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SummaryThe antithrombotic and haemostatic effects of a pentasaccharide, the chemically synthesized antithrombin III (AT-III) binding fragment of heparin (PENTA), were investigated in rats in comparison with heparin. PENTA showed a dose-dependent antithrombotic effect in three thrombosis models in which thrombus formation was induced by different triggers. PENTA was consistently less potent than heparin in these models if doses were expressed in anti-Xa U/kg but PENTA showed more or less the same potency as heparin if doses were expressed in mg/kg. The antithrombotic effect of PENTA was strongly related to its anti-Xa activity as judged from its antithrombotic potency in the various models and from the time courses of both activities. PENTA caused a dose-dependent increase in blood loss in a bleeding model but the dose response curve was rather flat; the effect of PENTA on blood loss was small compared to that of heparin. The duration of action of PENTA as measured by the plasma anti-Xa levels was long compared to that of heparin and the duration of the antithrombotic effect was that expected on the basis of the plasma anti-Xa levels.Finally, PENTA showed comparable antithrombotic activity after s.c. and i.v. administration, as expected because of the approximately 100% bioavailability of the anti-Xa activity after s.c. administration.

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1. In a cross-over study a new low molecular weight heparinoid Org 10172 was administered to 12 elderly male and female volunteers. It was well tolerated and no adverse effects occurred. 2. The absolute bioavailability of Org 10172 as measured by plasma anti-Xa activity, glycosaminoglycuronans with no affinity to antithrombin III (NoA-GAG) and thrombin generation inhibiting activity approached 100% in both sexes. 3. The half-life of elimination of its anti-Xa activity (19.2 +/- 6.1 h) was similar to that found previously in young volunteers. Org 10172 was further characterised by a rapid disappearance from the circulation of its anti-thrombin activity (t1/2 1.8 +/- 0.6 h) and of the NoA-GAG (t1/2 3.5 +/- 2.1 h). 4. Its thrombin generation inhibiting activity was of intermediate duration (t1/2 elimination 6.2 +/- 4.0 h).