Effect of CYP2C9 polymorphisms on prescribed dose and time-to-stable dose of sulfonylureas in primary care patients with Type 2 diabetes mellitus.
OBJECTIVE
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 healthy individuals. In this study, the effect of CYP2C9*2 and CYP2C9*3 alleles on prescribed dose and time-to-stable dose of sulfonylureas was investigated.


METHODS
A group of 207 incident sulfonylurea users treated in four university affiliated primary care centers were identified. The effect of the CYP2C9*2 and CYP2C9*3 alleles on prescribed dose and time-to-stable dose was then assessed.


RESULTS
No significant effects of the CYP2C9*2 and CYP2C9*3 alleles were found. However, a trend towards a lower stable glimepiride dose for carriers of the CYP2C9*3 allele was observed.


CONCLUSIONS
Genotyping for the CYP2C9*2 and CYP2C9*3 alleles currently appears to have no clinical implications for dosing of sulfonylureas in primary care patients with Type 2 diabetes mellitus.
Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
Jesse J
JJ
Swen
Judith A M
JA
Wessels
Annemarie
A
Krabben
Willem J J
WJ
Assendelft
Henk-Jan
HJ
Guchelaar
D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001786:Blood Glucose / Q000032:analysis; D065729:Cytochrome P-450 CYP2C9; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D011307:Drug Prescriptions / Q000592:standards; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D009426:Netherlands; D011110:Polymorphism, Genetic; D011320:Primary Health Care / Q000592:standards; D012189:Retrospective Studies; D012463:Saliva / Q000201:enzymology; D013453:Sulfonylurea Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D013997:Time Factors
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases