Effect of sulphonylureas (tolazamide, tolbutamide and chlorpropamide) on the metabolism of diphenylhydantoin in the rat

The blood sugar lowering sulphonylureas chlorpropamide, tolazamide and tolbutamide showed competitive inhibition of diphenylhydantoin hydroxylation by the 9000 g-supernatant of rat liver homogenates. Tolbutamide was the strongest inhibitor and chlorpropamide the weakest. The enzyme kinetics could not be presented satisfactory by Lineweaver-Burk plots; therefore log-dose response curves were used and the potency of the inhibitors was calculated according to the method of Arunlakshana and Schild. The relative inhibitory potency of the three sulphonylureas chlorpropamide-tolazamide-tolbutamide was 1:2·5:4·3.