Imrecoxib is a registered treatment for osteoarthritis pain symptoms in China. This study aims to assess the effect of imrecoxib on the pharmacodynamics and pharmacokinetics of warfarin. 12 healthy male volunteers with CYP2C9*3 AA and VKORC1 AA genotypes took a 5 mg dose of warfarin both alone and concomitantly with steady-state imrecoxib. Both warfarin alone and concomitantly with imrecoxib have safey and good tolerance across the trial. Following warfarin and imrecoxib co-administration, neither Cmax, AUC0-t and t1/2 of warfarin enantiomers nor AUC of international normalized ratio (INR) were markedly different from those of warfarin alone. The geometric mean ratios (GMRs) (warfarin + imrecoxib: warfarin alone) of INR(AUC) was 1 (0.99, 1.01). The GMRs of warfarin AUC0-∞ (90% confidence interval, CIs) for warfarin + imrecoxib: warfarin alone were 1.12 (1.08, 1.16) for R-warfarin and 1.13 (1.07, 1.18) for S- warfarin. The 90% CIs of the GMRs of AUC0-∞, Cmax and INR (AUC) were all within a 0.8-1.25 interval. The combination of warfarin and imrecoxib did not impact the pharmacodynamics and pharmacokinetics of single-dose warfarin; therefore, when treating a patient with imrecoxib and warfarin, it is not required to adjust the dosage of warfarin.

译文

Imrecoxib是中国骨关节炎疼痛症状的注册治疗方法。本研究旨在评估伊瑞昔布对华法林药效学和药代动力学的影响。12名具有CYP2C9 * 3 AA和VKORC1 AA基因型的健康男性志愿者单独服用5  mg剂量的华法林,同时服用稳态imrecoxib。在整个试验中,单独使用华法林和同时使用imrecoxib都具有安全性和良好的耐受性。华法林和imrecoxib共同给药后,华法林对映体的Cmax,AUC0-t和t1/2或国际标准化比率 (INR) 的AUC与单独的华法林均无显着差异。INR(AUC) 的几何平均比率 (GMRs) (华法林   + imimrecoxib: 单独使用华法林) 为1 (0.99,1.01)。华法林   + imimrecoxib的华法林AUC0-∞ (90% 置信区间,CIs) 的GMRs: R-华法林单独1.12 (1.08,1.16),S-华法林1.13 (1.07,1.18)。AUC0-∞ 、Cmax和INR (AUC) 的GMRs的90% CIs均在0.8-1.25区间内。华法林和伊瑞昔布的组合不会影响单剂量华法林的药效学和药代动力学; 因此,在用伊瑞昔布和华法林治疗患者时,不需要调整华法林的剂量。

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