Metabolism in rats of 3-phenoxybenzyl alcohol and 3-phenoxybenzoic acid glucoside conjugates formed in plants

Upon single oral administration to rats, the mono-, di- and tri-glucose conjugates of ¹⁴C]-3-phenoxybenzyl alcohol ( I ) or the mono-glucose conjugate of ¹⁴C]-3-phenoxybenzoic acid ( II ) were rapidly hydrolysed and extensively eliminated in the urine mostly as the sulphate conjugate of 3-(4-hydroxyphenoxy)benzoic acid ( X ). The faecal elimination was a minor route, whereas the biliary excretion was about 42% of the dose and the glucuronide conjugates of I , II and X were common major metabolites. The biliary glucuronides were cleaved in the small intestine to the respective aglycones, which were reabsorbed, metabolised further, and excreted in the urine as the sulphate conjugate of X . Although small amounts of the mono-, di-and tri-glucosides were found in the 0.5-h blood and liver samples following oral administration of the tri-glucoside of I , they were not detected in the urine, bile or faeces. Similarly the sulphate conjugate was one of the major urinary metabolites of germ-free rats, dosed with the ¹⁴C-glucosides via the oral or the intraperitoneal route, although they were excreted unchanged in certain amounts in the urine and faeces. The glucose conjugates were cleaved in vitro by gut microflora and in various rat tissues, including blood, liver, small intestine and small intestinal mucosa. The tissue enzymes showed a different substrate specificity in hydrolysis of the glucosides. However, they were not cleaved in gastric juice, bile, pancreatic juice or urine.