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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. The metabolism of omeprazole is primarily mediated by CYP2C19 enzyme and a lesser extent, CYP3A4. CYP2C19 is known as one of highly polymorphic drug metabolizing enzymes, so we investigated the effect of CYP2C19 genetic polymorphism on the pharmacokinetics and pharmacodymanics of omeprazole in healthy Koreans.
Methods: Thirty-nine healthy Korean subjects were selected and they were divided into three groups according to CYP2C19 genotype, CYP2C19EM (CYP2C19*1/*1, n=16), CYP2C19IM (CYP2C19*1/*2 and CYP2C19*1/*3, n=13), and CYP2C19PM (CYP2C19*2/*2, CYP2C19*2/*3, and CYP2C19*3/*3, n=10). After overnight fasting, each subject received a single oral dose of 40 mg omeprazole. Blood samples were collected up to 12 hr after drug intake, and the plasma concentrations of omeprazole was determined by using HPLC-UV system. Pharmacodynamics of omeprazole was evaluated by the measurement of intragastric pH.
Results: Cmax and AUCinf of omeprazole in CYP2C19PM group was significantly higher than that in CYP2C19EM and IM groups (both P<0.0001). Half-life (t1/2) and oral clearance (CL/F) of omeprazole were also significantly different between three genotype groups (both P<0.0001). The differences of mean pH, median pH and the fraction time pH>4 in each genotype group were all statistically significant (all P<0.0001).
Conclusion: CYP2C19 genetic polymorphisms affected the inhibition of gastric acid secretion by omeprazole.