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Original Paper

Free Access

Pharmacokinetics of Protein C and Antithrombin in the Fetal Lamb: A Model to Predict Human Neonatal Replacement Dosing

Manco-Johnson M.J.a, b · Hacker M.R.a, d · Jacobson L.J.a, b · Hay, Jr. W.W.b, c

Author affiliations

aMountain States Regional Hemophilia and Thrombosis Center, bDepartment of Pediatrics, and cPerinatal Research Center, University of Colorado Denver, Aurora, Colo., and dDepartment of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass., USA

Corresponding Author

Marilyn J. Manco-Johnson

Mountain States Regional Hemophilia and Thrombosis Center

PO Box 6507, MS F416

Aurora, CO 80045-0507 (USA)

Tel. +1 303 724 0365, Fax +1 303 724 0947, E-Mail marilyn.manco-johnson@uchsc.edu

Related Articles for ""

Neonatology 2009;95:279–285

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Background: The preterm infant is at risk for consumptive coagulopathy and thrombosis due to late maturation of coagulation regulatory proteins. Replacement proteins are available, but neonatal pharmacokinetic data are lacking. Objective: The objective was to determine the pharmacokinetic properties of antithrombin (AT) and protein C (PC) in order to provide data for estimating doses in human infants. Methods: A catheterized ovine model was used to determine pharmacokinetic properties of AT and PC, including plasma recovery, volume of distribution (Vd), clearance (Cl) and half-life (t½), in the fetal lamb relative to the ewe. Results: AT studies showed statistically significant differences between ewes and fetuses in recovery (p < 0.0001), Vd (p = 0.0002) and Cl (p < 0.0001). The AT t½ was significantly shortened among fetuses (5.55 h, 95% CI: 4.01–7.08) compared to ewes (18.7 h, 95% CI: 11.6–25.8). PC recovery (p < 0.0001), Vd (p < 0.0001) and Cl (p = 0.004) differed significantly between ewes and singleton fetuses as did the t½: 3.86 h (95% CI: 3.35–4.36) and 11.9 h (95% CI: 10.9–12.9) in the singletons and ewes, respectively. All PC parameters were significantly different for twins compared to ewes. Conclusions: AT and PC show decreased recovery and t½ in the fetal lamb. These data can be used to estimate dosing for human neonates in comparison with human adult dosing recommendations.

© 2008 S. Karger AG, Basel

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: November 29, 2007
Accepted: May 19, 2008
Published online: November 27, 2008
Issue release date: June 2009

Number of Print Pages: 7
Number of Figures: 2
Number of Tables: 1

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: http://www.karger.com/NEO

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