Pharmacokinetics of the organic nitrates trans-N-(4-nitroxycyclohexyl)-urea in dogs and trans-N-(4-nitroxycyclohexyl)-acetamide in dogs and in man.
The pharmacokinetic behavior of the organic nitrates BM 12.1247 (trans-N-(4-nitroxycyclohexyl)-urea) and BM 12.1307 (trans-N-(4-nitroxycyclohexyl)-acetamide, CAS 137291-91-3) were examined in beagle dogs after oral and intravenous administration. To this end, a reliable and specific assay using capillary gaschromatography with electron capture detection (GC-ECD) was developed. BM 12.1247 showed its maximum plasma level 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-life after i.v. administration, concerning BM 12.1307, the elimination half-lives were still longer, they reached 11-13 h and bioavailability reached 68-70%; these results were confirmed by crossover tests. In a first application of healthy volunteers it was possible to show that the organic nitrate BM 12.1307 is eliminated much more slowly in man than in dog, the half-life of the compound in man being longer than the half-life in dog by a factor of 2.3.
Pharmaceutical-Chemical Institute, University of Heidelberg, Fed. Rep. of Germany.
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C
Zell
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Neidlein
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K
Strein
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Bartsch
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Michel
D000081:Acetamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009574:Nitro Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013045:Species Specificity; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000081:Acetamides; C090716:BM 12.1307; C091834:N-(4-nitroxycyclohexyl)urea; D009566:Nitrates; D009574:Nitro Compounds; D014665:Vasodilator Agents; D014508:Urea