67536-13-4Relevant articles and documents
In vitro kinetic studies of the reaction of hydralazine and its acetone hydrazone with pyruvic acid
Iwaki,Ogiso,Ito
, p. 280 - 283 (1988)
To understand the reaction between hydralazine (HP) or its acetone hydrazone (HAH), a metabolite of HP and pyruvic acid, a new selective HPLC method for simultaneous determination of HP, HAH, and hydralazine pyruvic acid hydrazone (HPH) was developed. In vitro degradation of HAH and formation HP and HPH were investigated at pH 7.4 and 37°C in the presence or absence of pyruvic acid. Hydralazine degraded slowly according to an apparent first-order rate (7.46 x 10-2 h-1). The degenerative reaction of HAH, accompanied by simultaneous hydrolysis to the parent drug HP, was also subject to apparent first-order loss (3.00 x 10-1 h-1). In addition, HAH was partly converted to HP and HPH in the presence of pyruvic acid. For the formation pathway of HPH, a model that included the direct reaction of HAH with pyruvic acid and the secondary formation mediated by back-conversion to HP gave a better fit to the experimental data than the model consisting of the latter reaction only. About 10% of the HPH formed was generated by the direct reaction of HAH with pyruvic acid, based on the rate constants estimated. These results suggest that the formation of HPH is not all accomplished through back-conversion to HP.
Determination of hydralazine pyruvic acid hydrazone and its correlation with 'apparent' hydralazine
Haegele,Talseth,Skrdlant,Shepherd,Huff
, p. 357 - 362 (2007/10/02)
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.
