Studies on the Metabolic Fate of Pramipexole (SND 919 CL2Y). (II). Absorption and Distribution after Repeated Oral Administration to Rats.

Abstract

The absorption and distribution of radioactivity were investigated following a 14-day period of daily oral administration of 14C-pramipexole (0.5 mg/kg/day) to male rats. 1. When measured 24 hr after each of 14 repeated daily administrations of 14C-pramipexole to male rats, the level of radioactivity in plasma rose as the number of doses increased, and reached a steady state after 12 or 13 doses. The elimination of radioactivity from the plasma after the last dose was similar to that after a single administration. 2. At 1 hr after the 14th administration, the level of radioactivity reached the maximum in most tissues. High levels were observed in the liver and kidney, being about 22 and 14 times higher than that in the plasma, respectively. At 168 hr after the last dose, the levels of radioactivity in the liver and kidney were very much higher than that in plasma. The elimination of radioactivity from most tissues after the last dose was parallel to that from plasma, except the spleen and kidney, where an accumulation was observed. 3. After the last administration, the ratio of the concentration in blood cells to that in plasma gradually increased with the lapse of time. The elimination of radioactivity from blood cells was very much slower than that from plasma. The relative increase of radioactivity in blood cells at the late stage after drug administration may be attributed to metabolites of pramipexole.