O'Reilly R A
Circulation. 1982 Jan;65(1):202-7. doi: 10.1161/01.cir.65.1.202.
Although serious hemorrhage during therapeutic coadministration of sulfinpyrazone and racemic warfarin occurs, no prospective studies have been done. In this study, single oral doses of racemic warfarin, 1.5 mg/kg, were administered to six normal subjects with and without oral sulfinpyrazone, 400 mg daily. Both the hypoprothrombinemia (p less than 0.001) and the plasma warfarin concentrations (p less than 0.05) were significantly augmented. To determine if this interaction was stereoselective, the experiments were repeated in the same subjects with R-and S-warfarin enantiomorphs. S-warfarin with sulfinpyrazone caused a highly significant augmentation of both the hypoprothrombinemia (p less than 0.001) and the plasma warfarin concentrations (p less than 0.001). R-warfarin with sulfinpyrazone did not significantly change the hypoprothrombinemia but significantly (p less than 0.05) reduced warfarin concentrations. Thus, sulfinpyrazone augmented the hypoprothrombinemia of racemic warfarin stereoselectively by reduced metabolic clearance of S-warfarin. Sulfinpyrazone and racemic warfarin are most dangerous when either drug is added to a stabilized regimen of the other drug.
尽管在亚磺吡啶酮与消旋华法林联合治疗期间会发生严重出血，但尚未进行前瞻性研究。在本研究中，给6名正常受试者单次口服1.5mg/kg的消旋华法林，其中3名受试者同时每日口服400mg亚磺吡啶酮。结果显示，联合用药组的低凝血酶原血症（p<0.001）及血浆华法林浓度（p<0.05）均显著升高。为确定这种相互作用是否具有立体选择性，对相同受试者分别给予R-华法林对映体和S-华法林对映体重复上述实验。结果发现，S-华法林与亚磺吡啶酮联合使用导致低凝血酶原血症（p<0.001）和血浆华法林浓度（p<0.001）均极显著升高。R-华法林与亚磺吡啶酮联合使用未显著改变低凝血酶原血症，但显著降低了华法林浓度（p<0.05）。因此，亚磺吡啶酮通过降低S-华法林的代谢清除率，立体选择性地增强了消旋华法林的低凝血酶原血症。当两种药物中的任何一种添加到另一种药物的稳定治疗方案中时，亚磺吡啶酮和消旋华法林联用最为危险。
