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Loisios-Konstantinidis I, Cristofoletti R, Jamei M, et al. Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling to Predict the Impact of CYP2C9 Genetic Polymorphisms, Co-Medication and Formulation on the Pharmacokinetics and Pharmacodynamics of Flurbiprofen. Pharmaceutics. 2020;12(11)doi: 10.3390/pharmaceutics12111049.
Loisios-Konstantinidis, I., Cristofoletti, R., Jamei, M., Turner, D., & Dressman, J. (2020). Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling to Predict the Impact of CYP2C9 Genetic Polymorphisms, Co-Medication and Formulation on the Pharmacokinetics and Pharmacodynamics of Flurbiprofen. Pharmaceutics, 12(11), . https://doi.org/10.3390/pharmaceutics12111049
Loisios-Konstantinidis, Ioannis, et al. "Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling to Predict the Impact of CYP2C9 Genetic Polymorphisms, Co-Medication and Formulation on the Pharmacokinetics and Pharmacodynamics of Flurbiprofen." Pharmaceutics vol. 12,11 (2020). doi: https://doi.org/10.3390/pharmaceutics12111049
Loisios-Konstantinidis I, Cristofoletti R, Jamei M, Turner D, Dressman J. Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling to Predict the Impact of CYP2C9 Genetic Polymorphisms, Co-Medication and Formulation on the Pharmacokinetics and Pharmacodynamics of Flurbiprofen. Pharmaceutics. 2020 Nov 02;12(11). doi: 10.3390/pharmaceutics12111049. PMID: 33147873; PMCID: PMC7693160.
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Pharmaceutics. 2020 Nov 02;12(11). doi: 10.3390/pharmaceutics12111049.

Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling to Predict the Impact of CYP2C9 Genetic Polymorphisms, Co-Medication and Formulation on the Pharmacokinetics and Pharmacodynamics of Flurbiprofen.

Pharmaceutics

Ioannis Loisios-Konstantinidis, Rodrigo Cristofoletti, Masoud Jamei, David Turner, Jennifer Dressman

Affiliations

  1. Institute of Pharmaceutical Technology, Goethe University, Max-von-Laue str. 9, 60438 Frankfurt am Main, Germany.
  2. Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA.
  3. Certara UK Limited, Simcyp Division, 1 Concourse Way, Sheffield S1 2BJ, UK.
  4. Fraunhofer Institute of Translational Pharmacology and Medicine (ITMP), Carl-von-Noorden Platz 9, 60596 Frankfurt am Main, Germany.

PMID: 33147873 PMCID: PMC7693160 DOI: 10.3390/pharmaceutics12111049

Abstract

Physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models can serve as a powerful framework for predicting the influence as well as the interaction of formulation, genetic polymorphism and co-medication on the pharmacokinetics and pharmacodynamics of drug substances. In this study, flurbiprofen, a potent non-steroid anti-inflammatory drug, was chosen as a model drug. Flurbiprofen has absolute bioavailability of ~95% and linear pharmacokinetics in the dose range of 50-300 mg. Its absorption is considered variable and complex, often associated with double peak phenomena, and its pharmacokinetics are characterized by high inter-subject variability, mainly due to its metabolism by the polymorphic CYP2C9 (fmCYP2C9 ≥ 0.71). In this study, by leveraging

Keywords: drug–drug interaction (DDI); in vitro in vivo extrapolation (IVIVE); mechanistic oral absorption modeling; pharmacogenetics; pharmacokinetics/pharmacodynamics (PK/PD); physiologically based pharmacokinetic (PBPK) modeling

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