吗啡与双氯芬酸的体内相互作用

Yoshiaki Kimura, Koki Muryoi, Mika Shibata, N. Ozaki, K. Arai
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引用次数: 3

摘要

阿片类镇痛药和非甾体抗炎药(NSAIDs)之间可能的药代动力学相互作用的研究数量有限,非甾体抗炎药(NSAIDs)通常用于联合治疗慢性疼痛。在大鼠体内,吗啡的主要代谢途径是通过udp -葡萄糖醛酸转移酶葡萄糖醛酸化成吗啡-3-葡萄糖醛酸盐(M3G)。在这项研究中,我们研究了双氯芬酸(NSAID)对体外大鼠肝组织匀浆形成M3G的影响。双氯芬酸竞争性抑制M3G的形成,平均Ki为19.9 μM。由于这些体外研究结果表明,药代动力学相互作用发生在体外,我们研究了双氯芬酸是否抑制吗啡在大鼠体内的葡萄糖醛酸化。单剂量双氯芬酸增加吗啡和M3G的血清浓度,并在Von Frey试验中显示出更高的镇痛效果。此外,双氯芬酸引起吗啡尿浓度的净下降,但M3G通过胆道和尿路的排泄没有变化。这些结果表明,与体外数据相反,单剂量双氯芬酸不会改变体外吗啡的葡萄糖醛酸化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In Vivo Interaction of Morphine and Diclofenac
The number of studies on possible pharmacokinetic interactions between opioid analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs), which are commonly used in combination for the treatment of chronic pain, is limited. In rats, the major metabolic pathway of morphine is glucuronidation to morphine-3-glucuronide (M3G) by UDP-glucuronosyltransferase. In this study, we investigated the influence of diclofenac (NSAID) on the formation of M3G in vitro using rat liver tissue homogenates. Competitive inhibition of M3G formation by diclofenac was observed with an average Ki of 19.9 μM. Because these in vitro findings suggested that a pharmacokinetic interaction occurs in vitro , we investigated whether diclofenac inhibits the glucuronidation of morphine in rats. A single dose of diclofenac increased serum concentrations of both morphine and M3G and showed a higher analgesic efficacy in the Von Frey test. Furthermore, diclofenac caused a net decrease in morphine urine concentrations, but the excretion of M3G through biliary and urinary routes was unchanged. These results demonstrated that in contrast to in vitro data a single dose of diclofenac did not alter the glucuronidation of morphine in vitro .
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