title: Multidose optimization simulation of erythropoietin treatment in preterm infants.
abstract: BACKGROUND
  Preterm infants commonly develop anemia requiring red blood cell transfusions (RBCTx). Although an alternative therapy is recombinant human erythropoietin (Epo), it is not widely employed. To provide a rigorous scientific basis supporting the latter approach, a model-based simulation analysis of endogenous erythropoiesis was developed.
  
  
  RESULTS
  The pharmacodynamic/pharmacokinetic (PK/PD) model identified an optimal Epo dosing algorithm in preterm infants that demonstrated maximal efficacy when Epo was dosed frequently during the early weeks of life (when phlebotomy loss is greatest). Model-based simulations employing optimized Epo dosing predicted that 13 of the 27 (46%) infants would avoid RBCTx ("good responders"). Importantly, simulation results identified five subject-specific covariate factors predictive of good Epo response.
  
  
  CONCLUSIONS
  This simulation study provides a basis for possibly eliminating RBCTx in infants who can be selected for optimized Epo therapy.
  
  
  METHODS
  Epo PD hemoglobin production parameters were determined in 27 preterm infants studied intensively during the first 28 d of life. Model-derived Epo PD parameters were combined with PK parameters derived from the literature to simulate an optimized intravenous Epo bolus dosing schedule. The goal of this simulated optimized schedule was to eliminate RBCTx, as prescribed per current guidelines, in as many preterm infants as possible.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Rosebraugh
authors.forename: John A
authors.initials: JA
authors.lastname: Widness
authors.forename: Peter
authors.initials: P
authors.lastname: Veng-Pedersen
mesh_terms: D000465:Algorithms; D019540:Area Under Curve; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage* / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D015931:Intensive Care, Neonatal; D015233:Models, Statistical; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004921:Erythropoietin