The Beneficial Effect of a β-D-Xyloside, Iliparcil, in the Prevention of Postthrombolytic Rethrombosis in the Rat

Abstract

The effect of Iliparcil, a new orally active β-D-xyloside venous antithrombotic, was studied on the rethrombosis following thrombolytic therapy in rats, using a modified Umetsu model. The drug was administered by oral route prior to thrombolytic therapy, which consisted of administering a combination of heparin and urokinase (H/U) at 37.5 and 70,000 IU/kg, respectively. Time to reocclusion increased from 3.9 min with saline to 10.5 min following H/U injection. When Iliparcil (30 mg/kg, oral route) was administered 4 h before H/U injection, the time to reocclusion was increased by 250% compared with H/U alone (p < 0.001). Similarly, dermatan sulfate (DS), administered intravenously (3 mg/kg) 5 min before thrombus induction, also increased the time to reocclusion (300% compared with H/U alone; p < 0.001). It was also shown that times to reocclusion following Iliparcil or DS treatments were still increased even when heparin dosage was decreased. These results suggest that an antithrombotic product derived from the β-D-xyloside family could be advantageously used in combination with thrombolytic treatment instead of heparin, which causes complications and side effects.

A comparison of the β‐D‐xyloside, odiparcil, to warfarin in a rat model of venous thrombosis

“…In the following report, the xyloside approach has been further investigated with the novel β ‐D‐thioxyloside odiparcil. Odiparcil is an orally active antithrombotic agent currently in clinical studies, and is the result of a medicinal chemistry effort, based on the learnings from predecessor molecules [13,18], aimed at optimizing the antithrombotic, clinical pharmacokinetic (PK), and overall developability profile of xylosides.…”

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

“…Odiparcil (SB‐424323; Figure 1) is a novel orally active β‐ d ‐thioxyloside antithrombotic compound chemically similar to its predecessor congeners naroparcil 15 , 16 and iliparcil 17 . In a recent phase IIa study TEMPEST (ThromboEMbolism Prevention Efficacy and Safety Trial), odiparcil 125 mg or 500 mg twice daily was administered to patients (n = 225) undergoing total hip replacement surgery.…”

Safety and Efficacy Assessment of Chungpyesagan-tang for Acute Ischemic Stroke

“…It is used in nearly every current acute stroke study in the United States as a measure of the initial and final neurological deficit. The MBI is a commonly used scale that measures disability or dependence in activities of daily living in stroke patients (Engberg et al, 1995;Sulter et al, 1999;de Haan et al, 1993).…”

“…Ligustici radix decreases ischemic necrosis rate by promoting microcirculation, preventing clot formation, and reducing exudation and hemorrhage (Chen, 1993). Beta-D-xyloside in Cimicifugae rhizoma has proven to increase the re-occlusion time after thrombolytic therapy in rats (Chicaud et al, 1998;Koeda et al, 1995). Angelicae radix has anti-platelet aggregation effect (Shimizu et al, 1991).…”