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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 Mayer, E. J. Articles by Reilly, C. F. Search for Related Content PubMed PubMed Citation Articles by Mayer, E. J. Articles by Reilly, C. F. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  The pharmacokinetics of plasminogen activator inhibitor-1 in the rabbit EJ Mayer, T Fujita, SJ Gardell, RJ Shebuski and CF Reilly Department of Pharmacology, Merck Sharp and Dohme Research Laboratories, West Point, PA 19486. The pharmacokinetics of the activated and latent forms of plasminogen activator inhibitor-1 (PAI-1) isolated from HT1080 fibrosarcoma cells (HT1080 PAI-1) and a nonglycosylated form of human PAI-1 isolated from a yeast expression system (rPAI-1) were followed in the rabbit. As assessed by an immunologic assay specific for human PAI-1, guanidine HCI activated HT1080 PAI-1 and rPAI-1 entered the total plasma volume following intravenous bolus administration and exhibited a biphasic clearance pattern. The t1/2s of HT1080 PAI-1 for the initial and beta phases equalled 6.0 and 24.8 minutes, respectively. The t1/2s of rPAI-1 for the initial and beta phases equalled 8.8 and 34.0 minutes, respectively. Similar results were obtained by measuring PAI-1 activity in plasma and with trace amounts of 125I-rPAI-1, suggesting that the above pharmacokinetic behavior could also apply to endogenous PAI-1. The liver was the main site of rPAI-1 clearance. Unactivated, latent PAI-1 exhibited a very different pharmacokinetic profile. Over 80% of latent rPAI-1 cleared from the circulation within 10 minutes (t1/2 = 1.7 minutes). The difference in clearance behavior between activated and latent PAI-1 may be related to the ability of activated PAI-1, but not latent PAI-1, to rapidly form high-molecular-weight complexes with plasma binding factors which were observed in vitro and in vivo. Because PAI-1 could potentially tilt the fibrinolytic balance toward a prothrombotic state, its rapid clearance may represent an important control mechanism governing the circulating levels of this key component of the fibrinolytic pathway. Volume 76, Issue 8, pp. 1514-1520, 10/15/1990 Copyright © 1990 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: D. J. Schneider, P. M. Absher, and M. A. Ricci Dependence of Augmentation of Arterial Endothelial Cell Expression of Plasminogen Activator Inhibitor Type 1 by Insulin on Soluble Factors Released From Vascular Smooth Muscle Cells Circulation, November 4, 1997; 96(9): 2868 - 2876. [Abstract] [Full Text]

	Copyright © 1990 by American Society of Hematology         Online ISSN: 1528-0020