Effect of CYP2C9 polymorphisms on prescribed dose and time-to-stable dose of sulfonylureas in primary care patients with Type 2 diabetes mellitus

• Published in: Pharmacogenomics Vol. 11; no. 11; pp. 1517 - 1523
• Main Authors: Swen, Jesse J, Wessels, Judith A M, Krabben, Annemarie, Assendelft, Willem J J, Guchelaar, Henk-Jan
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.11.2010
• Subjects: Alleles; Aryl Hydrocarbon Hydroxylases - genetics; Blood Glucose - analysis; Cytochrome P-450; Cytochrome P-450 CYP2C9; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - enzymology; Diabetes Mellitus, Type 2 - genetics; Diabetes therapy; Dose-Response Relationship, Drug; Drug Prescriptions - standards; Female; Genetic aspects; Genetic Testing; Genotype; Glimepiride; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - pharmacokinetics; Hypoglycemic Agents - therapeutic use; Kaplan-Meier Estimate; Male; Medical Records; Middle Aged; Netherlands; Polymorphism, Genetic; Primary Health Care - standards; Retrospective Studies; Saliva - enzymology; Sulfonylurea Compounds - administration & dosage; Sulfonylurea Compounds - pharmacokinetics; Sulfonylurea Compounds - therapeutic use; Time Factors; Type 2 diabetes; Netherlands

Sulfonylureas are mainly metabolized by the enzyme CYP2C9. Two allelic variants, CYP2C9*2 and CYP2C9*3, result in decreased metabolic capacity and have been associated with elevated sulfonylurea serum levels. However, most of the available data originates from pharmacokinetic analyses performed in h...