Rat-plasma metabolites of ciglitazone, a new antidiabetic agent

The rat-plasma metabolites of ciglitazone, a new antidiabetic agent, were characterized by g.l.c.-mass spectrometry as follows: the 2'-, cis-3'-, trans-3'-, cis-4'- and trans-4'-hydroxycyclohexyl derivatives, and 3'- and 4'-oxocyclohexyl derivatives. The 2'-hydroxycyclohexyl derivative contains cis- and/or trans-isomers (unresolved). Three other metabolites, which were postulated to be dihydroxy derivatives of ciglitazone, were also detected in the plasma. All monohydroxy and monoketo metabolites showed hypoglycaemic and hypotriglyceridemic activities in genetically obese-diabetic mice. These results suggest that the pharmacological activities of ciglitazone are due, at least partly, to the metabolites.