Stereospecificity of Esterases Hydrolyzing Oxazepam Acetate

Esterases hydrolyzing the racemic acetate ester of the centrally acting drug oxazepam in mice were examined. Radiolabeled ester administered intravenously was hydrolyzed rapidly in the liver, kidneys, and brain. The distribution of the enzyme activity of liver and brain subcellular fractions was measured. Kinetic data and structure investigation of partially hydrolyzed racemic ester pointed to the stereoselectivity of liver and brain esterases. The preferred hydrolysis of the (R)-(−)-isomer in liver homogenates was attributed mainly to microsomal enzymes, while that of the (S)-(+)-isomer in brain was considered to be due to the mitochondrial fraction. This phenomenon was a common property of all species tested.