在美沙酮抑制CYP2D6-mediated曲马朵O-demethylation但不是丁丙诺啡维护病人。

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科勒JK, Michalakas JR,詹姆斯嗯,Farquharson, Colvill J,白色的JM,索莫吉氏AA

在美沙酮抑制CYP2D6-mediated曲马朵O-demethylation但不是丁丙诺啡维护病人。

Br中国新药杂志。2012年11月,74 (5):835 - 41。doi: 10.1111 / j.1365-2125.2012.04256.x。

PubMed ID

22369095 (在PubMed

]

文摘

什么是已经知道这个主题:管理疼痛的阿片类药物依赖个人问题是由于许多问题包括阿片类药物交叉抗性。因此需要找到替代止痛剂对于古典阿片类药物和曲马多可能是其中一个选择。美沙酮抑制CYP2D6体内和体外。我们旨在调查美沙酮曲马多的途径代谢的影响:O-demethylation (CYP2D6) opioid-active代谢物M1和酶(CYP3A4)去M2在在美沙酮和丁丙诺啡科目维护控制。这个研究补充道:丁丙诺啡,受试者相比,美沙酮减少了曲马多的间隙主动O-desmethyl-tramadol (M1),但没有影响N-desmethyltramadol (M2)的形成。类似于其他镇痛药的活性代谢物形成的CYP2D6如可待因、减少形成O-desmethyltramadol (M1)可能会导致降低了受试者对美沙酮维持镇痛。因此替代止痛药CYP2D6的新陈代谢是独立应该利用这个病人的人口。目的:比较O - (CYP2D6介导)和N - (CYP3A4介导)脱甲基代谢之间的曲马朵美沙酮和丁丙诺啡CYP2D6保持广泛的代谢。方法九七美沙酮和丁丙诺啡维护受试者收到一个100毫克剂量的盐酸曲马多。血液收集4 h和化验曲马多、美沙酮、丁丙诺啡和norbuprenorphine(在适当的地方)和所有4小时尿化验了曲马多和M1和M2代谢物。 RESULTS: The urinary metabolic ratio [median (range)] for O-demethylation (M1) was significantly lower (P= 0.0002, probability score 1.0) in the subjects taking methadone [0.071 (0.012-0.103)] compared with those taking buprenorphine [0.192 (0.108-0.392)], but there was no significant difference (P= 0.21, probability score 0.69) in N-demethylation (M2). The percentage of dose [median (range)] recovered as M1 was significantly lower in subjects taking methadone compared with buprenorphine (0.069 (0.044-0.093) and 0.126 (0.069-0.187), respectively, P= 0.04, probability score 0.19), M2 was significantly higher in subjects taking methadone compared with buprenorphine (0.048 (0.033-0.085) and 0.033 (0.014-0.049), respectively, P= 0.04, probability score 0.81). Tramadol was similar (0.901 (0.635-1.30) and 0.685 (0.347-1.04), respectively, P= 0.35, probability score 0.65). CONCLUSIONS: Methadone inhibited the CYP2D6-mediated metabolism of tramadol to M1. Hence, as the degree of opioid analgesia is largely dependent on M1 formation, methadone maintenance patients may not receive adequate analgesia from oral tramadol.

DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
美沙酮	细胞色素P450 2 d6	蛋白质	人类	没有	底物 抑制剂	细节