Türck D, Su C A, Heinzel G, Busch U, Bluhmki E, Hoffmann J
Department of Pharmacokinetics and Drug Metabolism, Biberach an der Riss, Germany.
Eur J Clin Pharmacol. 1997;51(5):421-5. doi: 10.1007/s002280050224.
The effect of multiple oral doses of meloxicam 15 mg on the pharmacodynamics and pharmacokinetics of warfarin was investigated in healthy male volunteers. Warfarin was administered in an individualized dose to achieve a stable reduction in prothrombin times calculated as International Normalized Ratio (INR) values. Then INR- and a drug concentration-time profile was determined. For the interaction phase, meloxicam was added for 7 days and then INR measurements and the warfarin drug profiles were repeated for comparison. Overall, warfarin treatment lasted for 30 days.
Warfarin and meloxicam were well tolerated by healthy volunteers in this study. Thirteen healthy volunteers with stable INR values entered the interaction phase. Prothrombin times, expressed as mean INR values, were not significantly altered by concomitant meloxicam treatment, being 1.20 for warfarin alone and 1.27 for warfarin with meloxicam cotreatment. R- and S-warfarin pharmacokinetics were similar for both treatments. Geometric mean (% gCV) AUCss values for the more potent S-enantiomer were 5.07 mg.h.l-1 (27.5%) for warfarin alone and 5.64 mg.h.l-1 (28.1%) during the interaction phase. Respective AUCss values for R-warfarin were 7.31 mg.h.l-1 (43.8%) and 7.58 mg.h.l-1 (39.1%).
The concomitant administration of the new non-steroidal anti-inflammatory drug (NSAID) meloxicam affected neither the pharmacodynamics nor the pharmacokinetics of a titrated warfarin dose. A combination of both drugs should nevertheless be avoided and, if necessary, INR monitoring is considered mandatory.
在健康男性志愿者中研究多次口服15毫克美洛昔康对华法林药效学和药代动力学的影响。华法林采用个体化剂量给药，以使根据国际标准化比值（INR）计算的凝血酶原时间稳定降低。然后测定INR和药物浓度-时间曲线。在相互作用阶段，添加美洛昔康7天，然后重复进行INR测量和华法林药物曲线以作比较。总体而言，华法林治疗持续30天。
在本研究中，健康志愿者对华法林和美洛昔康耐受性良好。13名INR值稳定的健康志愿者进入相互作用阶段。以平均INR值表示的凝血酶原时间，在联合使用美洛昔康治疗时无显著改变，单独使用华法林时为1.20，联合使用美洛昔康时为1.27。两种治疗的R-和S-华法林药代动力学相似。更具活性的S-对映体的几何平均（%gCV）稳态血药浓度-时间曲线下面积（AUCss）值，单独使用华法林时为5.07毫克·小时·升⁻¹（27.5%），在相互作用阶段为5.64毫克·小时·升⁻¹（28.1%）。R-华法林的相应AUCss值分别为7.31毫克·小时·升⁻¹（43.8%）和7.58毫克·小时·升⁻¹（39.1%）。
新的非甾体抗炎药（NSAID）美洛昔康与滴定剂量的华法林联合使用，既不影响药效学，也不影响药代动力学。然而，两种药物仍应避免联合使用，如有必要，INR监测被认为是必需的。
