A cross-over comparison oftheanti-clotting effects ofthree low molecular weight heparins andglycosaminoglycu ronan

1 Theanti-clotting effects after intravenous administration ofthree lowmolecular weight (LMW)heparins, Fragmin® (KABI2165), Fraxiparine® (CY216), Clexane® (PK10169) andtheLMW mixture ofglycosaminoglycuronans Orgaran (Org10172) werecompared inarandomized cross-over study in12healthy malevolunteers. 2 Thetimecourses oftheanti-Xa activity ofFragmin®, Fraxiparine® andClexane® (five subjects) werebestfitted byamonoexponential function andhadcomparable half-lives of1.9h,2.3hand2.8h,respectively. Thetimecourses oftheanti-Xa activity ofOrgaran® andClexane® (four subjects) weredescribed byabiexponential function with terminal half-lives of56.8 hand27.7h,respectively. Theywerelonger thanthose ofFraxiparine® andFragmin®. Orgaran® injection wasassociated withasignificantly smaller 'clearance' (0.8 ± 0.21h-1) oftheplasma anti-Xa activity compared with Fragmin® (2.0 ± 0.5), Fraxiparine® (1.7 ± 0.5) andClexane® (1.6 ± 0.5). 3 Incomparison with thethree LMW heparins, theterminal half-life ofplasma anti-Ila activity after Orgaran® waslonger andthe'clearance' ofOrgaran® waslower than thatafter Clexane®. Theareaunderthecurveoftheplasma anti-Ia activity after administration ofOrgaran® wasnegligible compared withthat obtained after injection oftheLMW heparins. 4 Orgaran® caused thesmallest andFragmin® thegreatest prolongation oftheactivated partial thromboplastin time(Orgaran® 5.8± 1.2svsFragmin® 18.5 ± 5.2s)andthe thrombin clotting time(Orgaran® 2.9± 1.7svsFragmin® 47.8± 0.9s). 5 TheLMW heparins clearly differ kinetically fromeachother andfromthelow molecular weight compound Orgaran®. Until theclinical importance ofthese differencesisknown,thelowmolecular weight heparins cannot beconsidered asan undifferentiated group ofdrugs.