Pharmacokinetic Evaluation of Metabolic Drug Interactions between Repaglinide and Celecoxib by a Bioanalytical HPLC Method for Their Simultaneous Determination with Fluorescence Detection
Since diabetes mellitus and osteoarthritis are highly prevalent diseases, combinations of antidiabetic agents like repaglinide (REP) and non-steroidal anti-inflammatory drugs (NSAID) like celecoxib (CEL) could be commonly used in clinical practice. In this study, a simple and sensitive bioanalytical...
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2019-08-01
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Online Access: | https://www.mdpi.com/1999-4923/11/8/382 |
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author | Dong-Gyun Han Jinsook Kwak Seong-Wook Seo Ji-Min Kim Jin-Wook Yoo Yunjin Jung Yun-Hee Lee Min-Soo Kim Young-Suk Jung Hwayoung Yun In-Soo Yoon |
author_facet | Dong-Gyun Han Jinsook Kwak Seong-Wook Seo Ji-Min Kim Jin-Wook Yoo Yunjin Jung Yun-Hee Lee Min-Soo Kim Young-Suk Jung Hwayoung Yun In-Soo Yoon |
author_sort | Dong-Gyun Han |
collection | DOAJ |
description | Since diabetes mellitus and osteoarthritis are highly prevalent diseases, combinations of antidiabetic agents like repaglinide (REP) and non-steroidal anti-inflammatory drugs (NSAID) like celecoxib (CEL) could be commonly used in clinical practice. In this study, a simple and sensitive bioanalytical HPLC method combined with fluorescence detector (HPLC-FL) was developed and fully validated for simultaneous quantification of REP and CEL. A simple protein precipitation procedure and reversed C18 column with an isocratic mobile phase (mixture of ACN and pH 6.0 phosphate buffer) were employed for sample preparation and chromatographic separation. The fluorescence detector was set at a single excitation/emission wavelength pair of 240 nm/380 nm. The linearity (10−2000 ng/mL), accuracy, precision, extraction recovery, matrix effect, and stability for this method were validated as per the current FDA guidance. The bioanalytical method was applied to study pharmacokinetic interactions between REP and CEL in vivo, successfully showing that concurrent administration with oral REP significantly altered the pharmacokinetics of oral CEL. Furthermore, an in vitro metabolism and protein binding study using human materials highlighted the possibility of metabolism-based interactions between CEL and REP in clinical settings. |
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issn | 1999-4923 |
language | English |
last_indexed | 2024-04-14T01:01:58Z |
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spelling | doaj.art-f4a535c138a24e82952aed10654f06bc2022-12-22T02:21:24ZengMDPI AGPharmaceutics1999-49232019-08-0111838210.3390/pharmaceutics11080382pharmaceutics11080382Pharmacokinetic Evaluation of Metabolic Drug Interactions between Repaglinide and Celecoxib by a Bioanalytical HPLC Method for Their Simultaneous Determination with Fluorescence DetectionDong-Gyun Han0Jinsook Kwak1Seong-Wook Seo2Ji-Min Kim3Jin-Wook Yoo4Yunjin Jung5Yun-Hee Lee6Min-Soo Kim7Young-Suk Jung8Hwayoung Yun9In-Soo Yoon10Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaDepartment of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaDepartment of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaDepartment of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaDepartment of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaDepartment of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaDepartment of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, KoreaDepartment of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaDepartment of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaDepartment of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaDepartment of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaSince diabetes mellitus and osteoarthritis are highly prevalent diseases, combinations of antidiabetic agents like repaglinide (REP) and non-steroidal anti-inflammatory drugs (NSAID) like celecoxib (CEL) could be commonly used in clinical practice. In this study, a simple and sensitive bioanalytical HPLC method combined with fluorescence detector (HPLC-FL) was developed and fully validated for simultaneous quantification of REP and CEL. A simple protein precipitation procedure and reversed C18 column with an isocratic mobile phase (mixture of ACN and pH 6.0 phosphate buffer) were employed for sample preparation and chromatographic separation. The fluorescence detector was set at a single excitation/emission wavelength pair of 240 nm/380 nm. The linearity (10−2000 ng/mL), accuracy, precision, extraction recovery, matrix effect, and stability for this method were validated as per the current FDA guidance. The bioanalytical method was applied to study pharmacokinetic interactions between REP and CEL in vivo, successfully showing that concurrent administration with oral REP significantly altered the pharmacokinetics of oral CEL. Furthermore, an in vitro metabolism and protein binding study using human materials highlighted the possibility of metabolism-based interactions between CEL and REP in clinical settings.https://www.mdpi.com/1999-4923/11/8/382celecoxibdrug–drug interactionfluorescenceHPLCmetabolismrepaglinide |
spellingShingle | Dong-Gyun Han Jinsook Kwak Seong-Wook Seo Ji-Min Kim Jin-Wook Yoo Yunjin Jung Yun-Hee Lee Min-Soo Kim Young-Suk Jung Hwayoung Yun In-Soo Yoon Pharmacokinetic Evaluation of Metabolic Drug Interactions between Repaglinide and Celecoxib by a Bioanalytical HPLC Method for Their Simultaneous Determination with Fluorescence Detection Pharmaceutics celecoxib drug–drug interaction fluorescence HPLC metabolism repaglinide |
title | Pharmacokinetic Evaluation of Metabolic Drug Interactions between Repaglinide and Celecoxib by a Bioanalytical HPLC Method for Their Simultaneous Determination with Fluorescence Detection |
title_full | Pharmacokinetic Evaluation of Metabolic Drug Interactions between Repaglinide and Celecoxib by a Bioanalytical HPLC Method for Their Simultaneous Determination with Fluorescence Detection |
title_fullStr | Pharmacokinetic Evaluation of Metabolic Drug Interactions between Repaglinide and Celecoxib by a Bioanalytical HPLC Method for Their Simultaneous Determination with Fluorescence Detection |
title_full_unstemmed | Pharmacokinetic Evaluation of Metabolic Drug Interactions between Repaglinide and Celecoxib by a Bioanalytical HPLC Method for Their Simultaneous Determination with Fluorescence Detection |
title_short | Pharmacokinetic Evaluation of Metabolic Drug Interactions between Repaglinide and Celecoxib by a Bioanalytical HPLC Method for Their Simultaneous Determination with Fluorescence Detection |
title_sort | pharmacokinetic evaluation of metabolic drug interactions between repaglinide and celecoxib by a bioanalytical hplc method for their simultaneous determination with fluorescence detection |
topic | celecoxib drug–drug interaction fluorescence HPLC metabolism repaglinide |
url | https://www.mdpi.com/1999-4923/11/8/382 |
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