Markwardt F, Nowak G, Stürzebecher J, Vogel G
Institute of Pharmacology and Toxicology, Medical Academy Erfurt, G.D.R.
Thromb Res. 1988 Dec 1;52(5):393-400. doi: 10.1016/0049-3848(88)90023-0.
The pharmacokinetics of recombinant hirudin were studied in 9 healthy subjects after single intravenous, subcutaneous or intramuscular doses of 0.1 mg/kg. Generally, administration of r-hirudin was tolerated without side effects. An assay was used which detects the inhibitor in blood and urine by its antithrombin activity. Absorption, distribution and elimination of r-hirudin were found to be corresponding to the results obtained with native hirudin. The effects on the haemostatic system were evaluated. Thrombin time and partial thromboplastin time were prolonged dependent on the r-hirudin plasma level. Platelet counts, fibrinogen level and fibrinolytic system were unchanged. Bleeding time was not prolonged. After administration of r-hirudin in case of chronic DIC, fibrinogen level, platelet counts and fibrin monomers transiently returned to normal values.
在9名健康受试者中，静脉内、皮下或肌肉内单次给予0.1mg/kg重组水蛭素后，对其药代动力学进行了研究。一般来说，给予重组水蛭素耐受性良好，无副作用。采用一种通过抗凝血酶活性检测血液和尿液中抑制剂的测定方法。发现重组水蛭素的吸收、分布和消除与天然水蛭素的结果一致。评估了其对止血系统的影响。凝血酶时间和部分凝血活酶时间根据重组水蛭素血浆水平而延长。血小板计数、纤维蛋白原水平和纤溶系统未改变。出血时间未延长。在慢性弥散性血管内凝血（DIC）病例中给予重组水蛭素后，纤维蛋白原水平、血小板计数和纤维蛋白单体短暂恢复到正常值。
