Drummer O H, Kourtis S
University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg, Victoria (Australia).
Arzneimittelforschung. 1987 Nov;37(11):1225-8.
The biotransformation of di-acid inhibitors of angiotensin converting enzyme was studied in the urine of rats using gas chromatography/mass spectrometry. It was found that after oral administration (10 mg/kg) of enalapril significant amounts (9.2%) of a hydrolytic metabolite of enalaprilat were excreted in urine which was identified as 2-N-alanyl-4-phenylbutanoic acid. This metabolite was present only in trace concentrations in urine after intravenous administration. This pathway was not present, however, with either ramipril or perindopril suggesting that the amide bond in these newer inhibitors is more resistant to hydrolysis than for enalapril. Glucuronidase hydrolysis of urine obtained from rats dosed with either enalapril, ramipril or perindopril indicated the absence of glucuronidate conjugates of these inhibitors in rat urine.
采用气相色谱/质谱联用技术，对大鼠尿液中血管紧张素转换酶二酸抑制剂的生物转化进行了研究。结果发现，口服依那普利（10mg/kg）后，大量（9.2%）依那普利拉的水解代谢产物以2-N-丙氨酰-4-苯基丁酸的形式经尿液排出。静脉注射后，该代谢产物仅以痕量浓度存在于尿液中。然而，雷米普利和培哚普利均不存在此代谢途径，这表明这些新型抑制剂中的酰胺键比依那普利更耐水解。对给予依那普利、雷米普利或培哚普利的大鼠尿液进行葡萄糖醛酸酶水解，结果表明大鼠尿液中不存在这些抑制剂的葡萄糖醛酸酯缀合物。
