Effect of renal impairment and haemodialysis on the pharmacokinetics of gemigliptin (LC15‐0444)

Abstract

This study evaluated the effects of renal impairment (RI) and haemodialysis (HD) on the pharmacokinetics of gemigliptin, a novel dipeptidyl peptidase-4 (DPP-4) inhibitor. After a 100 mg administration to subjects with normal renal function (n = 23) or RI (n = 24), plasma, urine or dialysate samples were analysed. Control subjects were matched to patients based on age, gender and body mass index. Patients with mild, moderate, severe RI and end-stage renal disease (ESRD) showed 1.20, 2.04, 1.50 and 1.66-fold (1.10, 1.49, 1.22 and 1.21-fold) increase of mean area under the time-plasma concentration curve from 0 to infinity (AUCinf) [maximum plasma concentration (Cmax)] of gemigliptin, respectively. Pharmacokinetics of gemigliptin was comparable between HD and non-HD periods in ESRD patients. Less than 4% of the dose was removed by 4 h HD. RI appeared to have modest effect on the gemigliptin disposition. No dose adjustment in patients with RI is proposed on the basis of exposure-response relationship. Impact of HD on the removal of gemigliptin was negligible.

Efficacy and safety of gemigliptin, a dipeptidyl peptidase‐4 inhibitor, in patients with type 2 diabetes mellitus inadequately controlled with combination treatment of metformin and sulphonylurea: a 24‐week, multicentre, randomized, double‐blind, placebo‐controlled study (TROICA study)

“…It has a long half‐life (17‐21 hours) and can be used in once‐daily regimen . The elimination of gemigliptin is balanced between urinary or faecal excretion and hepatic metabolism, and no dose adjustment is needed for renal impairment . Furthermore, gemigliptin has demonstrated efficacy as monotherapy and dual therapy with metformin …”

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

“…Renal impairment (RI), one of the complications of T2DM, can alter the PK and pharmacodynamic (PD) characteristics of DPP‐4 inhibitors, leading to requirements for dose adjustments of some agents . Notably, increasing attention has been focused on the use of DPP‐4 inhibitors to treat patients with T2DM with RI as a result of newly reported evidence of beneficial renal effects, even under non‐diabetic conditions .…”

Pharmacokinetics and Clinical Use of Incretin-Based Therapies in Patients with Chronic Kidney Disease and Type 2 Diabetes

“…Thus, CKD appeared to have a modest effect on the gemigliptin disposition and so no dose adjustment in patients with CKD is proposed on the basis of exposureresponse relationship. Impact of haemodialysis on the removal of gemigliptin was negligible [85].…”

“…In a study evaluating the effects of CKD and haemodialysis on the pharmacokinetics of gemigliptin (single dose of 100 mg) [85], patients with mild, moderate and severe CKD and ESRD showed 1.20, 2.04, 1.50 and 1.66-fold (1.69 for haemodialysed patients) increases of AUC ? , respectively, and 1.10, 1.49, 1.22 and 1.21-fold (1.25 for haemodialysed patients) increases of C max of gemigliptin, respectively ( Table 1).…”