METABOLISM OF PROCAINAMIDE TO A HYDROXYLAMINE BY RAT AND HUMAN HEPATIC MICROSOMES

Abstract

Procainamide was previously oxidized to a reactive metabolite. This reactive metabolite was speculated to be a hydroxylamine and might be responsible for the syndrome of procainamide-induced lupus. Procainamide is metabolized to a hydroxylamine by rat and human hepatic microsomes. The extent of this metabolic oxidation was quantitated by HPLC [high-performance liquid chormatography] after conversion of the hydroxylamine to the more stable nitro derivative of procainamide. Formation of the hydroxylamine required NADPH, active microsomes and O2 and was inhibited by CO, SKF 525-A [proadifen hydrochloride] and cimetidine. Formation of the hydroxylamine was also studied as a function of time, microsomal protein concentration and procainamide concentration.