Intestinal absorption and excretion of troglitazone sulphate, a major biliary metabolite of troglitazone

1. Deconjugation by sulphate transfer and intestinal absorption of troglita zone sulphate (M1), the major metabolite of a thiazolidinedione antidiabeti c drug, troglitazone, were studied in the male F344 rat using C-14-troglita zone, C-14-M1 and S-35-M1. 2. Some part of M1, produced in the liver and excreted mostly in the bile, was deconjugated in the intestine to the parent compound, troglitazone, by arylsulphate sulphotransferase originated from intestinal flora. However, d econjugation of M1 was not catalyzed by arylsulphatases. Caecal injection o f M1 led to the appearance of troglitazone and M1 in plasma. 3. Biliary excretion mostly as M1, and, following absorption, as M1 and tro glitazone after deconjugation, were indicated as the basis for the enterohe patic circulation of troglitazone. 4. Enterohepatic circulation may prolong the pharmacological effects of tro glitazone.