Saivin S, Caranobe C, Petitou M, Sie P, Lormeau J C, Level M, Crepon B, Houin G, Boneu B
Unité de Pharmacocinétique, Hôpital Purpan, Toulouse, France.
Br J Haematol. 1992 Apr;80(4):509-13. doi: 10.1111/j.1365-2141.1992.tb04565.x.
This paper compares the pharmacological properties of a new succinyl dermatan sulphate derivative (Suc-DS) to those of the natural dermatan sulphate (DS). Suc-DS was on average 2-3 times more potent than DS in catalysing the inhibition of thrombin by heparin cofactor II and in prolonging the activated partial thromboplastin time and the thrombin clotting time. After bolus injection, Suc-DS was also 2-3 times more potent than DS to prevent experimental venous thrombosis in a Wessler model. Thromboplastin or human serum were used as the thrombogenic stimulus. In contrast, the bleeding effect assessed by rat tail transection technique was comparable. After bolus intravenous injection, the pharmacodynamics of Suc-DS indicated a lower volume of distribution, which was close to the plasma volume, and a slightly lower clearance of elimination. Therefore this chemical alteration of natural DS yields a new compound with an improved antithrombotic benefit/haemorrhagic risk ratio.
本文比较了一种新型琥珀酰硫酸皮肤素衍生物（Suc-DS）与天然硫酸皮肤素（DS）的药理学特性。在催化肝素辅因子II抑制凝血酶以及延长活化部分凝血活酶时间和凝血酶凝血时间方面，Suc-DS的效力平均比DS高2至3倍。在推注给药后，在Wessler模型中，Suc-DS预防实验性静脉血栓形成的效力也比DS高2至3倍。凝血活酶或人血清用作血栓形成刺激物。相比之下，通过大鼠尾部横断技术评估的出血效应相当。静脉推注给药后，Suc-DS的药效学表明其分布容积较低，接近血浆容积，消除清除率略低。因此，天然DS的这种化学改变产生了一种抗血栓形成效益/出血风险比得到改善的新化合物。
