The tissue distribution of teneligliptin, a dipeptidyl peptidase (DPP)‐4 inhibitor, was investigated in rats, and compared with tissue distributions previously reported for other DPP‐4 inhibitors. Following the oral administration of [14C]teneligliptin to Sprague–Dawley rats, it was predominantly distributed to the kidney and liver, followed by the lung, spleen and pituitary gland. The elimination half‐life (t1/2) of [14C]teneligliptin was 68.3 and 69.0 h in the kidney and liver, respectively; these values were about 10 times greater than the plasma t1/2. Of note, the elimination of [14C]teneligliptin from tissues with high DPP‐4 activity (kidney, liver and lung) was slower in wild‐type rats than in DPP‐4‐deficient rats, especially in the kidney. By contrast, in the heart and pancreas, which weakly express DPP‐4, no difference was observed in [14C]teneligliptin concentrations between the two animal strains. In the kidney, most radioactivity was attributable to unchanged teneligliptin from 0.5 to 72 h after administration. The marked difference in the distribution of [14C]teneligliptin between the two strains suggests that the high binding affinity of teneligliptin for DPP‐4 is involved in its tissue distribution. The currently marketed DPP‐4 inhibitors are highly distributed to the liver, kidney and lung, but the extent of tissue distribution varies greatly among the drugs. The differences in the tissue distributions of DPP‐4 inhibitors might be related to differences in their pleiotropic effects.
Keywords
DPP-4 inhibitor; tissue distribution; teneligliptin