BIOTRANFORMATION OF THE ORGANIC NITRATE TRANS-N-(4-NITROXYCYCLOHEXYL)ACETAMIDE IN DOGS

The biotransformation of BM 12.1307 (trans-N-(4-nitroxycyclohexyl) ace tamide CAS 137291-91-3) in the dog was examined after oral and intrave nous administration. For that purpose, the organic nitrate was synthes ized as radioactive [C-14]- and as [C-13]-lableed compounds. The defin ed 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 intravenous application. The major amount of radioactivity was eliminated via urine (69.4% and 73.6% of the dose , respectively), whereas the fecal elimination was found to be negligi ble. Investigations of the urinary samples showed that the drug metabo lized to a high percentage. trans-N-(4-Hydroxycyclohexyl) acetamide is the main metabolite; 73% of the radioactive compounds (after p.o.-adm inistration and 69% after intravenous application could be identified as the alcohol of BM 12.1307; the amounts of the drug totalled 9% and 13% respectively. The quantitative determination of BM 12.1307 in urin e and plasma was performed by gas chromatography; the amount of the ma in metabolite excreted in urine was determined by high-pressure liquid chromatography. Trans-N-(4-hydroxycyclohexyl)-acetamide, N-(4-oxo-cyc lohexyl) acetamide, and 3-acetamide-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 an d used in comparison with the detected drugs.