title: Tissue distribution of teneligliptin in rats and comparisons with data reported for other dipeptidyl peptidase-4 inhibitors.
abstract: We investigated the tissue distribution of teneligliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, in rats, and compared it 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, we observed no difference 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. This article is protected by copyright. All rights reserved.
authors.affiliation: Clinical Pharmacology Department, Development Division, Mitsubishi Tanabe Pharma Co, Chuo-ku, Tokyo, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Nakamaru
authors.affiliation: Research Unit C, Research Division, Mitsubishi Tanabe Pharma Co, Toda, Saitama, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Akahoshi
authors.affiliation: Medical Affairs Department, Mitsubishi Tanabe Pharma Co, Chuo-ku, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iijima
authors.affiliation: DMPK Research Laboratories, Research Division, Mitsubishi Tanabe Pharma Co, Kisarazu, Chiba, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Hisanaga
authors.affiliation: DMPK Research Laboratories, Research Division, Mitsubishi Tanabe Pharma Co, Kisarazu, Chiba, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kume