Search

The absorption, distribution, and excretion of radioactivity were investigated following a single oral administration of 14C-pramipexole to rats at a dose of 0.5 mg/kg. The protein binding of the drug was also investigated in vitro and in vivo. 1. The total radioactivity in plasma reached the maximum at about 1.5 hr after oral administration of 14C-pramipexole to male and female rats. The half-lives of radioactivity in plasma were about 48 and 41 hr in male and female rats, respectively, as determined from the data at 24 to 72 hr after administration. The Cmax was decreased in the presence of food, but total absorption of radioactivity remained unaffected. 14CPramipexole was well absorbed throughout the duodenum, jejunum and ileum, but not in the stomach. 2. The radioactivity in most tissues after oral administration of 14C-pramipexole to male rats reached Cmax at 2 hr, being higher in liver, kidney, hypophysis and salivary gland. The radioactivity in the whole brain was higher than that in plasma at 2 and 6 hr after administration. At 48 hr after oral administration, the radioactivity in most tissues except blood had decreased to below 1/10 of the respective maximum concentration. The ratio of the concentration in blood cells to that in plasma was in the range of 1.63-7.15 at 0.5 to 48 hr after oral administration. 3. The binding of 14C-pramipexole at concentrations of 10-1000 ng/ml to rat plasma protein in vitro was about 15-18% and that at concentrations of 0.5-50 ng/ml to human serum protein in vitro was about 17-26%. The percentage of radioactivity bound to rat plasma protein within 2 hr after oral administration of 14Cpramipexole to male rats was below 20%. After 2 hr, the ratio of plasma protein binding increased with time, and then the percentage of radioactivity bound to rat plasma protein was about 67% at 48 hr. 4. The amount of radioactivity excreted in urine and feces within 168 hr after oral administration of 14C-pramipexole to male rats were 59.0% and 44.0% of the dose, respectively. Within 48 hr after intraduodenal injection of the bile obtained from other rats which had been administered 14C-pramipexole (0.1 mg/kg) intravenously, about 4% of the injected radioactivity was excreted in the bile. 5. The radioactivity in milk after oral administration to lactating rats was 2-5 times higher than that in plasma at all times from 0.5 to 48 hr, but the half-life of radioactivity in milk was shorter than that in plasma.

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.