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 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.
Pressmar
F
F
Pharmaceutical-Chemical Institute, University of Heidelberg, Fed. Rep. of Germany.
Neidlein
R
R
Strein
K
K
Bartsch
W
W
D000284:Administration, Oral; D000577:Amides / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D002849:Chromatography, Gas; D004285:Dogs; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D008251:Macaca; D008297:Male; D009566:Nitrates / Q000493:pharmacokinetics*; D010880:Piperidines / Q000493:pharmacokinetics*; D014665:Vasodilator Agents / Q000493:pharmacokinetics*
D000577:Amides; D009566:Nitrates; D010880:Piperidines; D014665:Vasodilator Agents; C078891:4-(2-nitroxyethyl)piperidine; C078890:BM 12.1200; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate