Rat-plasma metabolites of ciglitazone, a new antidiabetic agent

Abstract

1. The rat-plasma metabolites of ciglitazone, a new antidiabetic agent, were characterized by g.I.e.-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′-hydroxy-cyclohexyl 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.

2. All monohydroxy and monoketo metabolites showed hypoglycaemic and hypotrigly-ceridemic activities in genetically obese-diabetic mice.

3. These results suggest that the pharmacological activities of ciglitazone are due, at least partly, to the metabolites.