Population Pharmacokinetics of Darbepoetin in Infants Following Single Intravenous and Subcutaneous Dosing

J Pharm Sci. 2017 Jun;106(6):1644-1649. doi: 10.1016/j.xphs.2017.02.001. Epub 2017 Feb 9.


Darbepoetin alfa (Darbe) is a hyperglycosylated analogue of recombinant human erythropoietin (Epo). The aim of this study was to develop a population pharmacokinetic model for Darbe following intravenous (i.v.) and subcutaneous (s.c.) administration to infants. Data from 2 infant clinical studies (a single i.v. dose study following a 4 μg/kg dose of Darbe, and a single s.c. dose study following 1 μg/kg or 4 μg/kg dose of Darbe) were combined and analyzed simultaneously using nonlinear mixed-effect modeling approach. Darbe population pharmacokinetics was well described by a 2-compartment model with first-order elimination. The covariate analysis identified significant impact of gender on clearance and bodyweight on volume of distribution. The clearance of Darbe was estimated to be 0.050 L/h/kg in male infants and 0.031 L/h/kg in female infants. The predicted population mean value of Vp is 0.84 L/kg, which is associated with the subject's bodyweight (p < 0.05). Following s.c. administration, the estimated absorption rate (i.e., ka) of Darbe was 0.062 L/h. The model provides a suitable starting point for the development of further pharmacokinetic-pharmacodynamic models in infants in a variety of disease settings. Because the covariate-pharmacokinetic parameter relationships were identified in only 22 infants, further investigation with larger sample size is warranted.

Keywords: clinical pharmacokinetics; clinical trials; pharmacokinetic/pharmacodynamic models; pharmacokinetics; population pharmacokinetics.

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Cutaneous
  • Administration, Intravenous
  • Child, Preschool
  • Darbepoetin alfa / administration & dosage*
  • Darbepoetin alfa / pharmacokinetics*
  • Female
  • Half-Life
  • Hematinics / administration & dosage*
  • Hematinics / pharmacokinetics*
  • Humans
  • Infant
  • Male
  • Models, Biological


  • Hematinics
  • Darbepoetin alfa