Studies in the rabbit on 3-methyltriazolophthalazine, an acetylated metabolite of hydralazine. Evidence for an alternative route of formation.

The formation and disposition of 3-methyltriazolophthalazine (MTP), an acetylated metabolite of hydralazine (H) was studied in rabbits. Following its iv administration MTP was rapidly and almost completely metabolized. The major metabolite in plasma and urine was found to be a hitherto unrecognized glucuronide conjugate, most likely of the carboxylic acid analogue of MTP. The hydralazine-pyruvic acid hydrazone (HPH), which is a major plasma metabolite of H, was recognized as a more potent source for MPT in vivo than was parent H. MTP was also formed in significant amounts in vitro following incubation of HPH in phosphate buffer. We conclude that MTP can arise directly from HPH. Consequently, MTP and the compounds formed during its further biotransformation may not provide any valid measure of the extent to which H is acetylated in vivo.