Polymorphic acetylation of hydralazine.

The acetylation of hydralazine has been studied in hypertensive patients undergoing maintenance therapy with the drug. The patients were acetylator phenotyped with sulfamethazine. Using gas-liquid chromatography and high-pressure liquid chromatography, hydralazine and two of its acetylated metabolites, methyltriazolophthalazine (MTP) and 3-hydroxymethyltriazolophthalazine (HOMTP), have been determined in the 0- to 24-hr urine. The excretion of hydralazine and HOMTP but not MTP was found to be related to the acetylator phenotype. The metabolic ratio HOMTP: hydralazine showed a bimodal distribution and the average ratio for slow acetylators (1.6) was lower than the ratio in rapid acetylators (14.9). It is concluded that hydralazine is polymorphically acetylated in man. The acetylated metabolite HOMTP was not, however, the major metabolite reported previously.