title: Pharmacokinetics of darbepoetin alfa in pediatric patients with chronic kidney disease.
abstract: Darbepoetin alfa is a novel erythropoiesis-stimulating protein with a two- to threefold longer half-life than recombinant human erythropoietin (epoetin) in adult patients with chronic kidney disease (CKD). This randomized, open-label, crossover study was conducted to determine the pharmacokinetic profile of darbepoetin alfa in pediatric patients with CKD. Twelve patients 3-16 years of age with CKD were randomized and received a single 0.5 micro g/kg dose of darbepoetin alfa administered intravenously (IV) or subcutaneously (SC). After a 14- to 16-day washout period, patients received an identical dose of darbepoetin alfa by the alternate route. After IV administration, the mean clearance of darbepoetin alfa was 2.3 ml/h per kg, with a mean terminal half-life of 22.1 h. After SC administration, absorption was rate limiting, with a mean terminal half-life of 42.8 h and a mean bioavailability of 54%. Comparison of these results with those from a previous study of darbepoetin alfa in adult patients indicated that the disposition of darbepoetin alfa administered IV or SC is similar in adult and pediatric patients, although absorption may be slightly more rapid in pediatric patients after SC dosing. The mean terminal half-life of darbepoetin alfa in this study was approximately two- to fourfold longer than that previously reported for epoetin in pediatric patients.
authors.affiliation: Division of Nephrology, Children's Hospital Los Angeles, 4650 Sunset Boulevard, Los Angeles, CA 90027, USA. glerner@chla.usc.edu
authors.forename: Gary
authors.initials: G
authors.lastname: Lerner
authors.forename: Arundhati S
authors.initials: AS
authors.lastname: Kale
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Warady
authors.forename: Kathy
authors.initials: K
authors.lastname: Jabs
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Bunchman
authors.forename: Anne
authors.initials: A
authors.lastname: Heatherington
authors.forename: Kurt
authors.initials: K
authors.lastname: Olson
authors.forename: Louise
authors.initials: L
authors.lastname: Messer-Mann
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Maroni
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D000068256:Darbepoetin alfa; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D006435:Renal Dialysis
chemical_list: D004921:Erythropoietin; D000068256:Darbepoetin alfa