Metabolism of terguride in rats and rabbits

After oral administration of 14C-terguride to rats (0.4mg/kg) and rabbits (1, 100mg/kg), metabolites in biological samples were analyzed by the mean of high performance liquid chromatography. In addition, the main metabolites were isolated from perfusate of rat liver and rabbit urine after high dose administration (100mg/kg). The structural elucidation of the isolated metabolites was carried out by 1H-NMR spectroscopy and mass spectrometry. The results showed as follows : (1) In rats, the amount of unchanged substance accounted for 15% of radioactivity in plasma and the other 5 peaks were also detected 4hr after administration. Excreted amount in urine (0 ?? 24hr) was 16% of the dose and 8 peaks were found. Excreted amount in bile (0 ?? 6hr) was 50% of the dose and 2 main metabolites were found. Unchanged substance was detected slightly in both samples. (2) In rabbits, 8 % of radioactivity in plasma 2hr after administration was unchanged substance and the other 8 peaks were found. Excreted amount in urine(0 ?? 24hr) was 38% of the dose, the unchanged substance was detected slightly and the other 7 peaks were found. (3) Although the metabolism rate in rabbits was faster than that of rats, there was no difference in main metabolic pathway between these two species. (4) From the perfusate of rat liver 2 metabolites were isolated, their chemical structures were proposed as N-mono-deethyl-terguride, is a main metabolite in rats plasma and urine of both animals, and oxidative cleavaged form of indole ring. From the rabbits urine mono-deethylated 2-keto-3-hy droxy-terguride was isolated, and it was a main metabolite in plasma and urine of rabbits. (5) The main metabolic pathway was oxidative N-dealkylation and oxidation of double bonds at C2/C3.