Effects of CYP2C19 genetic polymorphism on the pharmacokinetics and pharmacodynamics of omeprazole in Chinese people.
BACKGROUND
To investigate whether the pharmacodynamics and pharmacokinetics of omeprazole (OPZ) are dependent of the CYP2C19 genotype status in Chinese people.


METHODS
Eighteen healthy subjects were voluntary to participate in the study, whose CYP2C19 genotype status were determined by polymerase chain reaction-restriction fragment length polymorphism method. There were six homozygous extensive metabolizers, six heterozygous extensive metabolizers and six poor metabolizers (PMs). All subjects were Helicobacter pylori-negative, determined by serology method and (13)C-urea breath test. After d1 and d8 orally received OPZ 20 mg once daily in the morning, intragastric pH values were monitored for 24 h by Digitrapper pH. Meanwhile, blood samples were collected at various time-points until 24 h after administration. The serum concentrations of OPZ were measured by liquid chromatography.


RESULTS
After single or repeated doses, the PMs showed a significantly higher mean area under the serum concentration-time curves (AUC) values than that observed in the homozygous extensive metabolizers or the heterozygous extensive metabolizers, with a relative ratio of 1.0 : 1.1 : 4.2 and 1.0 : 1.3 : 3.3 (homozygous extensive metabolizers:heterozygous extensive metabolizers:poor metabolizers), respectively. After a single dose of OPZ, significant differences in intragastric pH median, pH > 3 holding time and pH > 4 holding time were observed among the three groups. After repeated doses, the PMs showed a significantly higher intragastric pH values than that observed in the homozygous extensive metabolizers or the heterozygous extensive metabolizers.


CONCLUSIONS
The pharmacodynamic effects of OPZ and its pharmacokinetics depend on the CYP2C19 genotype status in Chinese people.
Hu
Xiang-Peng
XP
Center of Endoscopic Diagnosis and Therapy, First Affiliated Hospital of Wenzhou Medical College, Wenzhou [corrected] China.
Xu
Jian-Ming
JM
Hu
Yong-Mei
YM
Mei
Qiao
Q
Xu
Xin-Hua
XH
D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People; D002681:China; D065731:Cytochrome P-450 CYP2C19; D005744:Gastric Acid / Q000378:metabolism; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009853:Omeprazole / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
D000897:Anti-Ulcer Agents; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole