darifenacin的临床药物动力学。

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darifenacin的临床药物动力学。

45 Pharmacokinet。2006; (4): 325 - 50。

PubMed ID

16584282 (在PubMed

]

文摘

Darifenacin氢溴酸盐是一种选择性毒蕈碱的M(3)受体拮抗剂,用于治疗膀胱过动症障碍表示。Darifenacin发现终端消除半衰期较短静脉和速释后口服剂型(3 - 4个小时),但这增加了prolonged-release (PR)配方(14 - 16小时)。从7.5和15毫克的绝对生物利用度darifenacin公关平板电脑估计为15.4%和18.6%,分别。公关的重复每天换一次口服配方,血浆浓度峰值darifenacin实现post-dose约7小时。口服后,darifenacin从胃肠道吸收,很少改变药物(< 2%)粪便中恢复。每日一次的达到稳定状态后6天政府公关的配方。正如所料,血浆浓度峰值的值(C (max))和血浆浓度时间曲线下的面积是剂量依赖,虽然等离子体浓度的增加比例大于剂量的增加由于presystemic饱和的新陈代谢。从静脉注射,它建立了darifenacin具有moderate-to-high肝提取比例,高血浆间隙(36-52 L / h)和体积的分布(165 - 276升)水超过全身。它是高度蛋白结合的(98%),主要是α(1)酸性糖蛋白。Darifenacin受到广泛的肝代谢,改变药物在尿液和粪便排泄的3%。 Metabolism is mediated by hepatic cytochrome P450 2D6 and 3A4, the main metabolic routes being monohydroxylation in the dihydrobenzfuran ring, dihydrobenzfuran ring opening, and N-dealkylation of the pyrrolidine nitrogen. Several possibly important drug-drug interactions have been identified with darifenacin, including ketoconazole, erythromycin and fluconazole, each of which increases darifenacin mean C(max) by 9.52-, 2.28- and 1.88-fold, respectively. When given with imipramine, darifenacin causes 1.6-fold higher plasma concentrations of the antidepressant and its major metabolite. Moderate hepatic impairment, but not renal insufficiency, has been shown to increase plasma concentrations of the drug. The pharmacokinetic profile of darifenacin is not affected by food.

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药物酶

药物	酶	类	生物	药理作用	行动
Darifenacin	细胞色素P450 2 d6	蛋白质	人类	未知的	底物 抑制剂	细节
Darifenacin	细胞色素P450 3 a4	蛋白质	人类	未知的	底物	细节