The effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of glipizide in Chinese subjects.
OBJECTIVE
To study the effects of CYP2C9 and CYP2C19 genetic polymorphisms on the pharmacokinetics and pharmacodynamics of glipizide.


METHODS
Eighteen healthy male subjects were divided into three groups according to their genotypes: group I, CYP2C9*1/*1 and CYP2C19 extensive metabolizers (EMs); group II, CYP2C9*1/*1 and CYP2C19 poor metabolizers (PMs); and group III, CYP2C9*1/*3 and CYP2C19 EMs. After a single dose of a 5-mg glipizide tablet, plasma concentrations of glipizide for a 36-h period were determined. Meanwhile, plasma glucose levels and plasma insulin levels were determined from 0 to 4 h after dosing.


RESULTS
The area under the plasma concentration-time curve (AUC(0-infinity)) was 2.0-fold higher and the oral clearance was 51.1% lower in group III than in group I. The change in fasting insulin level within 1 h (DeltaAUEC(insulin0-1h)) in group III was 3.8-fold higher than that in group I. The glipizide parameters in group II exhibited similar tendencies to those in group III.


CONCLUSIONS
These results suggest that CYP2C9 polymorphism significantly influences the pharmacokinetics and pharmacodynamics of glipizide, which needs to be considered in clinical practice. CYP2C19 polymorphism exhibits a tendency to influence the effects of glipizide, to a certain extent similarly to CYP2C9 polymorphism.
Tan
Bo
B
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Zhang
Yi-Fan
YF
Chen
Xiao-Yan
XY
Zhao
Xiao-Hua
XH
Li
Guo-Xin
GX
Zhong
Da-Fang
DF
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001786:Blood Glucose / Q000032:analysis; D002681:China; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D005838:Genotype; D005913:Glipizide / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008297:Male; D008657:Metabolic Clearance Rate / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D013223:Statistics as Topic; D013997:Time Factors; D055815:Young Adult
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D005913:Glipizide