Lack of the effect of lobeglitazone, a peroxisome proliferator-activated receptor-γ agonist, on the pharmacokinetics and pharmacodynamics of warfarin
Received 29 October 2014
Accepted for publication 12 December 2014
Published 2 March 2015 Volume 2015:9 Pages 737—743
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Prof. Dr. Wei Duan
Jin Ah Jung,1 Soo-Yun Lee,2 Tae-Eun Kim,3 Jung-Ryul Kim,1 Chin Kim,4 Wooseong Huh,1,5 Jae-Wook Ko1,2
1Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, 2Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, 3Department of Clinical Pharmacology, Konkuk University Medical Center, 4Clinical Research Team, CKD Pharmaceuticals, 5Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
Aims: 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 (Cmax) 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.
Conclusion: 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.
Keywords: lobeglitazone, thiazolidinedione, warfarin, pharmacokinetics, pharmacodynamics