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

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 stu...

Full description

Saved in:
Bibliographic Details
Published in:European journal of clinical pharmacology 2011-08, Vol.67 (8), p.797-801
Main Authors: Surendiran, A., Pradhan, S. C., Agrawal, Aparna, Subrahmanyam, D. K. S., Rajan, S., Anichavezhi, D., Adithan, C.
Format: Article
Language:English
Subjects:
Alleles
Amplified Fragment Length Polymorphism Analysis
Aryl Hydrocarbon Hydroxylases - genetics
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cohort Studies
CYP2C9 gene
Cytochrome P-450 CYP2C9
Cytochrome P450
Diabetes
Diabetes mellitus
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - genetics
Diabetes Mellitus, Type 2 - metabolism
Diabetes. Impaired glucose tolerance
Drug Therapy, Combination
Drugs
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Enzymes
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Female
Gene polymorphism
Genetic Association Studies
Genotype & phenotype
glibenclamide
Glyburide - adverse effects
Glyburide - blood
Glyburide - pharmacokinetics
Glyburide - therapeutic use
Humans
Hyperglycemia - prevention & control
Hypoglycemia - chemically induced
Hypoglycemia - prevention & control
Hypoglycemic Agents - adverse effects
Hypoglycemic Agents - blood
Hypoglycemic Agents - pharmacokinetics
Hypoglycemic Agents - therapeutic use
India
Liquid chromatography
Male
Medical sciences
Metabolic Detoxication, Phase I
Metabolism
Metformin
Metformin - therapeutic use
Middle Aged
Pharmacogenetics
Pharmacology
Pharmacology. Drug treatments
Pharmacology/Toxicology
Plasma levels
Polymorphism
Polymorphism, Genetic
Pressure
Severity of Illness Index
Side effects
Statistical analysis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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  
ISSN:0031-6970
1432-1041
DOI:10.1007/s00228-011-1013-8