Abstract
14C-Troglitazone was administered to male cynomolgus monkeys (monkey) orally or intraduodenally, and the time course of the plasma concentrations of the radioactivity and of the biliary excretions of the metabolites were investigated. The same was investigated for male marmosets after oral administration of 14C-troglitazone.
1. The main metabolite in the plasma after oral administration to monkeys was the sulfoconjugate of troglitazone (M1). The quinone form metabolite (M3) and glucuronide (M2) of troglitazone were also detected in the plasma.
2. The ratio of the biliary excretion of the radioactivity over a 24-hr period after intraduodenal administration to a bile-fistula cynomolgus monkey was 54.4%, which was as high as that observed in rats and dogs. The main metabolites in the bile were M1 and M2, each accounting for about 40% of the biliary radioactivity. An unknown metabolite, U3, was also detected at a ratio of about 6%. U3 was also detected in the bile after administration of M3, and was show to contain the quinone-like structure.
3. The plasma metabolites after oral administration to marmosets were almost the same as those in the plasma of monkeys. U3 was also observed in the plasma of marmosets.
4. U3 was isolated from the bile and urine of monkey and marmoset after administration of 14C-M3 or M3. According to the MS and NMR spectra, the chemical structure of U3 was determined as the glucuronide of the hydroquinone form of troglitazone, and its was conjugated at position 8"a.
