Effect of glimepiride on the pharmacokinetics of teneligliptin in healthy Korean subjects

What is known and objective: Teneligliptin is a DPP-4 inhibitor used for the treatment of type 2 diabetes mellitus, commonly prescribed in combination with glimepiride. Teneligliptin is metabolized by CYP3A4, and glimepiride might be partly metabolized by CYP3A4. The aim of the study was to investigate the possible effect of glimepiride on the pharmacokinetics of teneligliptin in healthy subjects. Methods: A repeated dose, open-label, fixed-sequence study was conducted in 26 healthy subjects. All participants were administered 20 mg teneligliptin daily for 6 days. On day 7, 4 mg glimepiride was administered together with 20 mg teneligliptin. Plasma teneligliptin concentrations were measured at a steady state, and its pharmacokinetic characteristics were compared without and with glimepiride. Results and discussion: No statistically significant difference was found in the effect of glimepiride on teneligliptin pharmacokinetics. The steady-state C_max,ssvalues of teneligliptin without and with glimepiride were 207.01 ng/mL and 202.15 ng/mL, respectively. Its AUC_τ values at steady-state without and with glimepiride were 1527.8 ng · h/mL and 1578.6 ng · h/mL, respectively. The point estimation of geometric mean ratios (GMR) and the 90% confidence interval for both C_max,ss and AUC_τ were within the equivalence range of 0.8-1.25. The results of the present study revealed that glimepiride did not cause pharmacokinetic interaction with teneligliptin in humans. What is new and conclusion: Glimepiride did not affect the pharmacokinetic characteristics of teneligliptin in healthy subjects.