Abstract
INTRODUCTION: Drugs often show differing pharmacokinetic (PK) profiles, such as higher plasma concentrations, in older people than in younger people owing to age-related decreases in physiological functions. However, it is difficult to evaluate the PK in older populations. Therefore, we simulated the plasma age-related changes in the PK of teneligliptin, a dipeptidyl peptidase-4 inhibitor, using physiologically based PK (PBPK) models. METHODS: The previously developed PBPK model was revalidated by comparison between simulated data and clinical study data that included older subjects (up to 75 years old). We then 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 European descent (20-98 years old) subjects. PK parameters were calculated by race and age group. RESULTS: We confirmed the validity of the previous PBPK model by comparison between simulated data and clinical study data. In the evaluation of age-related changes in PK after single and multiple doses using the PBPK model, the area under the plasma concentration-time curve (AUC) of teneligliptin tended to increase slightly with age in both populations up to 70 years old. However, no clear age-related change in the maximum plasma concentration (C(max)) of teneligliptin was observed. In the European descent subjects aged ≥ 70 years, the AUC tended to increase but the ratio of the 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. CONCLUSION: The simulation using a PBPK model showed a tendency for the AUC of teneligliptin to increase with age, whereas C(max) was less affected by age than AUC.