The effect of dose on acetylator phenotype distribution of hydralazine has been determined, The acetylated metabolites methyltriazolophthalazine (MTP) and 3-hydroxymethyltriazolophthalazine (3-OHMTP) and acid-labile hydralazine (HP) were determined in the 0- to 24-hr urine of patients receiving various doses. The difference between the mean value for the ration 3-OHMTP:HP in the rapid and slow acetylators varied with dose, the greatest difference being after a 200 mg (100 mg twice daily) dose. The distribution of the ratio became less clearly bimodal at lower doses, with overlap between phenotypes occurring at doses of 100 mg (50 mg twice daily) or less. The most effective dose for discriminating between acetylator phenotypes was found to be 200 mg (100 mg twice daily).

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.

thereby permitting the fairly confident exclusion of hypertension as such as the precipitating factor.It was considered possible that phenobarbitone present in the serum might interfere with the laboratory procedure and result in artificially low oestriol values, but this was discounted after evidence showed that the behaviour of the assay was not appreciably affected by the in-vitro addition of phenobarbitone in amounts considerably above those reached during normal treatment.