Biotransformation and pharmacokinetics of the nitrate trans-2-amino-2-methyl-N-(4-nitroxycyclohexyl)-propionamide in dogs

• Published in: Arzneimittel-Forschung Vol. 42; no. 11; p. 1306
• Main Authors: Pressmar, F, Neidlein, R, Strein, K
• Format: Journal Article
• Language: English
• Published: Germany 01.11.1992
• Subjects: Amides - metabolism; Amides - pharmacokinetics; Amides - urine; Animals; Biotransformation; Blood Proteins - metabolism; Cyclohexylamines - metabolism; Cyclohexylamines - pharmacokinetics; Cyclohexylamines - urine; Dogs; Feces - chemistry; Female; Gas Chromatography-Mass Spectrometry; Half-Life; Magnetic Resonance Spectroscopy; Male; Protein Binding
• ISSN: 0004-4172

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.