Primus Pharmaceuticals, Inc., Scottsdale, AZ 85251, USA.
Adv Ther. 2010 Jun;27(6):400-11. doi: 10.1007/s12325-010-0040-7. Epub 2010 Jun 16.
Flavocoxid, a botanical, anti-inflammatory agent, nonspecifically inhibits the peroxidase activity of cyclooxygenase (COX-1 and COX-2) enzymes and 5-lipooxygenase (5-LOX). Due to the concomitant use of aspirin or warfarin in many osteoarthritis (OA) patients with increased cardiovascular risk, we felt it necessary to assess the anticoagulation properties of flavocoxid.
Three different studies were used: 1) a mouse model to assess effects on bleeding times when combined with aspirin; 2) the effect on platelet function as evaluated by platelet aggregation and bleed times in healthy human subjects; and 3) the effect on international normalized ratio in previously warfarinized patients with OA.
Flavocoxid at a human equivalent dose (HED) of 569 mg (within the standard human dosing range of 500 mg) produced no significant increases in bleeding time in mice. There was also no inhibition or synergistic increase in bleed times when flavocoxid was combined with aspirin (370 mg HED). Flavocoxid did not significantly inhibit thromboxane production or platelet aggregation, and did not increase bleeding times in healthy volunteers. Finally, flavocoxid did not inhibit or potentiate the anticoagulant effect of warfarin.
These results suggest that flavocoxid does not affect the primary or extrinsic pathways of secondary hemostasis and, by not inhibiting the anticoagulation effects of aspirin, may have utility in cardiovascular patients with OA.
Flavocoxid 是一种植物性抗炎剂,非特异性抑制环氧化酶(COX-1 和 COX-2)和 5-脂氧合酶(5-LOX)的过氧化物酶活性。由于许多患有心血管风险增加的骨关节炎(OA)患者同时使用阿司匹林或华法林,我们认为有必要评估 flavocoxid 的抗凝特性。
使用了三项不同的研究:1)评估与阿司匹林联合使用时对出血时间的影响的小鼠模型;2)在健康人体受试者中评估血小板聚集和出血时间对血小板功能的影响;3)评估先前使用华法林的 OA 患者对国际标准化比值的影响。
Flavocoxid 的人体等效剂量(HED)为 569mg(在 500mg 的标准人体剂量范围内),在小鼠中未导致出血时间显著延长。当 flavocoxid 与阿司匹林(370mg HED)联合使用时,也没有抑制或协同增加出血时间。Flavocoxid 未显著抑制血栓素的产生或血小板聚集,也未增加健康志愿者的出血时间。最后,flavocoxid 既不抑制也不增强华法林的抗凝作用。
这些结果表明 flavocoxid 不会影响二期止血的主要或外在途径,并且由于它不抑制阿司匹林的抗凝作用,因此可能对患有 OA 的心血管病患者具有实用性。