Document Detail


Population pharmacodynamic analysis of erythropoiesis in preterm infants for determining the anemia treatment potential of erythropoietin.
MedLine Citation:
PMID:  23485870     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A population pharmacokinetics/pharmacodynamic (PK/PD) model was developed to describe changes in erythropoiesis as a function of plasma erythropoietin (EPO) concentration over the first 30 days of life in preterm infants who developed severe anemia requiring red blood cell (RBC) transfusion. Several covariates were tested as possible factors influencing the responsiveness to EPO. Discarded blood samples in 27 ventilated preterm infants born at 24-29 wk of gestation were used to construct plasma EPO, hemoglobin (Hb), and RBC concentration-time profiles. The amount of Hb removed for laboratory testing and that transfused throughout the study period were recorded. A population PK/PD model accounting for the dynamic Hb changes experienced by these infants was simultaneously fitted to plasma EPO, Hb, and RBC concentrations. A covariate analysis suggested that the erythropoietic efficacy of EPO is increased for preterm infants at later gestational ages. The PD analysis showed a sevenfold difference in maximum Hb production rate dependent on gestational age and indicated that preterm infants, when stimulated by EPO, have the capacity to produce additional Hb that may result in a decrease in RBC transfusions. The present model has utility in clinical trial simulations investigating the treatment potential of erythropoietic stimulating agents in the treatment of anemia of prematurity.
Authors:
Mohammad I Saleh; Demet Nalbant; John A Widness; Peter Veng-Pedersen
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-03-13
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  304     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-06-20     Completed Date:  2013-08-26     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R772-81     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Algorithms
Anemia / diagnosis*,  drug therapy*
Blood Volume / physiology
Data Interpretation, Statistical
Erythrocyte Aging / physiology
Erythropoiesis / physiology*
Erythropoietin / pharmacokinetics*,  therapeutic use*
Female
Gestational Age
Hemoglobins / metabolism
Humans
Infant, Newborn
Infant, Premature / physiology*
Models, Statistical
Phlebotomy
Plasma Substitutes / pharmacology
Population
Pregnancy
Recombinant Proteins / pharmacokinetics,  therapeutic use
Grant Support
ID/Acronym/Agency:
2 P01HL046925/HL/NHLBI NIH HHS; P01 HL046925/HL/NHLBI NIH HHS; UL1 RR024979/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Hemoglobins; 0/Plasma Substitutes; 0/Recombinant Proteins; 11096-26-7/Erythropoietin; 113427-24-0/epoetin alfa
Comments/Corrections

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