Seiffge D, Weithmann K U
Thromb Res. 1987 Apr 15;46(2):371-83. doi: 10.1016/0049-3848(87)90299-4.
The effect of the combined oral administration of pentoxifylline (pof) and low dose acetylsalicylic acid (ASA) was evaluated with the help of the laser-induced thrombosis in rat mesenteric arterioles. Laser-induced thrombosis is inhibited in a dose-dependent way by both drugs. The administration of ASA, either simultaneously with or 1 hour prior to pof, does not show any effects in the laser model. On the contrary, the administration of pof followed 1 h later by ASA not only exhibited a significant effect but also produced a supraadditive inhibition of the laser-induced thrombus formation. Specific investigations concerning the time interval between the administration of both drugs determined that a significant effect can be achieved only after an interval of 30 to 90 minutes (principle of HWA 5112). The striking results could also be shown in diseased animals after sequential chronic administration of pof 1 h prior to ASA. HWA 5112 exhibits significant effects on laser-induced thrombus formation in the following chronic animal models: 1. adjuvant arthritic rats, 10----1 mg/kg for 21 days; 2. spontaneously hypertensive stroke-prone rats, 10----1 mg/kg three times within 24 h; 3. cholesterol-induced atherosclerosis in rabbits, 10----1 mg/kg for 14 days. The reported data clearly demonstrate that the sequential drug administration of first pentoxifylline followed 30 to 90 min later by ASA exhibits a supraadditive antithrombotic effect.
借助大鼠肠系膜小动脉激光诱导血栓形成模型，评估了己酮可可碱（pof）与低剂量阿司匹林（ASA）联合口服给药的效果。两种药物均以剂量依赖性方式抑制激光诱导的血栓形成。在激光模型中，与pof同时给药或在pof给药前1小时给予ASA均未显示出任何效果。相反，在pof给药1小时后给予ASA不仅表现出显著效果，而且对激光诱导的血栓形成产生了超相加性抑制作用。关于两种药物给药时间间隔的具体研究确定，仅在间隔30至90分钟后才能产生显著效果（HWA 5112原理）。在患病动物中，先给予pof 1小时后再给予ASA进行序贯慢性给药，也能得到显著结果。HWA 5112在以下慢性动物模型中对激光诱导的血栓形成具有显著作用：1. 佐剂性关节炎大鼠，10----1毫克/千克，给药21天；2. 自发性高血压易中风大鼠，10----1毫克/千克，24小时内给药三次；3. 兔胆固醇诱导的动脉粥样硬化模型，10----1毫克/千克，给药14天。报告的数据清楚地表明，先给予己酮可可碱，30至90分钟后再给予阿司匹林的序贯给药方式具有超相加性抗血栓作用。
