Metabolism of hydralazine in man. Part II: Investigation of features relevant to drug safety.

The metabolism of hydralazine (1-hydrazinophthalazine hydrochloride, Apresoline) was investigated in 17 hypertensive patients of known acetylator status who were chronically treated with oral doses of 50 mg b.i.d. or 100 mg b.i.d. hydralazine. The acetylator status was assessed either by the monoacetyldapsone/dapsone ratio or by the isoniazide plasma half-life. In each patient the tests were performed on two different days of treatment and they included the analyses of four hydralazine metabolites (NAc-HPZ, 3OH-MTP, MTP and TP), as well as apparent hydrazine in urine and also the determination of plasma concentrations of apparent hydralazine. All data of the two experiments performed within an interval of at least five days were in good agreement, thus indicating that the patients were in pharmacokinetic steady states. No correlation was detectable between any of the determined amounts of metabolites of hydralazine and the assigned acetylator status of the patients. On the other hand the rank order of the urinary yields of the two main metabolites NAc-HPZ and 3OH-MTP suggest to be a representative scale for the patients' status in respect to the biotransformation of the drug itself. The urinary yield of apparent hydrazine is dependent on the pH applied during the analyses and is not correlated with any of the other data recorded. The findings of the present study support the assumption that measuring a relevant prominent metabolite of the drug itself may lead to a more reliable assessment of the particular metabolic status of the patients than by classification through a non treatment related foreign compound.(ABSTRACT TRUNCATED AT 250 WORDS)