Quantitative analysis of cresol and its metabolites in biological materials and distribution in rats after oral administration.

We investigated kinetics of p-cresol, m-cresol, and their glucuronide and sulfate metabolites in blood and organs of rats. We established a quantitative analysis method for the measurement of the concentrations of cresols. Endogenous beta-glucuronidase, an enzyme which hydrolyses the glucuronide, existed in rat organs, and it influenced the procedures for cresol hydrolysis of sulfatase. It was necessary for the quantitative analysis of cresol sulfate in organs to add the saccharolactone (d-saccharic acid 1,4-lactone) as an inhibitor for beta-glucuronidase. On the other hand, endogenous sulfatase did not interfere in the quantitative analysis of the glucuronide. It was found that cresol administered via the stomach tube diffuses directly through gastric and small intestinal walls because the unconjugate cresol concentrations were extremely high not only in the liver, but also in the spleen. The unconjugates of cresol in the liver, spleen and kidney were detected in high concentrations even when the unconjugates were not detected in the blood. m-Cresol was easily metabolized to sulfate, and the p-cresol to glucuronide in rats. The concentration ratios of m-cresol to p-cresol in blood and organs were different from the rate of the cresol soap solution that was administered. The pharmacokinetics was different between p-cresol and m-cresol in rats.