Population Pharmacokinetics of Darbepoetin in Infants Following Single Intravenous and Subcutaneous Dosing

Guohua An; Robin K Ohls; Robert D Christensen; John A Widness; Donald M Mock; Peter Veng-Pedersen

doi:10.1016/j.xphs.2017.02.001

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Population Pharmacokinetics of Darbepoetin in Infants Following Single Intravenous and Subcutaneous Dosing

Journal article

Peer reviewed

Population Pharmacokinetics of Darbepoetin in Infants Following Single Intravenous and Subcutaneous Dosing

Guohua An, Robin K Ohls, Robert D Christensen, John A Widness, Donald M Mock and Peter Veng-Pedersen

Journal of pharmaceutical sciences, Vol.106(6), pp.1644-1649

06/2017

DOI: 10.1016/j.xphs.2017.02.001

PMCID: PMC6190690

PMID: 28189627

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https://www.ncbi.nlm.nih.gov/pmc/articles/6190690View

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Abstract

Darbepoetin alfa (Darbe) is a hyperglycosylated analogue of recombinant human erythropoietin (Epo). The aim of this study was to develop a population pharmacokinetic model for Darbe following intravenous (i.v.) and subcutaneous (s.c.) administration to infants. Data from 2 infant clinical studies (a single i.v. dose study following a 4 μg/kg dose of Darbe, and a single s.c. dose study following 1 μg/kg or 4 μg/kg dose of Darbe) were combined and analyzed simultaneously using nonlinear mixed-effect modeling approach. Darbe population pharmacokinetics was well described by a 2-compartment model with first-order elimination. The covariate analysis identified significant impact of gender on clearance and bodyweight on volume of distribution. The clearance of Darbe was estimated to be 0.050 L/h/kg in male infants and 0.031 L/h/kg in female infants. The predicted population mean value of Vp is 0.84 L/kg, which is associated with the subject's bodyweight (p < 0.05). Following s.c. administration, the estimated absorption rate (i.e., ka) of Darbe was 0.062 L/h. The model provides a suitable starting point for the development of further pharmacokinetic-pharmacodynamic models in infants in a variety of disease settings. Because the covariate-pharmacokinetic parameter relationships were identified in only 22 infants, further investigation with larger sample size is warranted.

Humans

Child, Preschool

Half-Life

Infant

Male

Administration, Cutaneous

Darbepoetin alfa - administration & dosage

Darbepoetin alfa - pharmacokinetics

Hematinics - administration & dosage

Administration, Intravenous

Models, Biological

Female

Hematinics - pharmacokinetics

Details

Title: Subtitle: Population Pharmacokinetics of Darbepoetin in Infants Following Single Intravenous and Subcutaneous Dosing
Creators: Guohua An - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242. Electronic address: Guohua-an@uiowa.edu
Robin K Ohls - Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico 87131
Robert D Christensen - Department of Pediatrics, University of Utah, Salt Lake City, Utah 84132
John A Widness - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242
Donald M Mock - Departments of Biochemistry and Molecular Biology and Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
Peter Veng-Pedersen - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242
Resource Type: Journal article
Publication Details: Journal of pharmaceutical sciences, Vol.106(6), pp.1644-1649
DOI: 10.1016/j.xphs.2017.02.001
PMID: 28189627
PMCID: PMC6190690
NLM abbreviation: J Pharm Sci
ISSN: 0022-3549
eISSN: 1520-6017
Publisher: United States
Grant note: P01 HL046925 / NHLBI NIH HHS
Language: English
Date published: 06/2017
Academic Unit: Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984065690702771

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