EFFECT OF BOF-4272 ON THE OXIDATION OF ALLOPURINOL AND PYRAZINAMIDE IN-VIVO - IS XANTHINE DEHYDROGENASE OR ALDEHYDE OXIDASE MORE IMPORTANT IN OXIDIZING BOTH ALLOPURINOL AND PYRAZINAMIDE

Allopurinol or pyrazinamide was administered to rats treated with BOF- 4272 (a potent xanthine oxidase inhibitor) to investigate to what degr ee xanthine dehydrogenase participates in the oxidation of these agent s. BOF-4272 markedly decreased the plasma concentration and the urinar y excretion of both oxypurinol and 5-hydroxypyrazinamide. It also decr eased the sum of the urinary excretion of allopurinol and oxypurinol a nd that of pyrazinamide and its metabolites, although it did not affec t the sum of the plasma concentrations of allopurinol and oxypurinol a t 105 min after administration of allopurinol or the plasma concentrat ion of pyrazinamide during the period after the administration of pyra zinamide. These results suggested that BOF-4272 almost completely inhi bited the oxidation of allopurinol and pyrazinamide and had some effec t on the excretion and/or the tissue incorporation of these two compou nds. Since the in vitro study demonstrated that BOF-4272 did not inhib it the activity of aldehyde oxidase which oxidized both allopurinol to oxypurinol and pyrazinamide to 5-hydroxypyrazinamide, the results sug gested that xanthine dehydrogenase was the more important enzyme in co nverting allopurinol to oxypurinol and pyrazinamide to 5-hydroxypyrazi namide.