COMPARATIVE STUDIES ON THE FATE OF ^<14>C-DIPYRIDAMOLE (RA8) AFTER SINGLE AND MULTIPLE ADMINISTRATION IN RATS

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1) Absorption, distribution and excretion of ^<14>C-Dipyridamole (RA 8) were studied comparatively after the administration of single intravenous (5 mg/kg), single oral (10 mg/kg) and multiple oral (10 mg/kg, once a day for one week) dosages in rats. 2) The blood level of radioactivity after oral administration showed a monophasic slow elimination with a half-life (t_<1/2>) of about 10 hrs. The apparent absorption rate was not so high (t_<1/2> : 0.72 hr), therefore, it took about 3 hrs to reach the maximum level. 3) When the drug was applied intravenously, radioactivity in blood decreased tri-phasically, but the terminal phase, which appeared 12 hrs after the application, showed the same elimination rate as that of p.o. application, i.e. t_<1/2> : about 10 hrs. 4) The observed values of radioactivity during and after the multiple dosing regimen fitted well on the simulation curve derived from the results of a single administration. 5) Radioactivity was mainly distributed in the alimentary canal, liver and kidney, which were isolated after single or multiple oral administration. No radioactivity was found in CNS. Whole body autoradiogram obtained after intravenous or oral administration also supported the results of distribution as above. 6) No considerable accumulation of radioactivity was recognized in any tissues after the multiple dose in the rat.
日本トキシコロジー学会の論文
1980-11-15