Journal article
A Mechanism-Based Population Pharmacokinetics Model of Erythropoietin in Premature Infants and Healthy Adults Following Multiple Intravenous Doses
Journal of clinical pharmacology, Vol.59(6), pp.835-846
06/01/2019
DOI: 10.1002/jcph.1368
PMCID: PMC7485325
PMID: 30618050
Abstract
The objective of the current study was to develop a population pharmacokinetics (PK) model for erythropoietin (Epo) in premature infants and healthy adults to characterize the variation in PK, and to study the differences in Epo PK in these 2 populations. Thirteen very low-birth-weight premature infants (<1500 g at birth), and 10 healthy adults received up to 4 intravenous doses of Epo that ranged from 10 to 500 U/kg. The final model had a target-mediated saturable, nonlinear, elimination pathway that incorporated the mechanism of Epo binding to its receptors along with a parallel linear, central elimination pathway. Epo clearance was found to be significantly higher in preterm infants compared to adults. Epo clearance via the nonlinear pathway was found to be much higher in infants; they had an Epo receptor capacity of 133 pM vs 86.6 pM in adults, which is most likely due to the higher erythroid progenitor cell mass per kilogram of body weight in infants. The parallel linear elimination was found to be more dominant in adults, reaching 91% of the total clearance with a 500-U/kg dose compared to just 6.1% of the total clearance following the same dose in preterm infants. Thus, this mechanism-based population PK model revealed that receptor-based nonlinear elimination is the dominant Epo elimination pathway in premature infants, and parallel linear elimination is dominant in adults.
Details
- Title: Subtitle
- A Mechanism-Based Population Pharmacokinetics Model of Erythropoietin in Premature Infants and Healthy Adults Following Multiple Intravenous Doses
- Creators
- Ronilda D'Cunha - University of IowaJohn A. Widness - University of IowaXiaoyu Yan - Chinese University of Hong KongRobert L. Schmidt - University of IowaPeter Veng-Pedersen - University of IowaGuohua An - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of clinical pharmacology, Vol.59(6), pp.835-846
- DOI
- 10.1002/jcph.1368
- PMID
- 30618050
- PMCID
- PMC7485325
- NLM abbreviation
- J Clin Pharmacol
- ISSN
- 0091-2700
- eISSN
- 1552-4604
- Publisher
- Wiley
- Number of pages
- 12
- Grant note
- Robert Wood Johnson Pharmaceutical Research Institute HL-46925; P01 HL046925; RR-000159 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Children's Miracle Network Telethon
- Language
- English
- Date published
- 06/01/2019
- Academic Unit
- Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984365885202771
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