In vitro amiodarone protein binding and its interaction with warfarin

Summary The binding of amiodarone to human plasma protein and to bovine serum, albumin was studied by three different methods, ultracentrifugation, equilibrium dialysis and fluorescence spectroscopy. The fraction of amiodarone bound to plasma protein amounted to 96.3%. The changes in the binding properties of 1-anilino-naphthalene-8-sulfonate for bovine serum albumin using warfarin and amiodarone as independent inhibitors were analyzed in terms of binding site specificity. The findings indicated that amiodarone and warfarin have two different binding sites on bovine serum albumin, so a noncompetitive inhibition mechanism was indicated. On the basis of our data we cannot exclude other mechanisms of interaction besides direct displacement of one drug by another; nevertheless, metabolite interference between amiodarone and coagulation cofactors may better explain the enhancement of warfarin's pharmacological action in association with amiodarone.This work was partially funded by the CNR (National Research Council, Rome, Italy), Program on Clinical Pharmacology and Rare Diseases. The authors would like to thanks Drs E. Marzi and E. riva for their help.     

抗凝血药物华法灵钠与人血清白蛋白的相互作用研究

用荧光光谱、紫外光谱和圆二色谱法研究了抗凝血药物华发灵钠与人血清白蛋白(HSA)的相互作用.初步确定华法灵钠对人血清白蛋白的荧光产生猝灭现象,猝灭方式为静态,并计算了二者形成化合物的结合常数K和结合位点数n.根据不同温度下的热力学函数,确定了华发灵钠与人血清白蛋白的相互作用力类型为氢键和范德华力.发现华法灵钠的存在明显改变人血清白蛋白的构象,并讨论了华发灵钠使人血清白蛋白构象发生变化的可能原因.     

疏血通注射液联合低分子肝素、华法令治疗肺栓塞的临床观察

目的探讨疏血通注射液联合低分子肝素及华法令抗凝治疗肺栓塞的临床疗效及安全性。方法选取急性肺栓塞住院患者81例,分为2组:疏血通联合低分子肝素、华法令治疗组为试验组,共48例;低分子肝素及华法令治疗组为对照组,共33例。通过比较2组治疗后临床症状,血气分析结果,肺动脉CT或核素通气/灌注恢复情况,了解治疗效果。通过比较凝血指标,了解治疗的安全性。结果治疗7 d,试验组临床症状改善率为83.33%,对照组为66.64%,2组比较差异有统计学意义。治疗14 d临床症状改善情况及通气指标,凝血指标比较,2组均无显著差异。结论疏血通联合抗凝治疗在治疗7d的临床症状改善方面优于单纯抗凝治疗组,且治疗安全性好。     

华法令和阿斯匹林预防心房颤动并发血栓栓塞的比较研究

目的探讨心房颤动患者抗凝治疗的重要性,以降低血栓栓塞事件的发生率。方法对2001年5月—2003年11月在我院治疗的132例房颤患者,给予口服阿司匹林治疗的69例,口服华法令治疗的63例。对两组患者随访1年的血栓栓塞事件发生率进行对比分析。结果经用华法令抗凝,INR达到2.0~3.0后,其血栓栓塞事件发生率较服用阿司匹林治疗明显下降。抗凝治疗者出现1例上消化道出血(P<0.01),无出血性死亡病例。结论华法令对降低心房颤动所致血栓栓塞性事件发生率有效,是提高心房颤动患者的生存率的有效治疗措施之一。