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Research ArticleMETABOLISM, TRANSPORT, AND PHARMACOGENOMICS

Erythropoietic Response to Endogenous Erythropoietin in Premature Very Low Birth Weight Infants

Kevin J. Freise, John A. Widness and Peter Veng-Pedersen
Journal of Pharmacology and Experimental Therapeutics January 2010, 332 (1) 229-237; DOI: https://doi.org/10.1124/jpet.109.159905
Kevin J. Freise
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Peter Veng-Pedersen
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Abstract

Despite the common occurrence of anemia in very low birth weight (VLBW) infants, the erythropoiesis and Hb production rates and their relationship to plasma erythropoietin (EPO) concentrations remain unknown in these subjects. To determine these quantities, all blood removed by phlebotomy and administered by red blood cell (RBC) transfusion over the first 30 days of life was recorded in 14 ventilated VLBW infants born at 24 to 28 weeks of gestation. Discarded blood from frequent clinically ordered laboratory blood samples was used to construct plasma EPO, Hb, and RBC concentration-time profiles for each infant. A pharmacodynamic Hb mass balance model that accounted for the dynamic hematological conditions experienced by these infants was simultaneously fitted to the plasma EPO, Hb, and RBC concentrations from each individual subject, while accounting for subject growth. Based on the model estimates, an average of 4.69 g of Hb was produced over the first 30 days of life, compared with 5.97 g removed by phlebotomies and 12.3 g administered by transfusions. These high transfusion amounts were consistent with a relatively short RBC life span and rapidly expanding blood volume with infant growth. The estimated mean body weight-scaled Hb production rate dropped nearly 3-fold after birth to 0.144 g/day·(kg)3/4. Although only estimated in a subset of the subjects, the mean plasma EPO EC50 of 28.5 mU/ml and maximal Hb production rate (Emax) indicated that a severalfold increase in Hb production rate could be achieved with only a modest increase in plasma EPO concentrations.

Footnotes

  • This work was supported in part by the National Institutes of Health U.S. Public Health Service [Grant 2 P01-HL046925-11A1]; The University of Iowa Presidential Graduate Fellowship; and the American Federation of Pharmaceutical Education Predoctoral Fellowship.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.109.159905

  • ↵Embedded Image The online version of this article (available at http://jpet.aspetjournals.org) contains supplemental material.

  • ABBREVIATIONS:

    EPO
    erythropoietin
    rHuEPO
    recombinant human erythropoietin
    PD
    pharmacodynamic
    Hct
    hematocrit
    MSE%
    mean percent standard error
    AIC
    Akaike's information criterion
    VLBW
    very low birth weight
    RBC
    red blood cell.

    • Received August 3, 2009.
    • Accepted October 6, 2009.
  • © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 332 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 332, Issue 1
1 Jan 2010
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Research ArticleMETABOLISM, TRANSPORT, AND PHARMACOGENOMICS

Erythropoietic Response to Endogenous Erythropoietin in Premature Very Low Birth Weight Infants

Kevin J. Freise, John A. Widness and Peter Veng-Pedersen
Journal of Pharmacology and Experimental Therapeutics January 1, 2010, 332 (1) 229-237; DOI: https://doi.org/10.1124/jpet.109.159905

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Research ArticleMETABOLISM, TRANSPORT, AND PHARMACOGENOMICS

Erythropoietic Response to Endogenous Erythropoietin in Premature Very Low Birth Weight Infants

Kevin J. Freise, John A. Widness and Peter Veng-Pedersen
Journal of Pharmacology and Experimental Therapeutics January 1, 2010, 332 (1) 229-237; DOI: https://doi.org/10.1124/jpet.109.159905
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