title: Effects of renal impairment on the pharmacokinetics and pharmacodynamics of a novel dipeptidyl peptidase-4 inhibitor, evogliptin (DA-1229).
abstract: Evogliptin is a novel potent and selective dipeptidyl peptidase-4 (DPP-4) inhibitor. The aim of the present study was to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of evogliptin in participants with renal impairment (RI). An open-label, parallel-group clinical study was conducted in participants with mild, moderate and severe RI and in matched participants with normal renal function (NRF). A single oral 5-mg dose of evogliptin was administered and serial blood and urine samples were obtained to assess the PK and PD characteristics of evogliptin. Baseline urine samples were collected to evaluate endogenous CYP3A metabolic markers. The plasma exposure to evogliptin and degree of DPP-4 activity inhibition increased with decreasing renal function. The mean areas under the concentration-time curves from 0 to 120 hours were increased 1.2-, 1.8- and 1.98-fold in the mild, moderate and severe RI groups, respectively, compared with the NRF group. The levels of CYP3A metabolic markers were lower in the RI group than in the NRF group. 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.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: Jaeseong
authors.initials: J
authors.lastname: Oh
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: Andrew HyoungJin
authors.initials: AH
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: SeungHwan
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: Hyunjeong
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: Yon Su
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Product Development, Dong-A ST Co. Ltd, Seoul, Korea.
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Bahng
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: Seo Hyun
authors.initials: SH
authors.lastname: Yoon
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: Joo-Youn
authors.initials: JY
authors.lastname: Cho
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: In-Jin
authors.initials: IJ
authors.lastname: Jang
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: Kyung-Sang
authors.initials: KS
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D002853:Chromatography, Liquid; D003348:Cortisone / Q000031:analogs & derivatives / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000378:metabolism; D006888:Hydroxycholesterols / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D051436:Renal Insufficiency, Chronic / Q000378:metabolism*; D056910:Republic of Korea; D012720:Severity of Illness Index; D053719:Tandem Mass Spectrometry
chemical_list: C557982:4-(3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl)piperazin-2-one; C485511:6 beta-hydroxycortisone; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006888:Hydroxycholesterols; D010879:Piperazines; C099828:cholest-5-ene-3,4-diol; C001380:6 beta-hydroxycortisol; D051544:Cytochrome P-450 CYP3A; D018819:Dipeptidyl Peptidase 4; D003348:Cortisone; D006854:Hydrocortisone
keywords: 
  DPP-IV inhibitor; antidiabetic drug; drug development; pharmacodynamics; pharmacokinetics; phase I to II study