The urinary metabolites of p-phenoxyphenol methanesulfonate ( I ) in rat and man were characterired. The drug was extensively nietabolired in both cpecies and excreted mainly in the form of conjugated phenolic compounds. The major metabolite of I in both species was identified as the conjugated monohydroxylated compound, p-(4-hydroxqphenoxy)phenol rnethanesulfonate (11). Threc minor metabolite\ were also characterized and tentatively identified as: (11) a dihydroxylated derivative, probably p-(3.4-dihydroxyp1ienoxq)plienol methanesulfonate (111); ( h ) a hydroxy and mcthoxy derivative. probably p-(4-hydroxy-3-methoxyphenoxy)phenol mcthanesulfonate (IV): and (c) a dihydroxy and methoxy derivative (V). The exact positions of the aromatic substituents in these three compounds were not rigorously established. Cornpounds I1 and 1V were found in hoth free and conjugated forms, but Compounds 111 and V were found in the conjugated form only. Qualitatively, the metabolites of I found in rat and human urine were similar. The hypolipidemic activity of 11 was equivalent to that of the parent compound.
Keyphrases n p-Phenoxyphenol methanesulfonate-identi~eation of urinary metabolites. rat, man 0 Urinary metabolites-pphenoxyphenol methaneculfonate, rat. man p-Phenoxyphenol methanesulfonateL (I, ClrH120 S, mol. wt. 264) has beet1 shown to be a n active hypocholestcrolcmic agent in both surfactant?-treated and dietary cholesterol and cholic acid-fed rats. Its pharmacological properties were reported previously (I). To study the absorption, metabolism, and excretion of this compound in animalsand man. a GLC method for measuring the intact drug was developed. Little. if any, unchanged drug was found in the urine of I-treated rats. Analysis of thc urine specimens, using TLC techniques, indicated that the compound was metabolized to several products. Therefore, studies were initiated to: (a) identify the major urinary metabolites of this compound in rats and man, and (11) determine the biological activities of the major metabolites in rat and man. * 'Iriton. oxyethylared tertiary octylphenol forrnaldchydc polymer.