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The metabolic fate of a new antiallergic agent, azelastine (4-(p-chlorobenzyl)-2-[N-methylperhydroazepinyl-(4)]-1-(2H)-phthalazinone hydrochloride) in rats and guinea pigs was investigated using its 14C-labelled compound. The blood level of radioactivity reached the maximum at 1-1.5 hr after oral administration, indicating the rapid absorption of the drug from gastrointestinal tract. A high concentration of radioactivity was detected in the lung of both species following either oral or intravenous administration. The major pathway of excretion of radioactivity was by way into feces, in both species. The radioactivity excreted in feces was attributable to that which was excreted in bile and exsorbed into gastrointegtinal tract. When the drug was given to pregnant rats, the concentration of radioactivity in the fetus was significantly lower than those in placenta and uterus, indicating the limited placental transfer of the drug. The successive oral administration of the drug in lower doses exerted no effect on the activity of microsomal drug-metabolizing enzymes of rat liver, while in higher doses, had a slight effect.

japanese journal of pharmacology/japanese journal of pharmacology

STUDIES ON METABOLIC FATE OF A NEW ANTIALLERGIC AGENT, AZELASTINE (4-(p-CHLOROBENZYL)-2-[N-METHYLPERHYDROAZEPINYL-(4)]-1-(2H)-PHTHALAZINONE HYDROCHLORIDE)