F. Sun, J. Stafford
Apr 1, 1974
Citations
0
Influential Citations
4
Citations
Quality indicators
Journal
Journal of pharmaceutical sciences
Abstract
The patterns of urinary excretion products of N,N-dimethyl-N′-(p-phenoxyphenyl)sulfamide (I) in the rat, dog, and human have been examined. After oral administration, the drug was extensively metabolized in all species and the amount of intact drug excreted in the urine was negligible (<1%). The metabolic pathways were via hydroxylation of the phenoxy ring, N-demethylation, O-methylation, and conjugation. The following metabolites have been identified in free and/or conjugated form: N-methyl-N′-(p-phenoxyphenyl)sulfamide (II), N,N-dimethyl-N′-p-(4-hydroxyphenoxy)phenylsulfamide (III), N,N-dimethyl-N′-p-(2-hydroxyphenoxy)phenylsulfamide (IV), N-methyl-N′-p-(4-hydroxyphenoxy)phenylsulfamide (V), N-methyl-N′-p-(2-hydroxyphenoxy)phenylsulfamide (VI), N,N-dimethyl-N-p-(4-hydroxy-3-methoxyphenoxy)phenylsulfamide (VII), and N-methyl-N′-p-(4-hydroxy-3-methoxyphenoxy)phenylsulfamide (VIII). The major differences in the patterns of urinary metabolites were: (a) the monomethyl (II) was the major metabolite in the dog and human but a minor one in the rat, (b) the para-hydroxylated compound (III) was the major metabolite in the rat, (c) hydroxylation of the phenoxy ring in the ortho-position (IV and VI) was observed in the rat and dog but not in the human, and (d) the methoxylated compound (VII) was found only in rat urine.