title: Evaluation of the pharmacokinetics of the DPP-4 inhibitor gemigliptin when coadministered with rosuvastatin or irbesartan to healthy subjects.
abstract: OBJECTIVE
  Gemigliptin is a selective DPP4 inhibitor used to treat type 2 diabetes. The objective of this study was to evaluate the pharmacokinetics (PKs) of gemigliptin, rosuvastatin, and irbesartan monotherapies and combination therapies.
  
  
  METHODS
  Randomized, open-label, three-treatment, six-sequence, three-period, crossover studies were performed on healthy male volunteers. The three treatments were: 50 mg gemigliptin alone; 20 mg rosuvastatin (part A) or 300 mg irbesartan alone (part B); and rosuvastatin or irbesartan with concomitant gemigliptin. Each drug was administered as part of once daily, 7 day, repeated dosing regimens with a 14 day washout period.
  
  
  BACKGROUND
  NCT01823133 (part A) and NCT01825850 (part B).
  
  
  METHODS
  The primary PK parameters - Cmax and AUCτ - were compared to the geometric mean ratios (GMRs) and 90% confidence intervals (90% CIs) that were determined for the combination therapies and monotherapies.
  
  
  RESULTS
  A total of 60 participants were administered the study drugs, and 52 participants (27 participants in part A; 25 participants in part B) were analyzed as part of the PK dataset. In part A, the GMRs (gemigliptin + rosuvastatin/gemigliptin) of the Cmax and AUCτ values of gemigliptin were 0.955 (90% CI = 0.874-1.044) and 1.023 (90% CI = 0.991-1.057), and those of rosuvastatin were 1.012 (90% CI = 0.946-1.084) and 1.086 (90% CI = 1.032-1.142), respectively. In part B, the GMRs of the Cmax and AUCτ values of gemigliptin were 1.046 (90% CI = 0.964-1.134) and 1.035 (90% CI = 1.005-1.065), and those of irbesartan were 0.966 (90% CI = 0.897-1.040) and 1.050 (90% CI = 0.993-1.111), respectively. The limitations of this study include its relatively short treatment period and small sample size, as only healthy participants were included.
  
  
  CONCLUSIONS
  Gemigliptin does not affect the PK properties of rosuvastatin or irbesartan; also, rosuvastatin and irbesartan do not affect the PKs of gemigliptin.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine , Seoul , Korea.
authors.forename: Hee Youn
authors.initials: HY
authors.lastname: Choi
authors.forename: Hyeong-Seok
authors.initials: HS
authors.lastname: Lim
authors.forename: Yo Han
authors.initials: YH
authors.lastname: Kim
authors.forename: Hae Sun
authors.initials: HS
authors.lastname: Jeon
authors.forename: Mi Jo
authors.initials: MJ
authors.lastname: Kim
authors.forename: Shi Hyang
authors.initials: SH
authors.lastname: Lee
authors.forename: Jong Hyuk
authors.initials: JH
authors.lastname: Jung
authors.forename: Young Kyoung
authors.initials: YK
authors.lastname: Lee
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Kyun-Seop
authors.initials: KS
authors.lastname: Bae
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001713:Biphenyl Compounds / Q000493:pharmacokinetics*; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005464:Fluorobenzenes / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D010881:Piperidones / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000493:pharmacokinetics*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000493:pharmacokinetics*; D013777:Tetrazoles / Q000493:pharmacokinetics*
chemical_list: D001713:Biphenyl Compounds; D001786:Blood Glucose; D005464:Fluorobenzenes; D007004:Hypoglycemic Agents; C534891:LC15-0444; D010881:Piperidones; D011743:Pyrimidines; D013449:Sulfonamides; D013777:Tetrazoles; D000068718:Rosuvastatin Calcium; D000077405:Irbesartan
keywords: Drug interactions; Irbesartan; LC15-0444; Pharmacokinetics; Rosuvastatin