Venkataramanan R, Abbott F S, Axelson J E
J Pharm Sci. 1982 May;71(5):491-4. doi: 10.1002/jps.2600710504.
The metabolism of tocainide, an oral antiarrhythmic agent, was studied in male Wistar rats following oral administration of 15 mg/kg of tocainide hydrochloride. Qualitative and quantitative identification of the metabolites in urine was carried out by GC-mass spectrometry and electron capture detector gas chromatography. About 15-20% of the dose administered was excreted as intact drug in the urine. An additional 20% of the dose was present as acid hydrolysable conjugates. Enzymatic hydrolysis (beta-glucuronidase) revealed half of the acid hydrolysable conjugates to be a glucuronide. The enzyme mediated hydrolysis was blocked by its specific inhibitor saccharo-1,4-lactone. N-acetyl tocainide, an oxidatively deaminated tocainide, an aldehyde adduct of tocainide, and a cyclic hydantoin derivative of tocainide were also identified as metabolites in the urine samples.
在雄性Wistar大鼠口服15 mg/kg盐酸妥卡尼后，对口服抗心律失常药妥卡尼的代谢情况进行了研究。通过气相色谱 - 质谱联用仪和电子捕获检测器气相色谱法对尿液中的代谢物进行定性和定量鉴定。给药剂量的约15 - 20%以原形药物经尿液排出。另外20%的剂量以可酸水解的缀合物形式存在。酶促水解（β - 葡萄糖醛酸酶）显示，可酸水解缀合物的一半是葡萄糖醛酸苷。该酶介导的水解被其特异性抑制剂糖 - 1,4 - 内酯阻断。N - 乙酰妥卡尼、氧化脱氨基的妥卡尼、妥卡尼的醛加合物以及妥卡尼的环状乙内酰脲衍生物也被鉴定为尿液样本中的代谢物。
