism*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D011092:Polyethylene Glycols / Q000493:pharmacokinetics*; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D015203:Reproducibility of Results
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b
references: Pharm Res. 1998 Sep;15(9):1463-8
references: 9755901
references: Hepatology. 2005 Nov;42(5):1010-8
references: 16250032
references: J Hepatol. 2006 Aug;45(2):204-13
references: 16780997
references: J Hepatol. 2010 Apr;52(4):501-7
references: 20189674
references: Ann Intern Med. 2004 Mar 2;140(5):346-55
references: 14996676
references: Liver Int. 2009 Jan;29 Suppl 1:74-81
references: 19207969
references: Clin Pharmacol Ther. 2007 Jul;82(1):17-20
references: 17571070
references: N Engl J Med. 2002 Sep 26;347(13):975-82
references: 12324553
references: Gastroenterology. 2008 Jun;134(7):1900-7
references: 18439604
references: Hepatology. 2008 Mar;47(3):836-43
references: 18167062
references: J Pediatr Gastroenterol Nutr. 2006 Oct;43(4):499-505
references: 17033526
references: Pediatr Blood Cancer. 2010 Jul 15;55(1):108-12
references: 20127849
references: J Pharmacokinet Biopharm. 1992 Oct;20(5):511-28
references: 1287200
references: Lancet. 2001 Sep 22;358(9286):958-65
references: 11583749
references: Antivir Chem Chemother. 2004 Nov;15(6):287-97
references: 15646642
references: Clin Pharmacol Ther. 2001 Jun;69(6):407-21
references: 11406738
references: Pediatrics. 1976 Aug;58(2):259-63
references: 951142
references: Hepatology. 2005 May;41(5):1013-8
references: 15793840
references: N Engl J Med. 2009 Aug 6;361(6):580-93
references: 19625712
references: Gastroenterology. 2011 Feb;140(2):450-458.e1
references: 21036173
references: Cancer Chemother Pharmacol. 2010 Mar;65(4):671-7
references: 19621225
references: Clin Pharmacol Ther. 2000 Nov;68(5):556-67
references: 11103758