Pressmar F, Neidlein R, Strein K
Pharmaceutical-Chemical Institute, University of Heidelberg, Fed. Rep. of Germany.
Arzneimittelforschung. 1992 Nov;42(11):1306-11.
The biotransformation and the pharmacokinetic behavior of the organic nitrate trans-2-Amino-2-methyl-N-(4-nitroxycyclohexyl)-propionamide (BM 12.1179, CAS 129795-96-6) were examined in dogs. BM 12.1179 was predominantly eliminated by urinary excretion, and the unchanged molecule prevailed in urine as well as in plasma. By means of various mass spectroscopic methods, the chemical structures of the metabolites were elucidated. As metabolites trans-2-amino-2-methyl-N-(4-hydroxycyclohexyl)-propionamide and trans-2-amino-2-methyl-N-(4-oxocyclohexyl)-propionamide were formed. Urine levels of the main metabolite were determined by high-pressure liquid chromatography; plasma and urine levels of BM 12.1179 were determined by capillary gas chromatography. The absolute bioavailability of BM 12.1179 was 80-100%. The plasma protein binding was about 34% which is high in comparison to other organic nitrates. BM 12.1179 represents a long-acting organic nitrate in that it shows a slow reductive denitration, and a long elimination half-life of about 10 h.
在犬类动物中研究了有机硝酸盐反式-2-氨基-2-甲基-N-(4-硝氧基环己基)-丙酰胺（BM 12.1179，CAS 129795-96-6）的生物转化及药代动力学行为。BM 12.1179主要通过尿液排泄消除，尿液和血浆中均以未变化的分子为主。通过各种质谱方法阐明了代谢物的化学结构。代谢物形成了反式-2-氨基-2-甲基-N-(4-羟基环己基)-丙酰胺和反式-2-氨基-2-甲基-N-(4-氧代环己基)-丙酰胺。主要代谢物的尿液水平通过高压液相色谱法测定；BM 12.1179的血浆和尿液水平通过毛细管气相色谱法测定。BM 12.1179的绝对生物利用度为80 - 100%。血浆蛋白结合率约为34%，与其他有机硝酸盐相比偏高。BM 12.1179是一种长效有机硝酸盐，因为它显示出缓慢的还原脱硝作用，消除半衰期约为10小时。
