Dupe R J, Green J, Smith R A
Thromb Haemost. 1985 Feb 18;53(1):56-9.
A procedure is described for the establishment of experimental clots, aged in vivo for 72 hr, in the jugular vein of beagle dogs. Two acylated derivatives of streptokinase-human (lys) plasminogen activator complex with greatly differing deacylation rates under physiological conditions were compared as thrombolytic agents in the model. These were BRL 26921 (deacylation half-life, 40 min) and BRL 33575 (deacylation half-life c. 17 hr). The pharmacokinetic clearance rate of BRL 33575 from the circulation was studied and gave a clearance half-life of about 7 hr. BRL 33575 was found to be the superior agent in lysing 72 hr aged clots, being effective at a single bolus dose of 420 micrograms/kg or in three equal divided doses of 140 micrograms/kg given at 12 hr intervals. The single dose regime gave moderate systemic plasminogen activation, and the effect was significantly reduced with the divided dose regime. Infusion of freshly formed streptokinase-human plasminogen activator complex at 420 micrograms/kg over 15 hr gave little thrombolysis despite marked systemic plasminogen activation.
本文描述了一种在比格犬颈静脉中建立体内老化72小时的实验性血栓的方法。比较了两种在生理条件下脱酰化速率差异很大的链激酶-人（赖氨酸）纤溶酶原激活剂复合物的酰化衍生物作为该模型中的溶栓剂。它们分别是BRL 26921（脱酰化半衰期为40分钟）和BRL 33575（脱酰化半衰期约为17小时）。研究了BRL 33575从循环中的药代动力学清除率，其清除半衰期约为7小时。结果发现，BRL 33575在溶解72小时老化血栓方面是更优的药物，单次推注剂量为420微克/千克或按12小时间隔分三次等量给予140微克/千克时均有效。单次给药方案引起适度的全身纤溶酶原激活，而分次给药方案的效果则显著降低。以420微克/千克的剂量在15小时内输注新鲜形成的链激酶-人纤溶酶原激活剂复合物，尽管有明显的全身纤溶酶原激活，但溶栓效果甚微。
