双氢可待因的:一个新的阿片类药物基质多态CYP2D6的人类。

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弗洛姆MF,霍夫曼U, Griese欧盟Mikus G

双氢可待因的:一个新的阿片类药物基质多态CYP2D6的人类。

中国新药杂志。1995年10月,58 (4):374 - 82。0009 - 9236 . doi: 10.1016 / (95) 90049 - 7。

PubMed ID

7586928 (在PubMed

]

文摘

背景:阿片类双氢可待因(DHC)是常用的作为镇痛药和止咳药的代理。然而,直到现在没有详细的数据在人类双氢可待因的新陈代谢。因此我们研究途径,有助于消除双氢可待因,我们测试的假设双氢可待因O-demethylation, dihydromorphine CYP2D6多态(DHM)是催化。方法:单剂量的双氢可待因口服接种6广泛(代谢率(先生)< = 1),两个中间(1 <,< 20)和六个可怜的代谢(> = 20)先生的金雀花碱/ debrisoquin。血清浓度的双氢可待因和dihydromorphine测量多达25小时,尿排泄的共轭和非结合的双氢可待因,dihydromorphine, nordihydrocodeine被确定。结果:没有药物动力学的差异双氢可待因的广泛和穷人之间的代谢。然而,血清浓度时间曲线下的面积(AUC),部分代谢间隙,和总尿复苏dihydromorphine显著降低贫困的代谢(10.3 + / - 6.1 nmol.hr / L;7.0 + / - 4.1毫升/分钟;1.3% + / - 0.9%的剂量)而广泛的代谢(75.5 + / - 42.9 nmol.hr / L;49.7 + / - 29.9毫升/分钟; 8.9% +/- 6.2%; p < 0.01). There was a strong correlation between the AUCDHC/AUCDHM ratio and the urinary metabolic ratio of sparteine (rS = 0.89, p = 0.001). No significant differences between extensive and poor metabolizers were detected in urine for conjugated dihydrocodeine (extensive metabolizers, 27.7% of dose; poor metabolizers, 31.5%), unconjugated dihydrocodeine (extensive metabolizers, 31.1%; poor metabolizers, 31.1%), conjugated nordihydrocodeine (extensive metabolizers, 6.3%; poor metabolizers, 5.4%), or unconjugated nordihydrocodeine (extensive metabolizers, 15.8%; poor metabolizers, 19.5%). CONCLUSIONS: Dihydrocodeine O-demethylation to dihydromorphine is impaired in poor metabolizers of sparteine. The main urinary metabolites after administration of dihydrocodeine are the parent compound and its conjugates in extensive and poor metabolizers.

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药物酶

药物	酶	类	生物	药理作用	行动
双氢可待因的	细胞色素P450 2 d6	蛋白质	人类	未知的	底物	细节