A novel anti-thrombotic heparinoid (Org 10172) devoid of bleeding inducing capacity: a survey of its pharmacological properties in experimental animal models.
The pharmacological profile of Org 10172, a mixture of sulphated glycosaminoglycorunans derived from hog intestinal mucosa, has been assessed in experimental thrombosis and bleeding models in rats and compared with heparin USP. Org 10172 inhibited thrombus formation in arterio-venous shunts dose dependently, the dose required for 50% inhibition (ID50) of thrombus formation was 40 anti-Xa units/kg i.v. The ID50 for heparin USP was 70 anti-Xa units/kg i.v. Org 10172 hardly increased bleeding in doses upto 1600 anti-Xa units/kg i.v., whereas heparin USP dose dependently increased bleeding from 90 anti-Xa units/kg i.v. onwards. The benefit (anti-thrombotic)/risk (bleeding) ratio of Org 10172 was therefore considerably better than that of heparin USP. The improved profile of Org 10172 towards bleeding might be caused by differences in the interaction with blood platelets in comparison with heparin USP. Org 10172 had less effect on the platelet content in thrombi than heparin USP. Org 10172 did not inhibit collagen induced release of serotonin in contrast to heparin USP. Org 10172 inhibited factor Xa induced aggregation of rabbit platelets but only at anti-Xa levels which were fifteen times higher than for heparin USP. In contrast to heparin USP Org 10172 had only a very weak effect on the activated partial thromboplastin time (APTT) ex vivo.
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006496:Heparinoids / Q000009:adverse effects / Q000494:pharmacology*; D006497:Heparan Sulfate; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013924:Thrombophlebitis / Q000188:drug therapy
D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D005343:Fibrinolytic Agents; D006025:Glycosaminoglycans; D006493:Heparin; D006496:Heparinoids; D006497:Heparan Sulfate; C035838:danaparoid