Saivin S, Caranobe C, Petitou M, Lormeau J C, Houin G, Boneu B
Laboratoire d'Hémostase, Centre de Transfusion Sanguine, Toulouse, France.
Thromb Haemost. 1992 May 4;67(5):550-5.
This paper reports on the pharmacodynamic properties of butyryl derivatives of unfractionated heparin (C4-UH) and of low molecular weight heparin (C4-CY 216) after bolus intravenous injection, constant infusion and subcutaneous administration to rabbits. The pharmacodynamic properties of the two butyryl derivatives were compared to those of the parent compounds, unfractionated heparin (UH) and low molecular weight heparin (CY 216). After bolus intravenous injection of increasing doses, the disposition of the butyryl derivatives were comparable to that of their parent compounds up to 3 mg kg-1. Over this dose, their clearances became 2 to 3 times lower. These long lasting properties were confirmed by constant intravenous infusion experiments. After subcutaneous administration, the bioavailability of C4-UH remained low (10%) at any dose while that of C4-CY 216 ranged from 42 to 120%. If these findings are confirmed in man, these new derivatives open the possibility of treating established deep vein thrombosis with only one daily injection of a butyryl derivative of low molecular weight heparin.
本文报道了未分级肝素（C4-UH）和低分子量肝素（C4-CY 216）的丁酰基衍生物在大剂量静脉注射、持续输注及皮下注射给家兔后的药效学特性。将这两种丁酰基衍生物的药效学特性与其母体化合物未分级肝素（UH）和低分子量肝素（CY 216）的药效学特性进行了比较。在大剂量静脉注射递增剂量后，直至3 mg kg-1，丁酰基衍生物的处置情况与其母体化合物相当。超过此剂量，它们的清除率降低2至3倍。这些长效特性通过持续静脉输注实验得到证实。皮下给药后，C4-UH在任何剂量下的生物利用度均较低（10%），而C4-CY 216的生物利用度范围为42%至120%。如果这些发现在人体中得到证实，这些新衍生物为仅通过每日注射一次低分子量肝素的丁酰基衍生物来治疗已形成的深静脉血栓形成提供了可能性。
