Metabolic Fate of a New Dihydropyridine Calcium Antagonist, AE0047 (II): Lymphatic Absorption and Distribution of AE0047 in Rats

The tissue distribution of 14C-AE0047 in rats was studied after single or consecutive oral administrations by the whole body autoradioluminography and by the excised tissue-liquid scintillation method. The transfer of 14C-AE0047 to lymphatic system during the absorption was also investigated. 1. The maximum levels in the lymph, liver and adrenals, which showed higher levels of radioactivity than other tissues, except gastro-intestinal tract, were found at 3 hr, and the levels of radioactivity in muscle, fat, brown fat, skin, bone marrow, testis and eyeball reached the maximum at 6 hr after an oral administration of 14C-AE0047. The level of radioactivity in central nervous system was the lowest. The radioactivity in plasma decreased with a half-life of about 1.2 day, and those in each tissue did with half-lives of 2 to 4 days. 2. The tissue distribution pattern obtained after consecutive doses of 14C-AE0047 for 14 days was similar to that after a single dose. Almost all tissues, except the adipose tissue, bone marrow and mesenteric artery, showed 3 to 6 times higher radioactivity levels than after a single dose, which were almost the same values as the predicted accumulation factor. No particular accumulation of radioactivity in main tissues was observed after the consecutive oral administration of 14C-AE0047. 3. The radioactivity, 5.3% of the dose, transferred to lymph recovered from the thoracic duct within 48 hr after an oral dosing to rats.