J Korean Med Sci.  2017 May;32(5):729-736. 10.3346/jkms.2017.32.5.729.

Effects of CYP2C19 Genetic Polymorphisms on PK/PD Responses of Omeprazole in Korean Healthy Volunteers

• Park S
• Hyun YJ
• Kim YR
• Lee JH
• Ryu S
• Kim JM
• Oh WY
• Na HS
• Lee JG
• Seo DW
• Hwang IY
• Park Z
• Jang IJ
• Oh J
• Choi SE

• KMID: 2375071
• DOI: http://doi.org/10.3346/jkms.2017.32.5.729

Abstract

The aim of this study was to examine the effects of CYP2C19*2 and *3 genetic polymorphisms on omeprazole pharmacokinetic (PK) and pharmacodynamic (PD) responses. Twenty-four healthy Korean volunteers were enrolled and given 20 mg omeprazole orally once daily for 8 days. The genotypes of CYP2C19 single nucleotide polymorphisms (SNPs) (*2, *3, and *17) were screened. The plasma concentrations of omeprazole, omeprazole sulfone, and 5-hydroxy (5-OH) omeprazole were determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The noncompartmental method was used for the determination of PK parameters. Change of mean pH and proportion (%) of time of gastric pH above 4.0 were estimated. The poor metabolizer (PM) group had the lowest metabolic ratio and exhibited the highest area under the curve (AUC) for omeprazole among the CYP2C19 phenotype groups. The PM group showed the greatest change of mean pH and the highest % time of gastric pH above 4.0. The relationship between AUC of omeprazole and % time of gastric pH above 4.0 was confirmed. The study demonstrates that CYP2C19*2 and *3 influence the PKs and PDs of omeprazole in Korean healthy volunteers. Clinical trial registry at the U.S. National Institutes of Health (https://clinicaltrials.gov), number NCT02299687.

Keyword

Omeprazole; CYP2C19; Genetic Polymorphisms

MeSH Terms

Area Under Curve
Chromatography, Liquid
Cytochrome P-450 CYP2C19*
Genotype
Healthy Volunteers*
Hydrogen-Ion Concentration
Methods
National Institutes of Health (U.S.)
Omeprazole*
Phenotype
Plasma
Polymorphism, Genetic*
Polymorphism, Single Nucleotide
Tandem Mass Spectrometry
Volunteers
Cytochrome P-450 CYP2C19
Omeprazole

Figure

• 

  Fig. 1 Metabolism of omeprazole.

• 

  Fig. 2 Trial profile. PM = poor metabolizer, IM = internal medicine, EM = emergency medicine.

• 

  Fig. 3 PK profiles of omeprazole and its metabolites in relation to CYP2C19 phenotypes. Plasma concentrations of omeprazole, 5-OH omeprazole, and omeprazole sulfone after single dosing (A, C, E), and multiple dosing (B, D, F). PK = pharmacokinetic, PM = poor metabolizer, IM = internal medicine, EM = emergency medicine.

• 

  Fig. 4 The correlation of omeprazole AUCinfinity and % time gastric pH above 4.0 after single (A) and multiple (B) dosing. AUCinfinity = area under the concentration time curve from 0 to infinity, PK = pharmacokinetic, PM = poor metabolizer, IM = internal medicine, EM = emergency medicine.

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