Kinetics of hydralazine elimination.
Hydralazine was given orally in single doses of 10, 25, and 50 mg to 2 slow-acetylating subjects, while 2 rapid-acetylating subjects also received 100- and 150-mg doses on different occasions. Administration of the 50-mg dose to the subjects who were slow acetylators and the 150-mg dose to those who were rapid acetylators caused a disproportionately large increase in the amount of unchanged drug appearing in the systemic circulation as judged from the increases in the ratios of areas under concentration-time curves (AUC) to dose. A modification of the gas-liquid chromatographic hydralazine assay allowed the simultaneous determination of hydralazine and its acetylated metabolite, 3-methyl-s-triazolo-3,4,a-phthalazine (MTP), in serum. It was found that the disproportionately large increases in the AUC/dose ratio of hydralazine upon intake of 50 or 150-mg doses by the slow and rapid-acetylating subjects, respectively, were paralleled by a decrease in the ratio AUCMTP/AUChydralazine during a 6-hr observation period. It is concluded that the acetylation of hydralazine in man is a capacity-limited process.
D000107:Acetylation; D000284:Administration, Oral; D001682:Biological Availability; D002849:Chromatography, Gas; D005260:Female; D006207:Half-Life; D006801:Humans; D006830:Hydralazine / Q000097:blood / Q000378:metabolism*; D008297:Male; D008722:Methods; D010793:Phthalazines / Q000097:blood
D010793:Phthalazines; D006830:Hydralazine