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Open AccessArticle

Pharmacokinetic Evaluation of Metabolic Drug Interactions between Repaglinide and Celecoxib by a Bioanalytical HPLC Method for Their Simultaneous Determination with Fluorescence Detection

1
Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Korea
2
Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2019, 11(8), 382; https://doi.org/10.3390/pharmaceutics11080382
Received: 15 May 2019 / Revised: 26 July 2019 / Accepted: 29 July 2019 / Published: 2 August 2019
(This article belongs to the Special Issue Drug Metabolism/Transport and Pharmacokinetics)
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Abstract

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. View Full-Text
Keywords: celecoxib; drug–drug interaction; fluorescence; HPLC; metabolism; repaglinide celecoxib; drug–drug interaction; fluorescence; HPLC; metabolism; repaglinide
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Han, D.-G.; Kwak, J.; Seo, S.-W.; Kim, J.-M.; Yoo, J.-W.; Jung, Y.; Lee, Y.-H.; Kim, M.-S.; Jung, Y.-S.; Yun, H.; Yoon, I.-S. Pharmacokinetic Evaluation of Metabolic Drug Interactions between Repaglinide and Celecoxib by a Bioanalytical HPLC Method for Their Simultaneous Determination with Fluorescence Detection. Pharmaceutics 2019, 11, 382.

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