Davi H, Carayon A, Berthet D, Cautreels W, Dommisse R, Zannad M D
Biomed Environ Mass Spectrom. 1986 Oct;13(10):559-68. doi: 10.1002/bms.1200131008.
[14C]-Penticainide, 2-[2-(diisopropylamino) ethyl]-4-methyl-2-(2-pyridyl)pentanamide, a new antiarrhythmic agent, was administered as a single oral dose to rats, dogs, baboons (30 mg kg-1) and to healthy, informed volunteers (300 mg). Excretion of radioactivity was followed for 3 days in urine and faeces. In man, about 95% of the administered radioactivity was eliminated in the urine and levels ranging from 56 to 86% were observed in animals. The radioactivity that did not appear in the urine was almost quantitatively recovered in the faeces. Metabolites in urine were isolated by thin-layer chromatography and identified by mass spectrometry and nuclear magnetic resonance. In addition to the unchanged drug, nine metabolites and an artifact compound resulting from the partial degradation of one metabolite, were identified among the thirteen radioactive compounds detected. The major metabolites resulted from N-dealkylation of the diisopropyl moiety, oxidation of the isobutyl side-chain and hydrolytic cleavage of the amide. Comparison of the excretion and metabolic patterns of animals with those of man revealed that the dog should be a most suitable model for predicting the pharmacological and toxicological effects of penticainide in man.
新型抗心律失常药物[14C]喷替卡胺（2-[2-(二异丙基氨基)乙基]-4-甲基-2-(2-吡啶基)戊酰胺）以单次口服剂量给予大鼠、狗、狒狒（30毫克/千克）和健康且知情的志愿者（300毫克）。在3天内跟踪尿液和粪便中的放射性排泄情况。在人体中，约95%的给药放射性通过尿液排出，在动物中观察到的排出水平为56%至86%。未出现在尿液中的放射性几乎在粪便中全部回收。尿液中的代谢产物通过薄层色谱法分离，并通过质谱和核磁共振进行鉴定。在检测到的13种放射性化合物中，除了未变化的药物外，还鉴定出9种代谢产物和一种由一种代谢产物部分降解产生的假象化合物。主要代谢产物是由二异丙基部分的N-脱烷基化、异丁基侧链的氧化和酰胺的水解裂解产生的。将动物与人体的排泄和代谢模式进行比较后发现，狗应该是预测喷替卡胺对人体药理和毒理作用的最合适模型。
