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

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...

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Published inArzneimittel-Forschung Vol. 42; no. 10; p. 1186
Main Authors Pressmar, F, Neidlein, R, Strein, K, Bartsch, W
Format Journal Article
LanguageEnglish
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
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Summary: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.
ISSN:0004-4172