Kristinsson J, Snorradóttir I, Jóhannsson M
Department of Pharmacology, University of Iceland, Reykjavik.
Pharmacol Toxicol. 1994 Mar;74(3):174-80. doi: 10.1111/j.1600-0773.1994.tb01095.x.
The urinary metabolites of orally administered mebeverine hydrochloride (270 mg) were studied in five healthy volunteers with the aid of gas chromatography/mass spectrometry. Mebeverine, which is an ester of veratric acid and 4-(ethyl-[2-(4-methoxyphenyl)-1-methylethyl]amino)butan-1-ol, was completely hydrolysed to the corresponding acid and alcohol moieties. The acid moiety was subsequently O-demethylated to vanillic acid and isovanillic acid, which in turn were further O-demethylated to protocatechuic acid. The alcohol moiety was O-demethylated to the corresponding phenol 4-(ethyl-[2-(4-hydroxyphenyl)-1-methylethyl]amino)butan-1-ol. In 24 hr, 44% of the dose was accounted for as follows: Veratric acid 32%, vanillic acid 2.7%, isovanillic acid 6.5%, 4-(ethyl-[2-(4-methoxyphenyl)-1-methylethyl]amino)butan-1-ol 0.9% and 4-(ethyl-[2-(4-hydroxyphenyl)-1-methylethyl]amino)butan-1-01 2.1%. Only trace amounts of protocatechuic acid were found in the urine. The results indicated that the metabolites were mostly excreted as conjugates. The total excretion of the acid moiety, unchanged or in the form of metabolites was 97.6%. The corresponding value for the alcohol moiety was 5.5%.
在气相色谱/质谱联用仪的辅助下，对5名健康志愿者口服盐酸美贝维林（270毫克）后的尿液代谢产物进行了研究。美贝维林是藜芦酸与4-（乙基-[2-（4-甲氧基苯基）-1-甲基乙基]氨基）丁-1-醇形成的酯，它完全水解为相应的酸和醇部分。酸部分随后发生O-去甲基化生成香草酸和异香草酸，而这两种酸又进一步发生O-去甲基化生成原儿茶酸。醇部分发生O-去甲基化生成相应的酚4-（乙基-[2-（4-羟基苯基）-1-甲基乙基]氨基）丁-1-醇。在24小时内，44%的剂量分布如下：藜芦酸32%、香草酸2.7%、异香草酸6.5%、4-（乙基-[2-（4-甲氧基苯基）-1-甲基乙基]氨基）丁-1-醇0.9%以及4-（乙基-[2-（4-羟基苯基）-1-甲基乙基]氨基）丁-1-醇2.1%。尿液中仅发现痕量的原儿茶酸。结果表明，代谢产物大多以结合物形式排泄。酸部分未变化或代谢产物形式的总排泄率为97.6%。醇部分的相应值为5.5%。
