ISOLATION AND IDENTIFICATION OF SOME METABOLITES OF PHENYRAMIDOL (CABRAL) FROM HUMAN URINE

Abstract

The biological transformation of phenyramidol (I) some of which is also excreted unchanged, occurs by 3 main degradative pathways: hydroxylation of the pyridine ring in position 3 (metabolite V) and 5 (metabolite VI); cleavage of the ethanolamine chain with the formation of 2-aminopyridine (metabolite II) and presumably mandelic aldehyde; and conjugation with glucuronic acid (metabolite III). Secondary reactions result in the production of benzoyl carbinol (metabolite XV), benzoic acid (metabolite XI), mandelic acid (metabolite XII) and the glucuronides of V, VI, VII, XII and possibly II (metabolites VIII, IX, X, XIII and IV), all of which were also found as free, unconjugated compounds. A further, unusual reaction is the dimerization of metabolite VI with the formation of a dipyridyl derivative (metabolite VII), which is excreted partly as the free compound, but mainly as the glucuronide (metabolite X). The occurrence of 2-(N-benzylamino)-pyridine (XIV) in the urine could not be explained. Four further excretory products (metabolites XVI, XVII, XVIII and XIX) were not identified; XVI and XVII were extracted at an alkaline pH; XVIII and XIX were extracted under neutral conditions. They could be detected both as free compounds, and after hydrolysis with HCl or alkali, but not after treatment with .beta.-glucuronidase.