Chan R L, Chaplin M D
Drug Metab Dispos. 1985 Sep-Oct;13(5):566-71.
Nafarelin acetate (less than Glu-His-Trp-Ser-Tyr-3-(2-naphthyl)-D-Ala-Leu-Arg-Pro-Gly-NH2) is a potent agonistic analogue of luteinizing hormone-releasing hormone. After a single iv administration of nafarelin acetate (with 14C label at C-3 of 3-(2-naphthyl)-D-Ala) to female rhesus monkeys, about 80% of the radioactivity was eliminated in urine. Five major radioactive urinary metabolites were isolated and purified by reversed phase HPLC. Four of these metabolites, identified by amino acid analysis, were short peptides: the 5-10-hexapeptide amide, the 6-10-pentapeptide amide, the 5-7-tripeptide, and the 6-7-dipeptide. The fifth metabolite, which accounted for about 15% of the radioactivity administered, was shown by NMR and mass spectrometry to be 2-naphthylacetic acid. A possible pathway of its formation is by oxidative deamination of 3-(2-napthyl)-D-Ala to give the corresponding alpha-keto acid, followed by oxidative decarboxylation of the alpha-keto acid. These five metabolites together accounted for about 70% of the radioactivity recovered in the urine of rhesus monkeys, or more than half of the radioactivity in the administered dose. A minor metabolite, which was not isolated, coeluted with 3-(2-naphthyl)-D-Ala in two solvent systems on HPLC. Nafarelin acetate was also present in small amounts. Several of these metabolites were also present in plasma of the rhesus monkey.
醋酸奈法瑞林（少于谷氨酸-组氨酸-色氨酸-丝氨酸-酪氨酸-3-(2-萘基)-D-丙氨酸-亮氨酸-精氨酸-脯氨酸-甘氨酰胺）是促黄体生成素释放激素的一种强效激动剂类似物。对雌性恒河猴单次静脉注射醋酸奈法瑞林（3-(2-萘基)-D-丙氨酸的C-3位带有14C标记）后，约80%的放射性物质经尿液排出。通过反相高效液相色谱法分离并纯化出了五种主要的放射性尿液代谢物。经氨基酸分析鉴定，其中四种代谢物为短肽：5-10六肽酰胺、6-10五肽酰胺、5-7三肽和6-7二肽。第五种代谢物占给药放射性的约15%，经核磁共振和质谱分析表明为2-萘乙酸。其形成的可能途径是3-(2-萘基)-D-丙氨酸氧化脱氨生成相应的α-酮酸，随后α-酮酸氧化脱羧。这五种代谢物共同占恒河猴尿液中回收放射性的约70%，即给药剂量中放射性的一半以上。一种未分离出的次要代谢物在高效液相色谱的两种溶剂系统中与3-(2-萘基)-D-丙氨酸共洗脱。醋酸奈法瑞林也有少量存在。这些代谢物中的几种也存在于恒河猴的血浆中。
