title: Lack of the effect of lobeglitazone, a peroxisome proliferator-activated receptor-γ agonist, on the pharmacokinetics and pharmacodynamics of warfarin.
abstract: OBJECTIVE
  Lobeglitazone has been developed for the treatment of type 2 diabetes mellitus. This study was conducted to evaluate potential drug-drug interactions between lobeglitazone and warfarin, an anticoagulant with a narrow therapeutic index.
  
  
  METHODS
  In this open-label, three-treatment, crossover study, 24 healthy male subjects were administered lobeglitazone (0.5 mg) for 1-12 days with warfarin (25 mg) on day 5 in one period. After a washout interval, subjects were administered warfarin (25 mg) alone in the other period. Pharmacokinetics of R- and S-warfarin and lobeglitazone, as well as pharmacodynamics of warfarin, as measured by international normalized ratio (INR) and factor VII activity, were assessed.
  
  
  RESULTS
  The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for area under the curve from time zero to the time of the last quantifiable concentration (AUClast) for warfarin + lobeglitazone: warfarin alone were 1.0076 (90% CI: 0.9771, 1.0391) for R-warfarin and 0.9880 (90% CI: 0.9537, 1.0235) for S-warfarin. The maximum observed plasma concentration (C max) values were 1.0167 (90% CI: 0.9507, 1.0872) for R-warfarin and 1.0028 (90% CI: 0.9518, 1.0992) for S-warfarin, both of which were contained in the interval 0.80-1.25. Lobeglitazone had no effect on the area under the effect-time curve from time 0 to 168 hours (AUEC) of INR and factor VII activity, as demonstrated by the GMRs of 1.0091 (90% CI: 0.9872, 1.0314) and 0.9355 (90% CI: 0.9028, 0.9695), respectively. In addition, the pharmacokinetics of lobeglitazone was also unaffected by warfarin.
  
  
  CONCLUSIONS
  Concomitant administration of lobeglitazone and warfarin was well tolerated. Lobeglitazone had no meaningful effect on the pharmacokinetics or pharmacodynamics of warfarin. These findings indicate that lobeglitazone and warfarin can be coadministered without dosage adjustments for either drug.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Jin Ah
authors.initials: JA
authors.lastname: Jung
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Soo-Yun
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Clinical Pharmacology, Konkuk University Medical Center, Seoul, Republic of Korea.
authors.forename: Tae-Eun
authors.initials: TE
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Jung-Ryul
authors.initials: JR
authors.lastname: Kim
authors.affiliation: Clinical Research Team, CKD Pharmaceuticals, Seoul, Republic of Korea.
authors.forename: Chin
authors.initials: C
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea ; Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Wooseong
authors.initials: W
authors.lastname: Huh
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea ; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Ko
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004347:Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*; D014859:Warfarin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D011743:Pyrimidines; D045162:Thiazolidinediones; D014859:Warfarin; C546215:lobeglitazone
keywords: lobeglitazone; pharmacodynamics; pharmacokinetics; thiazolidinedione; warfarin