RT Journal Article
SR Electronic
T1 The in vitro metabolism of hydralazine.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 255
OP 259
VO 13
IS 2
A1 A J Streeter
A1 J A Timbrell
YR 1985
UL http://dmd.aspetjournals.org/content/13/2/255.abstract
AB Hydralazine was metabolized in vitro to phthalazine and phthalazine-1-one by microsomal enzymes requiring NADPH. Hydrazine was not detected as a metabolite under these in vitro conditions. Addition of 1-hydrazinophthalazin-4-one, a possible intermediate metabolite, decreased covalent binding to protein but also decreased metabolism. Phthalazine and phthalazin-1-one also decreased covalent binding to protein to a lesser extent. N-Acetylcysteine significantly decreased the level of phthalazine and phthalazin-1-one detected in microsomal incubations. The results are consistent with a reactive intermediate, but not 1-hydrazinophthalazin-4-one, being responsible for both covalent binding and production of phthalazine.