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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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2019-08-01
Series:Pharmaceutics
Subjects:
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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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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