Metabolism of the antiarrhythmic agent, indecainide, in rats, dogs, and monkeys

The biotransformation of indecainide, a potent new antiarrhythmic agent, has been studied in rats and dogs. Indecainide was excreted in the urine primarily as the unchanged compound. The major urinary metabolite was desisopropyl indecainide which accounted for approximately 5% of the urinary radioactivity in both species. This metabolite was also detected in the plasma of rats, dogs, and monkeys. Peak plasma levels of the amine metabolite were 15 and 19% of the peak plasma levels of indecainide in rats and dogs, respectively. Loss of isopropylamine resulted in the formation of an aldehyde intermediate which was stabilized as the cyclic acylaminocarbinol. An acidic metabolite presumably derived from oxidation of the aldehyde was detected as well as a cyclic imide metabolite. An additional minor metabolite corresponding to N-formyl indecainide was observed in the urine but the mechanism of its formation is unknown.