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Drug Metabolism and Personalized Therapy

Official journal of the European Society of Pharmacogenomics and Personalised Therapy

Editor-in-Chief: Llerena, Adrián

Editorial Board: Benjeddou, Mongi / Chen, Bing / Dahl, Marja-Liisa / Devinsky, Ferdinand / Hirata, Rosario / Hubacek, Jaroslav A. / Ingelman-Sundberg, Magnus / Maitland-van der Zee, Anke-Hilse / Manolopoulos, Vangelis G. / Marc, Janja / Melichar, Bohuslav / Meyer, Urs A. / Nair, Sujit / Nofziger, Charity / Peiro, Ana / Sadee, Wolfgang / Salazar, Luis A. / Simmaco, Maurizio / Turpeinen, Miia / Schaik, Ron / Shin, Jae-Gook / Visvikis-Siest, Sophie / Zanger, Ulrich M.


CiteScore 2018: 1.01

SCImago Journal Rank (SJR) 2018: 0.277
Source Normalized Impact per Paper (SNIP) 2018: 0.446

Online
ISSN
2363-8915
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Volume 26, Issue 2

Issues

Stereoselective binding of chiral anti-diabetic drug nateglinide to plasma proteins

Srinivas Maddi
  • Department of Pharmaceutical Chemistry, Friedrich Schiller University, Jena, Germany
  • Biopharmaceutics and Pharmacokinetics Laboratory, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, India
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/ Gerhard Scriba / Madhusudan Rao Yamsani
  • Biopharmaceutics and Pharmacokinetics Laboratory, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, India
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Published Online: 2011-07-06 | DOI: https://doi.org/10.1515/dmdi.2011.004

Abstract

The binding of nateglinide (NA) enantiomers with human plasma (HP), human serum albumin (HSA) and bovine serum albumin (BSA) was investigated. The protein binding was studied over a drug concentration range of 5–100 μM at a protein concentration of 600 μM. Unbound drug concentrations were determined by direct chiral liquid chromatography using chiralcel OJ-RH column. At therapeutic drug concentrations, the protein binding of each enantiomer was >98%. The results showed that the binding of NA enantiomers was stereoselective, mutually competitive and non-linear. The binding characteristics were, however, opposite for the two most important plasma binding proteins. Opposite stereo-selectivity was observed between BSA and HSA while stereo-selectivity was identical between HSA and HP. Scatchard analysis was used to illustrate the different binding affinities of NA enantiomers to BSA, HSA and HP. The interaction between enantiomers observed in HP and serum albumins was confirmed as a competitive type interaction at the high affinity site. Scatchard analysis was used to illustrate the different binding affinities of NA enantiomers to BSA, HSA and HP.

Keywords: enantiomer; nateglinide; plasma protein binding

About the article

Corresponding author: Srinivas Maddi, Research Investigator, Metabolism and Pharmacokinetics, Pharmaceutical Candidate Optimization, Biocon-Bristol Meyers Squibb R&D Centre, Syngene International Ltd., Bangalore 560100, India


Received: 2011-02-15

Accepted: 2011-05-09

Published Online: 2011-07-06

Published in Print: 2011-08-01


Citation Information: Drug Metabolism and Drug Interactions, Volume 26, Issue 2, Pages 81–86, ISSN (Online) 2191-0162, ISSN (Print) 0792-5077, DOI: https://doi.org/10.1515/dmdi.2011.004.

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