Kinetics of hydralazine elimination

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Abstract
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.

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