Clofibrate and clofibric acid: comparison of the metabolic disposition in rats and dogs.

In rats, equimolar oral doses of [14C]clofibrate and [14c]clofibric acid produced essentially the same profiles of blood levels, tissue distribution and excretion of radioactivity. Both compounds were completely absorbed, and all radioactivity found in the serum was due to clofibric acid (CPIB). Tissues contained readily detectable radioactivity levels, but the concentration was generally lower than in serum. A large proportion of CPIB in liver, heart, kidney, fat and muscle was associated with intracellular space. In rat urine, CPIB was present both free and conjugated with glucuronic acid. Approximately 97% of the serum CPIB was not conjugated. Identical decreases in serum lipids and hepatic cholesterol synthesis were observed in rats treated for 1 week with either compound. In dogs, the serum contained 40% more radioactivity after [14C]clofibric acid than after an equimolar oral dose of [14C]clofibrate; approximately 88% of the serum radioactivity was due to CPIB. Some biliary excretion was detected. The extent of binding to serum protein varied with concentration of CPIB and with the species; the affinity was in the order man greater than dog greater than rat. The results demonstrate that clofibric acid and clofibrate are metabolically and pharmacologically equivalent in rats, but not in dogs. The data are in accordance with the view that the pharmacological activity of clofibrate is due to clofibric acid.