Metabolism of Drugs. LXIV. Species Differences of Metabolism of Phenacetylurea

In our previous papers, it was shown that phenacetylurea administered to rabbits is metabolized to 3-methoxy-4-hydroxyphenacetylurea, but in mice it is not converted to this unique metabolite. The present study revealed that the above metabolite is also excreted as one of the major metabolites in the urine of guinea pigs and a human after doses of phenacetylurea, as well as rabbits, whereas rats apparently do not follow to this pathway. Although in these species of animals and in a human the metabolic patterns of phenacetylurea were somewhat different each other, the drug was metabolized by two main pathways, hydroxylation of aromatic ring and hydrolysis of ureide group in all species examined. The identification and determination of the metabolites in animal species were facilitated by use of 14C-labeled phenacetylurea.