THE COMPARATIVE PHARMACOLOGY IN MAN AND THE RAT OF THE RIBOFLAVIN ANALOGUE, 6,7-DIMETHYL-9-(2'-ACETOXYETHYL)-ISOALLOXAZINE, U-2112

¹ National Cancer Institute, National Institutes of Health, Bethesda, Maryland

6,7-Dimethyl-9-(2'-acetoxyethyl)-isoalloxazine, or U-2112, a riboflavin analogue capable of inducing riboflavin deficiency, growth inhibition and regression of established tumors in rats was subjected to clinical and pharmacological trial in man.

In ten patients with advanced neoplastic diseases U-2112 did not produce evident riboflavin deficiency or tumor regression.

Studies of plasma flavin concentrations and urine flavin excretion did not yield significant quantitative differences between man and the rat.

The metabolism of U-2112 was found to be different in these species. A significant percentage of the administered drug was excreted in the urine unaltered by the rat, whereas hydrolysis of the drug was practically complete in man.

This species difference in metabolism of U-2112 may account for the ability of the drug to produce riboflavin deficiency in the rat and for its apparent inactivity in man, since the unaltered drug, U-2112, is ten times more active as a riboflavin antagonist for L. casei than is U-2113, the only other active urinary metabolite.