A CROSS-OVER COMPARISON OF THE ANTI-CLOTTING EFFECTS OF 3 LOW-MOLECULAR-WEIGHT HEPARINS AND GLYCOSAMINOGLYCURONAN

1 The anti-clotting effects after intravenous administration of three low molecular weight (LMW) heparins, Fragmin(R) (KABI 2165), Fraxiparine(R) (CY 216), Clexane(R) (PK 10169) and the LMW mixture of glycosaminoglycuronans Orgaran(R) (Org 10172) were compared in a randomized cross-over study in 12 healthy male volunteers. 2 The time courses of the anti-Xa activity of Fragmin(R), Fraxiparine(R) and Clexane(R) (five subjects) were best fitted by a monoexponential function and had comparable half-lives of 1.9 h, 2.3 h and 2.8 h, respectively. The time courses of the anti-Xa activity of Orgaran(R) and Clexane(R) (four subjects) were described by a biexponential function with terminal half-lives of 56.8 h and 27.7 h, respectively. They were longer than those of Fraxiparine(R) and Fragmin(R). Orgaran(R) injection was associated with a significantly smaller 'clearance' (0.8 +/- 0.2 1 h-1) of the plasma anti-Xa activity compared with Fragmin(R) (2.0 +/- 0.5), Fraxiparine(R) (1.7 +/- 0.5) and Clexane(R) (1.6 +/- 0.5). 3 In comparison with the three LMW heparins, the terminal half-life of plasma anti-IIa activity after Orgaran(R) was longer and the 'clearance' of Orgaran(R) was lower than that after Clexane(R). The area under the curve of the plasma anti-IIa activity after administration of Orgaran(R) was negligible compared with that obtained after injection of the LMW heparins. 4 Orgaran(R) caused the smallest and Fragmin(R) the greatest prolongation of the activated partial thromboplastin time (Orgaran(R) 5.8 +/- 1.2 s vs Fragmin(R) 18.5 +/- 5.2 s) and the thrombin clotting time (Orgaran(R) 2.9 +/- 1.7 s vs Fragmin(R) 47.8 +/- 0.9 s). 5 The LMW heparins clearly differ kinetically from each other and from the low molecular weight compound Orgaran(R). Until the clinical importance of these differences is known, the low molecular weight heparins cannot be considered as an undifferentiated group of drugs.