PII-073 - PHARMACOKINETICS AND PHARMACODYNAMICS OF EVOGLIPTIN IN END-STAGE RENAL DISEASE PATIENTS ON HEMODIALYSIS.

B. Kim¹, K. Yu¹, S. Lee¹, J. Oh², I. Jang²; ¹Seoul National University Bundang Hospital, Seoul, Republic of Korea, ²Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.

Background: Evogliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor for the treatment of type 2 diabetes. This study aimed to investigate the possible effect of hemodialysis (HD) on the pharmacokinetics (PK) and pharmacodynamics (PD) of evogliptin.

Methods: A single dose, open-label, parallel-group study was conducted in eight end-stage renal disease (ESRD) patients and eight matched healthy subjects. ESRD patients received a single oral dose of evogliptin 5 mg after and before HD with 2 week of washout in-between each dose, and healthy subjects received a single oral dose of evogliptin 5 mg. Serial blood and urine samples were collected over 48 hours to assess the PK and PD profiles of evogliptin. To compare PK parameters before and after HD, geometric mean ratios (GMRs) and its 90% confidence intervals (CIs) were calculated.

Results: The effect of HD on PK and PD of evogliptin was not clinically significant. The GMR and its 90% CI for maximum concentration (Cmax) and area under the concentration–time curve from time 0 to the last measurable timepoint (AUClast) of evogliptin before HD compared to after HD were 0.7293 (0.6171 - 0.8620) and 0.9480 (0.8162 - 1.1010), respectively. The results of maximum DPP-4 inhibitory effect (Emax), area under the DPP-4 inhibitory effect-time curve (AUEClast), and time duration of more than 80% DPP-4 inhibition (Fi80) were also comparable before and after HD. Compared to healthy subjects, the mean AUClast of evogliptin was 1.3- to 1.4-fold greater in ESRD patients, but the difference is unlikely to affect the safety and efficacy profiles of evogliptin.

Conclusion: The systemic exposure of evogliptin and the DPP-4 inhibitory effect were consistent in ESRD patients regardless of the effect of HD, thereby dose adjustment will not be required due to the HD status.