甲基多巴的临床药物动力学。
文章的细节
-
引用
复制到剪贴板 -
E,古纳尔Rugstad他,汉森T
甲基多巴的临床药物动力学。
Pharmacokinet。1982 May-Jun; 7(3): 221 - 33所示。doi: 10.2165 / 00003088-198207030-00003。
- PubMed ID
-
7047042 (在PubMed]
- 文摘
-
从胃肠道吸收甲基多巴是不完整和变量;后口服生物利用度约为25%(8到62%不等)。达到最大血浆浓度的平均时间(达峰时间)(化学决定)是2小时,当活性药物的最大血浆浓度占50%的放射性,其余部分代表各种代谢物。理化测定甲基多巴表明bi-phasic消除静脉注射和口服后发生的相半衰期0.21小时(范围0.16 - 0.26小时)和测试阶段的1.28小时(范围1.02 - 1.69小时)在正常科目。甲基多巴小于15%的蛋白质绑定,而主要代谢物,最可能的是O-sulphate,蛋白结合的约50%。表观分布容积中部舱约为0.23 l /公斤(范围0.19 - 0.32 l /公斤),和分配的总量(计算Vdarea)约为0.60 l /公斤(范围0.41 - 0.72 l /公斤)在健康志愿者。Acid-labile配合口服后形成。这些acid-labile轭合物,尤其是O-sulphate,很可能形成于肠道细胞,因为它们发现静脉注射后在极少量管理。此外,有一个快速的形成部分静脉注射和口服后身份不明的代谢物。静脉注射后政府最著名的定量的葡糖苷酸代谢物methyldopamine和dihydroxyphenylacetone,但5或6其他代谢物的痕迹也被发现和识别。 These metabolites are probably formed in the liver, but the complete metabolic pattern is still unknown. The renal clearance of methyldopa (95 ml/min/m2) is more than 50% higher than the endogenous creatinine clearance. Renal excretion of some metabolites is slower. Extrarenal elimination accounts for about 50% of the total body clearance of the drug. Renal excretion is very low in patients with renal failure, resulting in accumulation of both active drug and, in particular, its metabolites. There is a marked accumulation of unidentified metabolites in renal failure patients, which possibly explains the strong and prolonged hypotensive action of methyldopa in these patients.
