Activity of liver microsomal mono-oxygenases on some epoxide-forming tricyclic drugs. I. Kinetics in vitro

Abstract

1. The mono-oxygenase activity that forms epoxides has been studied in rat liver microsomes using as substrates carbamazepine and cyclobenzaprine, tricyclic drugs which form stable epoxides in vivo and in vitro.

2. A simple gas chromatographic method has been used to determine the amount of epoxide formed and the linearity of the enzymic reaction with time and protein concentration has been demonstrated.

3. Pre-treatment with carbamazepine increases the rate of formation of carbamazepine epoxide in rat liver microsomal preparations.

4. The effect of SKF 525-A on the formation of these epoxides has also been studied.