^<14>C標識N₁-Carboethoxy-N₂-hydrazinophthalazine Hydrochloride(Apiracohl[○!R])の研究(第1報)標識化合物の合成と代謝

抄録

Absorption, distribution, and metabolic fate of Apiracohl [○!R](Ia, Ib) were studied in rats comparing with hydralazine (II). ¹⁴C-labelled Apiracohl [○!R] (Ia) was synthesized from hydralazine (II) and ethyl chloroformate prepared from CH₃¹⁴CH₂OH and phosgene. Excretion of metabolites of ¹⁴C-labelled Apiracohl [○!R](Ib) was rapid, about 80% of the radioactivity appearing in the urine in 24 hr. The following metabolites were identified in the urine of rats : Unchanged Apiracohl [○!R](trace), its hydroxyderivatives (19.2%), hydralazine (trace), hydralazine glucuronide (16.2%), N-acetylhydralazine (6.9%), hydroxyhydralazine (5.9%), 3-oxo-triazolophthalazine (1.5%), and 3-oxo-triazolophthalazine glucuronide (11.7%). From these results, three metabolic pathways were considered : (1) Hydroxylation of Apiracohl [○!R], (2) decarboethoxylation of Apiracohl [○!R], followed by acetylation, hydroxylation, and glucuronic acid conjugation, and (3) cyclization of Apiracohl [○!R] followed by glucuronic acid conjugation.