Lack of the effect of lobeglitazone, a peroxisome proliferator-activated receptor-γ agonist, on the pharmacokinetics and pharmacodynamics of warfarin
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, Sungkyunkw...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2015-03-01
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| Series: | Drug Design, Development and Therapy |
| Online Access: | http://www.dovepress.com/lack-of-the-effect-of-lobeglitazone-a-peroxisome-proliferator-activate-peer-reviewed-article-DDDT |
| _version_ | 1818752445112647680 |
|---|---|
| author | Jung JA Lee SY Kim TE Kim JR Kim C Huh W Ko JW |
| author_facet | Jung JA Lee SY Kim TE Kim JR Kim C Huh W Ko JW |
| author_sort | Jung JA |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-12-18T04:51:34Z |
| format | Article |
| id | doaj.art-d728d8d13b1644e8bd5530d031f0ed7c |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-18T04:51:34Z |
| publishDate | 2015-03-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-d728d8d13b1644e8bd5530d031f0ed7c2022-12-21T21:20:25ZengDove Medical PressDrug Design, Development and Therapy1177-88812015-03-012015default73774320689Lack of the effect of lobeglitazone, a peroxisome proliferator-activated receptor-γ agonist, on the pharmacokinetics and pharmacodynamics of warfarinJung JALee SYKim TEKim JRKim CHuh WKo JWJin 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, pharma­codynamicshttp://www.dovepress.com/lack-of-the-effect-of-lobeglitazone-a-peroxisome-proliferator-activate-peer-reviewed-article-DDDT |
| spellingShingle | Jung JA Lee SY Kim TE Kim JR Kim C Huh W Ko JW Lack of the effect of lobeglitazone, a peroxisome proliferator-activated receptor-γ agonist, on the pharmacokinetics and pharmacodynamics of warfarin Drug Design, Development and Therapy |
| title | Lack of the effect of lobeglitazone, a peroxisome proliferator-activated receptor-γ agonist, on the pharmacokinetics and pharmacodynamics of warfarin |
| title_full | Lack of the effect of lobeglitazone, a peroxisome proliferator-activated receptor-γ agonist, on the pharmacokinetics and pharmacodynamics of warfarin |
| title_fullStr | Lack of the effect of lobeglitazone, a peroxisome proliferator-activated receptor-γ agonist, on the pharmacokinetics and pharmacodynamics of warfarin |
| title_full_unstemmed | Lack of the effect of lobeglitazone, a peroxisome proliferator-activated receptor-γ agonist, on the pharmacokinetics and pharmacodynamics of warfarin |
| title_short | Lack of the effect of lobeglitazone, a peroxisome proliferator-activated receptor-γ agonist, on the pharmacokinetics and pharmacodynamics of warfarin |
| title_sort | lack of the effect of lobeglitazone a peroxisome proliferator activated receptor gamma agonist on the pharmacokinetics and pharmacodynamics of warfarin |
| url | http://www.dovepress.com/lack-of-the-effect-of-lobeglitazone-a-peroxisome-proliferator-activate-peer-reviewed-article-DDDT |
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