Metabolism of pheneturide in the rat and in man.

The biotransformation of pheneturide was studied in humans and in the rat. Human volunteers received a single oral dose of 10 mg/kg of pheneturide and the rats were given repeated doses of 250 mg/kg. Urine from both study groups was extracted with Amberlite XAD-2 and the extracts were separated by preparative HPLC after enzymatic hydrolysis. Five metabolites were isolated in man and their structures were determined using NMR and mass spectrometry. The hydrolysis of the ureide function and the 4-hydroxylation of the benzene ring led to the formation of two major metabolites: 2-(4-hydroxyphenyl)-butyroylurea (37.5%) and 2-phenylbutyric acid (40.6%), and to one minor metabolite: 2-(4-hydroxyphenyl)-butyric acid (11.9%). Seven metabolites were isolated in the rat. The 4-hydroxylation of the benzene ring and the C 3 hydroxylation of the aliphatic chain led to the formation of two major metabolites: 2-(4-hydroxyphenyl)-butyroylurea (70.5%) and 3-hydroxy-2-phenyl-butyroylurea (19.6%), whereas the hydrolysis of the ureide function was less important. Only traces of the parent drug were found in humans as well as in the rat.

Febarbamate: metabolism in man.

The biotransformation of 1-(3-butoxy-2-carbamoyloxypropyl)-5-ethyl-5-phenyl-(1H,3H,5H)-pyrimidine-2,4,6-trione (febarbamate) has been investigated in man. Human volunteers received a single oral dose of 15 mg/kg febarbamate. Twenty two metabolites found in urine were separated and purified by means of an extraction with Amberlite XAD-2 and the high performance liquid chromatography. Their chemical structures were established with the help of mass and NMR spectral data and by comparison with known standards. The oxygen dealkylation, the penultimate hydroxylation of the n-butyl chain with consecutive oxidation to the ketone and C 4 hydroxylation of the benzene ring lead to the formation of four major metabolites: 1-(2-carbamoyloxy-3-hydroxypropyl)-5-ethyl-5-phenyl-(1H,3H,5H)-pyrimidine-2,4, 6-trione (41.4%), 1-[3-(3-hydroxybutoxy)-2-carbamoyloxypropyl]-5-ethyl-5-phenyl-(1H,3H,5H)-pyrimidine-2,4,6-trione (20.2%), 1-[3-(3-oxobutoxy)-2-carbamoyloxypropyl]-5-ethyl-5-phenyl-(1H,3H,5H)-pyrimidine-2,4,6-trione (11.1%) and 1-(2-carbamoyloxy-3-hydroxypropyl)-5-ethyl-5-(4-hydroxyphenyl)-(1H,3H,5H)-pyrimidine-2,4,6-trione (9.2%). Hydrolysis of the carbamoyloxy group was insignificant, the pyrimidine ring opening and the oxidation of the 5-ethyl group were not observed. Only traces of the parent drug were found.

Febarbamate: metabolism in the rat.

The metabolism of 1-(3-butoxy-2-carbamoyloxypropyl)-5-ethyl-5-phenyl-(1H,3H,5H)-pyrimidine-2,4,6- trione (febarbamate) in the rat has been studied after oral administration. Using high performance liquid chromatography, fifteen metabolites were isolated from urine, purified and identified by MS and NMR spectrometry. Febarbamate was extensively metabolized and only traces of the unchanged compound were found. The oxygen dealkylation and the (omega-1)-hydroxylation of n-butyl chain are the predominant pathways of the biotransformation and lead to the formation of two major metabolites: 1-(2-carbamoyloxy-3-hydroxypropyl)-5-ethyl-5-phenyl-(1H,3H,5H)-pyrimidine-2,4,6,-trione and 1-[3-(3-hydroxybutoxy)-2-carbamoyloxypropyl]-5-ethyl-5-phenyl-(1H,3H,5H)-pyrimidine-2,4,6,-trione. Hydrolytic cleavage of the ester function, the pyrimidine ring opening and p-hydroxylation of phenyl ring play a less important role. The stepwise degradation of n-butyl chain was also observed.

Comparative study of two anti-ulcerogenic drugs--glaziovine and sulpiride.

The anti-ulcer effect of glaziovine, a major psychotropic alkaloid isolated from Ocotea glaziovii (Laureaceae) and belonging to a new chemical class, has been studied in different types of experimentally induced ulcers in the guinea-pig and the rat. The effect of glaziovine was compared with that of sulpiride.