Pharmacokinetic and Antithrombotic Properties of Two Pentasaccharides With High Affinity to Antithrombin 111 in the Rabbit: Comparison
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چکیده
This study compares the pharmacokinetic and the antithrombotic properties of two pentasaccharides with high affinity to antithrombin 111 with those of a conventional low molecular weight heparin, CY216, in the rabbit. On a weight basis, SR 90107A/ORG 31540 (natural pentasaccharide [NPSI) and SR 80027A/ORG 31550 (sulfated pentasaccharide [SPS]) were, respectively, 4.7 and 26 times more potent antifactor Xa inhibitory agents than CY216. They were devoid of antithrombin activity, whereas the antifactor Xalantithrombin ratio of CY216 was 3.8. After bolus intravenous administration, the clearance (mL/kg/h) of CY216 decreased from 91 ? 27 for the dose of 12.5 U/kg to 49 f 14 for the dose of 50 U/kg and then remained constant up to the highest dose tested (500 U/kg). The clearance of NPS was unrelated to the dose and comparable to that of CY216 over 50 U/kg, whereas that of SPS was 10 times lower. Consistent results were observed after continuous intravenous infusions for 9 hours and subcutaneous administration. The duration of the antithrombotic effect was compared after a single subcutaneous injection of 250 U/kg of either compound in the stasis-Wessler model using human serum as thrombogenic stimulus. Two hours after the injection, the three compounds provided a thrombus prevention of
منابع مشابه
Synthetic heparin-like antithrombotics
After the discovery of a unique pentasaccharide domain in heparin that is responsible for activation of antithrombin 111, many analogues have been synthesised which stimulate the inhibition of factor Xa. Some aspects of the synthesis of heparin like pentasaccharides are presented. Furthermore, pentasaccharide conjugates could be designed and synthesised which stimulate the antithrombin I11 medi...
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