Document Detail

Multidose optimization simulation of erythropoietin treatment in preterm infants.
MedLine Citation:
PMID:  22391632     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: 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.
DISCUSSION: 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.
Matthew R Rosebraugh; John A Widness; Peter Veng-Pedersen
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-02-15
Journal Detail:
Title:  Pediatric research     Volume:  71     ISSN:  1530-0447     ISO Abbreviation:  Pediatr. Res.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-06     Completed Date:  2012-07-16     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  332-7     Citation Subset:  IM    
Department of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, USA.
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MeSH Terms
Area Under Curve
Computer Simulation
Dose-Response Relationship, Drug
Drug Administration Schedule*
Erythropoietin / administration & dosage*,  blood
Infant, Newborn
Infant, Premature
Intensive Care, Neonatal
Models, Statistical
Time Factors
Treatment Outcome
Grant Support
Reg. No./Substance:

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