影响tolterodine CYP2D6 * 10基因型的药物动力学。

文章的细节

引用

复制到剪贴板

Oishi M,千叶K, Malhotra B,诹访元T

影响tolterodine CYP2D6 * 10基因型的药物动力学。

药物金属底座Dispos。2010年9月,38 (9):1456 - 63。doi: 10.1124 / dmd.110.033407。Epub 2010年6月7日。

PubMed ID

20530222 (在PubMed

]

文摘

这个研究调查的影响减少功能等位基因CYP2D6 * 10,可一个中间代谢的原因(IM),在tolterodine药物动力学。Tolterodine主要代谢活跃5-hydroxymethyl代谢物(5-HM)由CYP2D6 5-HM也是由CYP2D6代谢。亚洲和白人健康志愿者(n = 108)每天一次收到多个剂量tolterodine, tolterodine的血清浓度和5-HM测量。所有受试者对CYP2D6基因分型。Tolterodine曝光(曲线下的面积(AUC)]为了增加CYP2D6 * 1 / * 1(广泛的代谢(EM)] < CYP2D6 * 1 / * 10 < CYP2D6 * < CYP2D6 10 / * 10 * 5 / * 10。是预期的顺序5-HM接触将被逆转。然而,5-HM AUC tolterodine增加相同的顺序。这一现象被解释为考虑生产和消除5-HM CYP2D6中介。tolterodine和5-HM曝光CYP2D6 * 10 / * 10在统计学上高于CYP2D6 * 1 / * 1(分别为3和1.5倍)。CYP2D6 * 4 / * 4(可怜的代谢(PM)], 5-HM不是生产和tolterodine暴露是20倍高于CYP2D6 * 1 / * 1。 With consideration for higher protein binding of tolterodine than 5-HM, the exposure as a sum of the unbound fraction of tolterodine and 5-HM (active moiety) in CYP2D6*10/*10 was 1.8-fold higher than that in CYP2D6*1/*1 and was also higher than that in CYP2D6*4/*4. Simulation using the values of EM and PM demonstrated that the maximum possible active moiety exposure was around the observed values of CYP2D6*5/*10, which were 1.9-fold higher than those for CYP2D6*1/*1. This is the first report to provide an example in which the IM shows higher exposure to pharmacological active moiety than the EM and PM.

beplay体育安全吗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
Tolterodine	细胞色素P450 2 d6	蛋白质	人类	未知的	底物	细节