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Characterization of Total Plasma Glycosaminoglycan Levels in Healthy Volunteers Following Oral Administration of a Novel Antithrombotic Odiparcil With Aspirin or Enoxaparin

From the Pharmacokinetics/Biopharmaceutics Laboratory, School of Pharmacy, University of Maryland, Baltimore, Maryland.

Odiparcil is a novel, orally active β-D-thioxyloside analog with antithrombotic activity associated with a reduced risk of adverse bleeding events. Its unique mechanism of action is postulated by means of an elevation in circulating endogenous chondroitin sulfate-related glycosaminoglycans (GAGs) levels. The purpose of these 2 separate clinical studies was to evaluate plasma GAG levels in healthy subjects administered odiparcil with either aspirin (ASA) or enoxaparin. Clinical plasma samples were processed and analyzed using validated HPLC bioassays that indirectly estimate GAG levels based on the simultaneous detection of the chondroitin disaccharide derivatives. The concomitant administration of odiparcil with or without ASA resulted in a significant elevation in GAG levels over baseline for both treatment groups. In the other clinical study, the concomitant administration of odiparcil with or without enoxaparin displayed significant increases in plasma Di-OS, Di-4S, and total disaccharide levels versus control group. Neither plasma GAG levels nor odiparcil plasma levels were correlated with a rise in hepatic transaminases, an adverse drug event observed in several subjects; and plasma odiparcil levels were indirectly correlated with plasma GAG levels. These clinical studies were proof of concept of preclinical rat studies indicating that chronic odiparcil treatment elevates endogenous GAG levels in human subjects.

Key Words: Odiparcil • glycosaminoglycans • antithrombotics • β-D-thioxylosides • chondroitin sulfate

Address for reprints: Dr Natalie D. Eddington, Dean, School of Pharmacy, University of Maryland at Baltimore, 20 North Pine Street, Room 730, Baltimore, MD 21201-1142; e-mail: neddingt{at}rx.umaryland.edu.

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