title: Evaluation of pharmacokinetic drug interactions between gemigliptin (dipeptidylpeptidase-4 inhibitor) and glimepiride (sulfonylurea) in healthy volunteers.
abstract: OBJECTIVE
  Gemigliptin is approved for the treatment of type II diabetes mellitus. Sulfonylureas are commonly used in combination with other antidiabetic drugs to improve glycemic control. The objective of this study was to evaluate the pharmacokinetics, safety, and tolerability of gemigliptin and glimepiride combination therapy compared with those of monotherapies.
  
  
  METHODS
  A randomized, open-label, crossover study was performed on healthy Korean male volunteers. Each subject received the following treatments (A and B) with a 7-day washout period: treatment A consisted of gemigliptin 50 mg once daily administered orally for 6 days, followed by concomitant oral dosing of glimepiride 4 mg and gemigliptin 50 mg on day 7; treatment B consisted of a single dose of glimepiride 4 mg. Blood samples were collected up to 24-h postdose on day 6 (gemigliptin) and day 7 (gemigliptin and glimepiride) following treatment A, and on day 1 (glimepiride) following treatment B. Concentrations of gemigliptin, glimepiride, and metabolites were determined using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). Safety assessments were performed throughout the study.
  
  
  RESULTS
  Twenty-three subjects completed the study. The geometric mean ratios (GMRs) of C max,ss and AUC τ,ss for gemigliptin were 1.0097 [90 % confidence interval (CI) 0.924-1.103] and 0.9997 (90 % CI 0.976-1.024), respectively. For glimepiride, the GMRs of C max and AUClast were 1.031 (90 % CI 0.908-1.172) and 0.995 (90 % CI 0.902-1.097), respectively. Both combination and monotherapy were well tolerated, and no serious adverse events were reported.
  
  
  CONCLUSIONS
  Gemigliptin and glimepiride did not alter the pharmacokinetic properties of each other when they were co-administered in healthy volunteers, and were generally tolerated.
authors: Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea.
authors: Hee Youn
authors: HY
authors: Choi
authors: Yo Han
authors: YH
authors: Kim
authors: Mi Jo
authors: MJ
authors: Kim
authors: Shi Hyang
authors: SH
authors: Lee
authors: Keunsu
authors: K
authors: Bang
authors: Song
authors: S
authors: Han
authors: Hyeong-Seok
authors: HS
authors: Lim
authors: Kyun-Seop
authors: KS
authors: Bae
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D002853:Chromatography, Liquid / Q000379:methods; D018592:Cross-Over Studies; D004347:Drug Interactions; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D010881:Piperidones / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D056910:Republic of Korea; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; C534891:LC15-0444; D010881:Piperidones; D011743:Pyrimidines; D013453:Sulfonylurea Compounds; C057619:glimepiride