| Abstract: | We have previously demonstrated that procainamide is oxidized to a reactive metabolite. We speculated that this reactive metabolite might be a hydroxylamine and further that it might be responsible for the syndrome of procainamide-induced lupus. We now report that procainamide is metabolized to a hydroxylamine by rat and human hepatic microsomes. The extent of this metabolic oxidation was quantitated by HPLC after conversion of the hydroxylamine to the more stable nitro derivative of procainamide. Formation of the hydroxylamine required NADPH, active microsomes, and oxygen and was inhibited by carbon monoxide, SKF 525-A, and cimetidine. Formation of the hydroxylamine was also studied as a function of time, microsomal protein concentration, and procainamide concentration. |
