Effects of CYP2C19 genetic polymorphism on the pharmacokinetics and pharmacodynamics of omeprazole in Chinese people

• Published in: Journal of clinical pharmacy and therapeutics Vol. 32; no. 5; pp. 517 - 524
• Main Authors: Hu, Xiang-peng, Xu, Jian-ming, Hu, Yong-mei, Mei, Qiao, Xu, Xin-hua
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2007; Blackwell
• Subjects: Anti-Ulcer Agents - administration & dosage; Anti-Ulcer Agents - pharmacokinetics; Anti-Ulcer Agents - pharmacology; Area Under Curve; Aryl Hydrocarbon Hydroxylases - genetics; Asian Continental Ancestry Group; Biological and medical sciences; China; CYP2C19; Cytochrome P-450 CYP2C19; Gastric Acid - metabolism; genetic polymorphism; Genotype; Helicobacter; Heterozygote; Homozygote; Humans; Hydrogen-Ion Concentration; Male; Medical sciences; Mixed Function Oxygenases - genetics; omeprazole; Omeprazole - administration & dosage; Omeprazole - pharmacokinetics; Omeprazole - pharmacology; pharmacodynamics; pharmacokinetics; Pharmacology. Drug treatments; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Asia; China; Pharmacokinetic pharmacodynamic relationship; Pharmacodynamics; Genetic variability; Enzyme; Isozyme; Cytochrome P450; H; Enzyme inhibitor; Genotype; Antiulcer agent; K; CYP2C19; Biological activity; Proton pump inhibitor; Omeprazole; Benzimidazole derivatives; Antisecretory agent; exchanging ATPase; Hydrolases; Chinese; Pharmacokinetics; genetic polymorphism
• ISSN: 0269-4727; 1365-2710
• DOI: 10.1111/j.1365-2710.2007.00851.x

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 13C‐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. Conclusion:  The pharmacodynamic effects of OPZ and its pharmacokinetics depend on the CYP2C19 genotype status in Chinese people.