PHARMACOKINETICS OF THE ORGANIC NITRATES TRANS-N-(4-NITROXYCYCLOHEXYL)-UREA IN DOGS AND TRANS-N-(4-NITROXYCYCLOHEXYL)-ACETAMIDE IN DOGS ANDIN MAN

The pharmacokinetic behavior of the organic nitrates BM 12.1247 (trans -N-(4-nitroxycyclohexyl)-urea) and BM 12.1307 (trans-N-(4-nitroxycyclo hexyl)-acetamide, CAS 137291-91-3) were examined in beagle dogs after oral and intravenous administration. To this end, a reliable and speci fic assay using capillary gaschromatography with electron capture dete ction (GC-ECD) was developed. BM 12.1247 showed its maximum plasma lev el after 2.2 h by oral application; the bioavailability was nearly 100 %. The elimination half-life of 8.8 h p.o. Corresponded to the half-li fe after i.v. administration concerning BM 12.1307, the elimination ha lf-lives were still longer; they reached 11-13 h and bioavailability r eached 68-70%; these results were confirmed by cross-over tests. In a first application of healthy volunteers it was possible to show that t he organic nitrate BM 12.1307 is eliminated much more slowly in man th an in dog, the half-life of the compound in man being longer than the half-life in dog by a factor of 2.3.