Login to MyKarger

New to MyKarger? Click here to sign up.

Login with Facebook

Forgot Password? Reset your password

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login (Shibboleth)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Table of Contents
Vol. 95, No. 4, 2009
Issue release date: June 2009
Section title: Original Paper
Free Access
Neonatology 2009;95:279–285

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
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
email 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

Do you have an account?

Login Information

Contact Information

I have read the Karger Terms and Conditions and agree.


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

Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.