title: Assessment of hemoglobin responsiveness to epoetin alfa in patients on hemodialysis using a population pharmacokinetic pharmacodynamic model.
abstract: A population pharmacokinetic pharmacodynamic (PK/PD) model describing the effect of epoetin alfa on hemoglobin (Hb) response in hemodialysis patients was developed. Epoetin alfa pharmacokinetics was described using a linear 2-compartment model. PK parameter estimates were similar to previously reported values. A maturation-structured cytokinetic model consisting of 5 compartments linked in a catenary fashion by first-order cell transfer rates following a zero-order input process described the Hb time course. The PD model described 2 subpopulations, one whose Hb response reflected epoetin alfa dosing and a second whose response was unrelated to epoetin alfa dosing. Parameter estimates from the PK/PD model were physiologically reasonable and consistent with published reports. Numerical and visual predictive checks using data from 2 studies were performed. The PK and PD of epoetin alfa were well described by the model.
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Liviawati
authors.initials: L
authors.lastname: Wu
authors.affiliation: Projections Research Inc., Phoenixville, PA, USA.
authors.forename: Diane R
authors.initials: DR
authors.lastname: Mould
authors.affiliation: Janssen Research & Development, Janssen Pharmaceutica, Beerse, Belgium.
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Perez Ruixo
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Sameer
authors.initials: S
authors.lastname: Doshi
mesh_terms: D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D000068817:Epoetin Alfa / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006397:Hematinics / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*
chemical_list: D006397:Hematinics; D006454:Hemoglobins; D000068817:Epoetin Alfa
keywords: chronic kidney disease; epoetin alfa; erythropoietin; pharmacokinetic pharmacodynamic model