[Metabolic degradation of clonidine (author's transl)]

Abstract

From the urine of dogs treated with 14C-clonidine (Catapres) 6 radioactive substances were isolated and their chemical structures identified. The presence of unchanged clonidine, p-hydroxy-clonidine, and dichlorophenylguanidine was confirmed and three new metabolites were detected: 1-(2,6-dichloro-4-hydroxyphenyl)-guanidine; 2-[(2,6-dichlorophenyl)-imino-a1-imidazolidine-4-one; 2-[2,6-dichloro-4-hydroxyphenyl)-imino]-imidazolidine-4-one. The splitting of the imidazolidine ring and the hydroxylation of the phenyl ring are the two principal routes of metabolism. A comparison of the metabolic patterns in the urines of dog, rat, and man showed that the 6 identified compounds were eliminated by all three specieis, the relative amounts, hoever, were different. Man eliminated clonidine mainly in the unchanged form; the dog metabolized the compound most readily of the 3 species investigated.