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.
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- Protein C
- Replacement protein
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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 firstname.lastname@example.org
Received: November 29, 2007
Accepted after revision: May 19, 2008
Published online: November 27, 2008
Number of Print Pages : 7
Number of Figures : 2, Number of Tables : 1, Number of References : 41
Neonatology (Fetal and Neonatal Research)
Vol. 95, No. 4, Year 2009 (Cover Date: June 2009)
Journal Editor: Halliday H.L. (Belfast), Speer C.P. (Würzburg)
ISSN: 1661–7800 (Print), eISSN: 1661–7819 (Online)
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