Identification and renal excretion of probenecid metabolites in man

Abstract

The metabolic fate of probenecid (p-(dipropylsulfamoyl) benzoic acid) in man has been elucidated by determining the chemical structures of the urinary metabolites and their pattern of excretion. The methodology included mainly the utilization of quantitative thin-layer chromatography and the data was confirmed by GLC-MS. Substantiating our previous findings, in 48 hrs about 40% of the dose is eliminated as probenecid monoacyl glucuronide, while excretion of the unchanged drug is small (∼4%). The other metabolic products results from oxidative attack of the n-propyl side chain and are the monohydroxylated derivatives at the secondary (7.2%–12.5%), terminal (1.6%–3.7%) positions, and the carboxy (6.3%–9.2%), N-depropyl (4.6%–8.0%) compounds. These metabolites are excreted mostly in the free form, a small amount of the secondary hydroxy and the N-depropylated drugs (3.4%) being present probably as β-acyl glucuronides. Apparently, species differences in the metabolic disposition of probenecid are evident, since previous rat biliary excretion studies had reported the absence of the acyl glucuronide of probenecid and that the other metabolites are found mostly as β-ether glucuronides. The possibility that the oxidized metabolites are formed from a common intermediate is discussed.