Individual Variability of Carbonyl Reductase Activity for Acetohexaminde in Human Erythorcytes

Acetohexamide, an oral antidiabetic agent, is metabolized by carbonyl reductase to hydroxyhexamide, which has a higher hypoglycemic potency than the parent compound. In the present study, interindividual variability of carbonyl reductase activity in erythrocyte was examined. Enzyme activity in 31 healthy subjects (23.9 plus minus 3.4 years, mean plus minus SD) was monitored by measuring formation of hydroxyhexamide using HPLC methods. Using 0.5 mM acetohexamide as substrate, reductase activity of 6.06 plus minus 0.06 nmol min(minus sign1) gHb(minus sign1) (range: 5.9--6.2) with a coefficient of variation of 15% was observed in erythrocytes. Acetohexamide-reducing activity in erythrocytes showed a normal distribution and the interindividual variability of the reductase activity was found to be small, implying that the large variability reported for the acetohexamide plasma half-life is not caused by the amount of reductase enzyme in erythrocytes.