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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dol, F. Articles by Boneu, B. Search for Related Content PubMed PubMed Citation Articles by Dol, F. Articles by Boneu, B. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Pharmacodynamics and pharmacokinetics of dermatan sulfate in humans F Dol, G Houin, M Rostin, JL Montastruc, D Dupouy, F Gianese, P Sie and B Boneu Laboratoire d'Hemostase, Centre de Transfusion Sanguine, Hopital Purpan, Toulouse, France. Dermatan sulfate (DS), a catalyst of the thrombin-heparin cofactor II interaction, has antithrombotic activity and is devoid of significant hemorrhagic risk in several animal models. We investigated the pharmacodynamic and pharmacokinetic properties of DS in humans. DS was injected in single bolus intravenous injections of four increasing doses (0.5, 1, 1.5, 2 mg/kg) to six healthy volunteers. The resulting anticoagulant activities were assessed by the activated partial thromboplastin time (APTT) and the thrombin clotting time (TCT). There were dose-dependent prolongations of the APTT and TCT, and the anticoagulant activities disappeared in less than three hours. The pharmacokinetic parameters were calculated from the plasma concentrations of DS measured with a new chromogenic assay. The volume of distribution was approximately 1.8 times greater than the theoretical plasma volume and was independent of dose. In contrast, the clearance decreased with dose and the terminal half-life ranged from 0.45 +/- 0.08 hours at 0.5 mg/kg to 0.72 +/- 0.11 hours (mean +/- SD) at 2 mg/kg. The bioavailabilities of subcutaneous (SC) and intramuscular (IM) administration relative to those of intravenous administration were determined in 12 other volunteers. The respective bioavailabilities were 24.7% +/- 12.9% and 12.4% +/- 9.2% for SC and IM administration. There was no detectable change in the APTT and the TCT when the volunteers were injected with 1.5 mg/kg SC or IM. In addition, the pharmacokinetic parameters derived from plasma concentrations of DS showed considerable interindividual variations by the two later routes of administration. Peak concentrations were noted 2.7 +/- 1.3 hours after SC injection and 4.3 +/- 4.9 hours after IM injection. The average peak concentrations were 0.7 +/- 0.3 and 0.4 +/- 0.2 mg/L after SC and IM injections, respectively. The half-lives of DS were 7.9 +/- 6.5 hours (SC) and 6.3 +/- 7.4 hours (IM). No adverse reaction to DS was recorded during this study. Volume 74, Issue 5, pp. 1577-1582, 10/01/1989 Copyright © 1989 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. M. Andreozzi, S. Signorelli, L. Di Pino, R. Martini, E. Marchitelli, A. Pinto, S. Romeo, V. Zamboni, and E. Palazzini Tolerability and Clinical Efficacy of Desmin in the Treatment of Superficial Thrombovaricophlebitis Angiology, September 1, 1996; 47(9): 887 - 894. [Abstract] [PDF]

	Copyright © 1989 by American Society of Hematology         Online ISSN: 1528-0020