代谢和消除14 c-donepezil在健康志愿者单剂量的研究。
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佩尔多莫坚称CA, Tiseo PJ Friedhoff LT
代谢和消除14 c-donepezil在健康志愿者单剂量的研究。
Br中国新药杂志。1998年11月,46增刊1:19-24。doi: 10.1046 / j.1365-2125.1998.0460s1019.x。
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9839761 (在PubMed]
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目的:本研究的目的是探讨盐酸多奈哌齐的代谢和消除人类,在管理一个5毫克(液体)口服剂量含有未标记的和14 c-labelled多奈哌齐。方法:这是一个非盲、非随机研究在健康男性志愿者(n = 8)。描述多奈哌齐的新陈代谢,消除了通过分析血液、尿液和粪便样本收集药品管理局后10天时间。总辐射每个收集样本化验,整除跨度为从指定和/或混合样本化验多奈哌齐的代谢物的薄层色谱(TLC)。多奈哌齐在等离子体浓度测定高效液相色谱法。结果:复苏的放射性主题样本平均72%的服用剂量。复苏的服用剂量尿(57%)显著高于恢复粪便(15%)。不变多奈哌齐占恢复剂量在每个矩阵的最大组成部分。三个代谢途径确定:(i) O-dealkylation和羟基化代谢产物M1和M2,随后glucuronidation代谢物M11公路和M12;(2)水解代谢物M4;(3)N-oxidation代谢物M6。 In plasma, the parent compound accounted for about 25% of the dose recovered during each sampling period, as well as of the cumulative dose recovered. The recovered residue showed higher levels of the hydroxylated metabolites M1 and M2 than of their glucuronide conjugates M11 and M12, respectively. In urine, the parent compound accounted for 17%, on average, of the dose recovered from each pooled sample, as well as of the total recovered dose. The major metabolite was the hydrolysis product M4, followed by the glucuronidated conjugates M11 and M12. In faeces, the parent compound also predominated, although it accounted for only 1%, of the recovered dose. A large percentage of the radioactivity in faeces consisted of unidentified very polar metabolites, which were retained at the TLC origin. Of the extracted metabolites, the hydroxylation products M1 and M2 were the most abundant, followed by the hydrolysis product M4 and the N-oxidation product M6. CONCLUSIONS: Donepezil is hepatically metabolized and the predominant route for the elimination of both parent drug and its metabolites is renal, as 79% of the recovered dose was found in the urine with the remaining 21% found in the faeces. Moreover, the parent compound, donepezil, is the predominant elimination product in urine. The major metabolites of donepezil include M1 and M2 (via O-dealkylation and hydroxylation), M11 and M12 (via glucuronidation of M1 and M2, respectively), M4 (via hydrolysis) and M6 (via N-oxidation).
