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Purpose: Omeprazole, a proton pump inhibitor (PPI), is used for the treatment of peptic ulcer, gastroesophageal reflux disease (GERD), and the eradication of Helicobacter pylori with antimicrobials. Omeprazole is extensively metabolized by cytochrome P450 enzymes, and CYP2C19 is the main metabolizing enzyme which is known to be highly polymorphic. It is reported that CYP2C19 genetic polymorphism can affects the pharmacokinetic and pharmacodynamic changes of several PPIs, including omeprazole. We studied the optimal dose adjustment of omeprazole in relation to CYP2C19 genotype.
Methods: Forty-two healthy Korean subjects were selected and they were divided into three groups according to CYP2C19 genotype, CYP2C19EM (CYP2C19*1/*1, n=15), CYP2C19IM (CYP2C19*1/*2 and CYP2C19*1/*3, n=15) and CYP2C19PM (CYP2C19*2/*2, CYP2C19*2/*3 and CYP2C19*3/*3, n=12) group. After overnight fasting, each genotype group received a single oral dose of 75, 60 and 20 mg omeprazole, respectively. Blood samples were collected up to 12 hr after drug intake, and plasma concentrations of omeprazole were determined by using LC-MS/MS system.
Results: Although the Cmax, t1/2 and CL/F were significantly different among three genotype groups (P<0.01, P<0.0001 and P<0.0001, respectively), AUCinf of omeprazole in each three group was not significantly different. These results indicates that overall plasma concentration of omeprazole in each group was similar.
Conclusion: Doses of omeprazole used in this study can be applied to the CYP2C19 genotype-based omeprazole dose determination in Koreans.