1. Four healthy male volunteers (2 fast acetylators, 2 slow acetylators) received a single oral dose of hydralazine hydrochloride. The fast acetylators each received a dose of 1 mg/kg of bodyweight, whereas the slow acetylators each received a dose of 0.5 mg/kg of bodyweight. Plasma concentrations of 'apparent' hydralazine and of pyruvic acid hydrazone (HPH), the major plasma metabolite of hydralazine, were followed for 6 h post-dose. A comparison with 'true' hydralazine levels was made for the fast acetylator subjects. The plasma decay of the concentrations of the substances measured was of first order. During the absorption and distribution phase, until peak levels were reached 'apparent' hydralazine concentrations in all 4 volunteers consistently exceeded the simultaneously measured concentrations for HPH. Since this excess could not be attributed to hydralazine, other acid labile compounds, like other hydrazones of hydralazine with endogenous keto-bodies could account for it. It is concluded that no correlation exists for the measurement of 'apparent' hydralazine and HPH, as has been claimed in the literature. 2. 14C-Labelled hydralazine hydrochloride was administered i.v. to a rabit in a dose of 10 μmol/kg of bodyweight. Time course in plasma was determined for total 14C, 'apparent' hydralazine and HPH. The rapid formation of HPH in vivo was demonstrated. The administered radioactivity was recovered almost quantitatively in urine. 3. 14C-Labelled HPH was administered i.v. to two rabbits and the level of total 14C, 'apparent' hydralazine and HPH monitored in plasma and urine. Good agreement of the analytical techniques was observed for the first 30 min postdose in plasma, testifying to the fact that little or no metabolism of HPH occurred. This is further corroborated by the fact that the radioactivity was excreted nearly quantitatively in urine, mostly as unchanged parent drug.
|Original language||English (US)|
|Number of pages||6|
|State||Published - May 8 1981|
ASJC Scopus subject areas
- Drug Discovery