The pharmacodynamics of tinzaparin in healthy volunteers

We report the pharmacodynamic properties of tinzaparin (175 U/kg antifactor Xa) given as a single daily administration for 5 consecutive days to 14 healthy volunteers as a known safe, effective treatment of deep vein thrombosis and pulmonary embolism. The CM,X for antifactor Xa (0.87+/-0.15 U/ml) was associated with a 2.4+/-0.5-fold prolongation of the activated partial thromboplastin time (APTT) and a high antithrombin activity (0.38+/-0.1 U/ml), The C-max value of antifactor Xa was 1.15- and twofold lower than those generated by similar doses of nadroparin and enoxaparin respectively. The clearance of antifactor Xa activity (1.29+/-0.2 1/h) was 1.5- and twofold greater than those reported for nadroparin and enoxaparin respectively. These results indicated that the antithrombotic and prohaemorrhagic effects of a low molecular weight heparin were independent from the absolute levels of antifactor Xa activities and from the prolongation of the APTT.