BM-121307

The biotransformation of BM 12.1307 (trans-N-(4-nitroxycyclohexyl)acetamide, CAS 137213-91-3) in the dog was examined after oral and i.v. administration.For that purpose, the organic nitrate was synthesized as radioactive [¹⁴C]- and as [¹³C]-labeled compoundsThe defined isotopic mixture was administered to the dogs.Within the examined period of 168 h, the elimination of BM 12.1307 and its metabolites via urine and feces amounted to 76.5% after oral application and to 80.7% of the applied dose after i.v. application.The major amount of radioactivity was eliminated via urine (69.4% and 73.6% of the dose, resp.), whereas the fecal elimination was found to be negligible.Investigations of the urinary samples showed that the drug is metabolized to a high percentage.Trans-N-(4-Hydroxycyclohexyl)acetamide is the main metabolite; 73% of the radioactive compounds (after p.o.-administration and 69% after i.v. application) could be identified as the alc. of BM 12.1307; the amounts of the drug totalled 9% and 13%, resp.The quant. determination of BM 12.1307 in urine and plasma was performed by gas chromatog.; the amount of the main metabolite excreted in urine was determined by high-pressure liquid chromatog.Trans-N-(4-hydroxycyclohexyl)-acetamide, N-(4-oxocyclohexyl)acetamide, and 3-acetamido-7-oxa-bicyclo[4.1.0]heptane were formed as metabolites.For the identification and characterization of the possible metabolic structures, these compounds were synthesized and used in comparison with the detected drugs.