Stimulation of drug metabolism by ascorbic acid in weanling guinea-pigs

Drug metabolism activities such as O-demethylase and N-demethylase and liver microsomal electron transport components including cytochrome P-450 and NADPH-cytochrome P-450 reductase were determined in weanling guinea-pigs under vitamin C deficiency as well as with normal and high intake of the vitamin. Animals depleted of the vitamin for only 8 days, with no signs of scurvy or weight loss, had decreased drug enzyme activities. Further depletion of the vitamin resulted in marked reduction of the microsomal drug-metabolizing system. Furthermore, administration of high amounts of ascorbic acid (2–200 mg/day) led to significant increases in liver drug oxidation activities and electron transport components. Studies of K_m values in microsomes from vitamin C-deficient, normal and animals given high supplements of vitamin C showed no difference in the apparent affinity or V_max of a typical drug oxidation reaction, N-demethylation. Specificity studies indicate that ascorbyl palmitate or d-isoascorbic acid can replace the vitamin, in part, in maintaining drug metabolism.