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Influence of CYP2C9 gene polymorphisms on response to glibenclamide in type 2 diabetes mellitus patients

  • Pharmacogenetics
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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The antidiabetic drug glibenclamide is metabolized by the enzyme cytochrome P450 2C9 (CYP2C9) encoded by the polymorphic gene CYP2C9. Previous studies involving healthy volunteers have shown a significant influence of variant CYP2C9 genotypes on glibenclamide metabolism. The aim of this study was to investigate the influence of genetic polymorphisms of CYP2C9 on the response to glibenclamide and on glibenclamide plasma levels in type 2 diabetes mellitus patients.

Methods

The study cohort consisted of type 2 diabetes mellitus patients (n = 80) on regular therapy with glibenclamide either alone or with concomitant metformin. Plasma levels of glibenclamide were estimated by reverse phase high pressure liquid chromatography. The variant alleles of CYP2C9, namely CYP2C9 *2 and *3, were identified by PCR–restricted fragment length polymorphism. The plasma levels of glibenclamide and occurrences of hypoglycemic adverse effects with their severity were compared between the genotype groups.

Results

Of the 80 patients (61 males, 19 females), 78 were on concomitant treatment with two drugs, namely, glibenclamide and metformin, and two were on monotherapy with glibenclamide. There was a significant association (p < 0.001) between genotype status of CYP2C9 and the control of diabetes in patients receiving treatment with glibenclamide. There were no statistically significant differences in hypoglycemic adverse effects between the genotype groups.

Conclusion

The type 2 diabetes mellitus patients participating in this study with variant genotypes of CYP2C9 were found to respond better to treatment with glibenclamide than those with the normal genotype. The variant genotype CYP2C9 *1/*3 did not significantly influence the hypoglycemic adverse effects among those patients on long-term glibenclamide treatment.

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Acknowledgments

We gratefully acknowledge the Indian Council of Medical Research, New Delhi for funding this project (Sanction number: 53/17/2003-BMS. Dated 12.3.2007). We also acknowledge Dr. Jaideep Gogtay and Dr. SD Rajendran for providing pure powders of glibenclamide and glimepiride, respectively. We thank Ms. Indumathi, Ms Kayathri and Ms. Anuradha for their technical assistance in this project.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India

    A. Surendiran, S. C. Pradhan, S. Rajan, D. Anichavezhi & C. Adithan

  2. Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India

    Aparna Agrawal & D. K. S. Subrahmanyam

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  1. A. Surendiran
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  2. S. C. Pradhan
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  3. Aparna Agrawal
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  5. S. Rajan
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  6. D. Anichavezhi
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  7. C. Adithan
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Correspondence to A. Surendiran.

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Surendiran, A., Pradhan, S.C., Agrawal, A. et al. Influence of CYP2C9 gene polymorphisms on response to glibenclamide in type 2 diabetes mellitus patients. Eur J Clin Pharmacol 67, 797–801 (2011). https://doi.org/10.1007/s00228-011-1013-8

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  • DOI: https://doi.org/10.1007/s00228-011-1013-8

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