Effects of renal impairment on the pharmacokinetics and pharmacodynamics of a novel dipeptidyl peptidase-4 inhibitor, evogliptin (DA-1229).

Evogliptin is a novel potent and selective dipeptidyl peptidase-IV (DPP-IV) inhibitor. This study aimed to evaluate the pharmacokinetic and pharmacodynamic characteristics of evogliptin in renal impairment (RI) subjects. An open-label, parallel-group clinical study was conducted on mild, moderate, and severe RI subjects and matched normal renal function (NRF) subjects. A single oral 5 mg dose of evogliptin was administered and serial blood and urine samples were obtained to assess the pharmacokinetic and pharmacodynamic characteristics of evogliptin. Baseline urine samples were collected to evaluate endogenous CYP3A metabolic markers. The plasma exposure to evogliptin and degree of DPP-IV activity inhibition increased with decreasing renal function. The mean areas under the concentration–time curves from 0 to 120 hours were increased by 1.2-, 1.8- and 1.98-fold in the mild, moderate and severe RI subjects, respectively, compared with the NRF subjects. The levels of CYP3A metabolic markers were lower in the RI subjects than in the NRF subjects. The increase in the plasma concentration of evogliptin is unlikely to result in changes in its efficacy or safety, considering the results of previous clinical studies.