1999 Volume 14 Issue 6 Pages 432-436
Plasma concentration and distribution of 14C-telmisartan after repeated oral administration at a dose of 1 mg/kg given once a day for 7 days to fed male rats were investigated.
1. The pharmacokinetic parameters of 14C-telmisartan in plasma were as follows. The Cmax t1/2(12-48hr), AUC(0-48hr) and MRT(0-48hr) values of 14C-telmisartan in plasma after the final administration was 61.95 ng eq./ml, 12.76 hr, 1529.33 ng eq.·hr/ml and 14.85 hr, respectively. Plasma levels of radioactivity peaked at about 7 hr after the final administration. The levels of radioactivity in plasma before each administration (trough value) for 7 days did not increase with increasing number of administrations. The radioactivity profile in plasma after the first and final administrations was very similar.
2. Radioactivity levels in tissues after 7-day repeated oral administration decreased with time. The levels of radioactivity in all tissues were lower than the plasma levels at all sampling points, except in the gastrointestinal tract, including its content, liver, kidney and lung. Radioactivity in the liver was eliminated in parallel with that in plasma, and the other tissue levels had become undetectable at 72 hr or 168 hr. The distribution pattern of radioactivity was very similar to that after a single administration to fasted male rats.
3. From 4 hr to 72 hr after administration, the ratio of the concentration in blood cells to that in plasma was in the range of 0.1-0.3. There was little distribution of radioactivity to blood cells, in agreement with the finding after a single oral administration.
