Metabolism and disposition of the dipeptidyl peptidase IV inhibitor teneligliptin in humans

Abstract

1. The absorption, metabolism and excretion of teneligliptin were investigated in healthy male subjects after a single oral dose of 20 mg [¹⁴C]teneligliptin.

2. Total plasma radioactivity reached the peak concentration at 1.33 h after administration and thereafter disappeared in a biphasic manner. By 216 h after administration, ≥90% of the administered radioactivity was excreted, and the cumulative excretion in the urine and faeces was 45.4% and 46.5%, respectively.

3. The most abundant metabolite in plasma was a thiazolidine-1-oxide derivative (designated as M1), which accounted for 14.7% of the plasma AUC (area under the plasma concentration versus time curve) of the total radioactivity. The major components excreted in urine were teneligliptin and M1, accounting for 14.8% and 17.7% of the dose, respectively, by 120 h, whereas in faeces, teneligliptin was the major component (26.1% of the dose), followed by M1 (4.0%).

4. CYP3A4 and FMO3 are the major enzymes responsible for the metabolism of teneligliptin in humans.

5. This study indicates the involvement of renal excretion and multiple metabolic pathways in the elimination of teneligliptin from the human body. Teneligliptin is unlikely to cause conspicuous drug interactions or changes in its pharmacokinetics patients with renal or hepatic impairment, due to a balance in the elimination pathways.

• DPP-4 inhibitor
• excretion
• human
• mass balance
• metabolism
• teneligliptin

Acknowledgements

We thank Fumihiko Akahoshi (Medicinal Chemistry Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Saitama, Japan) for the synthesis and supply of [¹⁴C]teneligliptin and the metabolite standards. We acknowledge Yasuo Takamatsu, General Manager of DMPK Research Laboratories, for encouragement and great interest in this study.