Evaluation of age-related changes in teneligliptin pharmacokinetics in Japanese and Caucasian subjects using a physiologically based pharmacokinetic model

Abstract Teneligliptin, an antidiabetic dipeptidyl peptidase-4 inhibitor, is widely used in older patients. However, the pharmacokinetic data for teneligliptin in older people are limited. Therefore, we simulated the plasma concentration–time profiles for teneligliptin at a dose of 20 mg (single and multiple doses) in virtual Japanese (20–70 years old) and Caucasian (20–98 years old) subjects using the physiologically based pharmacokinetic (PBPK) simulator Simcyp. In both populations up to 70 years old, the area under the plasma concentration–time curve (AUC) of teneligliptin tended to increase slightly with age. However, no clear age-related change in the maximum plasma concentration (C max ) of teneligliptin was observed. In Caucasians ≥70 years old, the AUC tended to increase but the ratio of change in C max was smaller than that in AUC. In both populations, there were positive correlations between AUC and age, but not between C max and age. The results of PK simulations using the PBPK model across a wide age range, which included older subjects for whom clinical PK data are difficult to collect, suggested that there are some age-related changes in AUC of teneligliptin, and that C max is less affected by age than AUC.