口头的新陈代谢和性格dipeptidyl peptidase-4抑制剂,linagliptin,人类。
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薄板,Ludwig-Schwellinger E, Grafe-Mody欧盟,Withopf B,瓦格纳K
口头的新陈代谢和性格dipeptidyl peptidase-4抑制剂,linagliptin,人类。
药物金属底座Dispos。2010年4月,38 (4):667 - 78。doi: 10.1124 / dmd.109.031476。2010年1月19日Epub。
- PubMed ID
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20086031 (在PubMed]
- 文摘
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的药物动力学和代谢linagliptin (BI1356 8 - (3 r-amino-piperidin-1-yl) 7-but-2-ynyl-3-methyl-1 (4-methyl-quinazolin-2-ylmeth yl) 3, 7-dihydro-purine-2, 6-dione)健康志愿者进行调查。10 - 5毫克(14)C-labeled药物口服或静脉注射,分别。粪便排泄的主要排泄途径为84.7%(订单)和58.2%(注射)的剂量。肾排泄占5.4%(订单)和30.8%(注射)的剂量。不变linagliptin是最丰富的放射性核素在所有矩阵进行调查。曝光(曲线下的面积0-24 h)等离子体的母体化合物占191海里。h(订单)和356海里。分别h(注射)。的主要代谢物7-but-2-ynyl-8 - (3 s-hydroxy-piperidin-1-yl) 3-methyl-1 (4-methyl-quinazolin-2-ylme肌酸)3,7-dihydro-purine-2, 6-dione观察(CD1790) > 10%的母体化合物系统性暴露后口服。linagliptin的代谢物被确认为S-3-hydroxypiperidinly导数。 Experiments that included stable-labeled isotope techniques indicated that CD1790 was formed by a two-step mechanism via the ketone 7-but-2-yn-1-yl-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]-8-(3-oxopiperidin-1- yl)-3,7-dihydro-1H-purine-2,6-dione (CD10604). The initial ketone formation was CYP3A4-dependent and rate-limiting for the overall reaction to CD1790. Aldo-keto reductases with minor contribution of carbonyl reductases were involved in the subsequent stereoselective reduction of CD10604 to CD1790. The antipodes of linagliptin and CD1790 were not observed with adequate enantioselective liquid chromatography-tandem mass spectrometry methods. Other minor metabolites were identified by mass spectrometry and NMR investigations. However, it was concluded that the metabolites of linagliptin only play a minor role in the overall disposition and elimination of linagliptin.
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药物 酶 类 生物 药理作用 行动 Linagliptin 细胞色素P450 3 a4 蛋白质 人类 未知的底物抑制剂细节 - 药物反应
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反应 细节 细节 细节 细节 细节
