Effects Of CYP2C19 Genetic Polymorphism On The Pharmacokinetics And Pharmacodynamics Of Omeprazole In Chinese Subjects

Background One of hot topics in pharmacogenomics and research of PPIs is the effects of CYP2C19 genetic polymorphism on the pharmacokinetics, pharmacodynamics and clinical efficacy. But the effect of CYP2C19 genetic differences in the metabolism of OPZ on intragastric pH in Chinese Han people has not been reported, and none of clinical investigation of healing effect of peptic ulcers treated by PPIs was seen.Objective To investigate the acid inhibitory effects and serum levels of omeprazole in Chinese Han healthy subjects, as well as the peptic ulcer healing effect of omeprazole versus other proton pump inhibitors evaluated endoscopically with reference to different CYP2C19 genotypes.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. All subjects were H. pylori-negative, which were determined by serology and ¹³C-urea breath test. After dl and d8 orally received omeprazole 20mg once daily in the morning, intragastric pH values were monitored for 24 hours by Digitrapper pH. Meanwhile, blood samples were collected at various time-point until 24 hours after administration. The serum concentrations of omeprazole were measured by high performance liquid chromatography.