Effect of diet and gavage on the dose- and dose-mode-dependent absorption and metabolism of bidisomide in rat

I. The metabolism of bidisomide was investigated to examine how dose and mo de of drug administration (i.e. diet admixture versus oral solution) affect the absorption and metabolism of bidisomide in the toxicity studies. 2. After dietary admixture, bidisomide was more absorbed and less metaboliz ed at the higher doses. Reduced metabolism at the high doses resulted from saturation of stereospecific formation of the N-desisopropyl-arylhydroxy bi disomide (NDABD) metabolite. 3. The rat-specific NDABD metabolite was formed only from (-)-bidisomide on incubation with rat liver microsomes. 4. After oral solution dosing, absorption was increased and metabolism redu ced compared with the dietary admixture. 5. After 24-h infusion, plasma concentrations of radioactivity were approxi mately dose-proportional. However, the concentrations in the liver were sim ilar at the 200 and 400 mg/kg doses due to saturation of liver uptake of th e NDABD metabolite.