Partial in vivo neutralisation of plasma anticoagulant effects of Lomoparan (Org 10172) by protamine chloride.
In a cross-over study increasing doses of protamine hydrochloride (20-100 mg) or placebo were administered to six groups of four healthy male volunteers each, following a single intravenous dose of 3200 anti-Xa units of Org 10172. No neutralising effects were observed on the Org 10172 induced changes in the bleeding time, prothrombin time and thrombin time. A small and statistically not significant temporary decrease in anti-Xa activity was observed after doses of 80 and 100 mg protamine chloride. The anti-thrombin activity was dose-dependently and partly irreversibly neutralised by protamine chloride to a maximum of approximately 60%. This neutralisation correlated with the observed shorter prolongation of the thrombin time. The thrombin-generation inhibition activity was for approximately 35% neutralised by protamine chloride doses of 60-100 mg.
Stiekema
J C
JC
Organon International B.V., Scientific Development Group, Oss, The Netherlands.
Wijnand
H P
HP
ten Cate
H
H
ten Cate
J W
JW
Harenberg
J
J
Egberts
J F
JF
van Dinther
T G
TG
D000293:Adolescent; D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D065427:Factor Xa Inhibitors; D006025:Glycosaminoglycans / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000494:pharmacology; D006497:Heparan Sulfate; D006801:Humans; D008297:Male; D010314:Partial Thromboplastin Time; D011479:Protamines / Q000008:administration & dosage / Q000494:pharmacology*; D011516:Prothrombin / Q000037:antagonists & inhibitors; D011517:Prothrombin Time; D013918:Thrombin Time
D000925:Anticoagulants; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D065427:Factor Xa Inhibitors; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D011479:Protamines; D011516:Prothrombin; C025337:Factor IIa; C035838:danaparoid