Pharmacokinetics of the organic nitrates trans-2-amino-2-methyl-N-(4- nitroxycyclohexylmethyl)-propionamide in dogs, and of 4-(2-nitroxyethyl)-piperidine in dogs and in monkeys

• Published in: Arzneimittel-Forschung Vol. 42; no. 10; p. 1186
• Main Authors: Pressmar, F, Neidlein, R, Strein, K, Bartsch, W
• Format: Journal Article
• Language: English
• Published: Germany 01.10.1992
• Subjects: Administration, Oral; Amides - pharmacokinetics; Animals; Biological Availability; Chromatography, Gas; Dogs; Female; Half-Life; Injections, Intravenous; Isosorbide Dinitrate - analogs & derivatives; Isosorbide Dinitrate - pharmacokinetics; Macaca; Male; Nitrates - pharmacokinetics; Piperidines - pharmacokinetics; Vasodilator Agents - pharmacokinetics
• ISSN: 0004-4172

The plasma concentrations of the organic nitrates (nitric acid esters) trans-2-amino-2-methyl-N-(4-nitroxycyclohexylmethyl)-propionamide (BM 12.1200) and of 4-(2-nitroxyethyl)-piperidine (BM 12.1173, CAS 129999-77-5) were determined in dog plasma by capillary gas chromatography with electron capture detection (GC-ECD). Intra- and interassay variation coefficients of the gas chromatographic analysis lay between 2.9 and 8.8%; recoveries amounted to 50-62%. Both nitric acid esters were absorbed quickly and attained maximum plasma levels within 1 h. The total bioavailability of BM 12.1200 is > 55%, and that of BM 12.1173 is 63%; their elimination half-lives are, respectively, 4.2 h and 1.3-1.4 h. Thus, BM 12.1173 and the reference substance IS-5-MN (isosorbide-5-mononitrate) show corresponding elimination half-lives. These results regarding the pharmacokinetic parameters of BM 12.1173 were confirmed by cross-over application of BM 12.1173 and IS-5-MN to Macaca Arctoides. In comparison to all species which have been treated with IS-5-MN thus far, the shortest elimination half-life (t1/2 = 0.6 h) is found in monkeys.