INHIBITORY EFFECT OF DRUGS WITH A KETONE GROUP ON REDUCTION OF ACETOHEXAMIDE CATALYZED BY CARBONYL REDUCTASE FROM RABBIT KIDNEY

The reduction of acetohexamide catalyzed by carbonyl reductase from ra bbit kidney was inhibited by befunolol, moperone, levobunolol, daunoru bicin and loxoprofen, which have a ketone group within their chemical structures and are substrates for the enzyme. A significant correlatio n was observed between the common logarithm of V-max/K-m values of the enzyme for befunolol, moperone, levobunolol and daunorubicin and the percentage inhibition of the enzyme, confirming that these drugs are c ompetitive substrates of the enzyme with respect to acetohexamide. How ever, the plot for loxoprofen, a nonsteroidal anti-inflammatory drug w ith a ketone group, was apparently distant from the regression line ob tained. Although nonsteroidal anti-inflammatory drugs with a ketone gr oup such as suprofen and fenbufen were not reduced by the enzyme, they strongly inhibited the reduction of acetohexamide catalyzed by the en zyme.