Effects of CYP2C19 genetic polymorphisms on PK/PD responses of omeprazole in Korean healthy volunteers

Sunny Park, Yang Jin Hyun, Yu Ran Kim, Ju Hyun Lee, Sunae Ryu, Jeong Mi Kim, Woo Yong Oh, Han Sung Na, Jong Gu Lee, Doo Won Seo, In Yeong Hwang, Zewon Park, In Jin Jang, Jaeseong Oh, Seung Eun Choi

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)729-736
Number of pages8
JournalJournal of Korean Medical Science
Volume32
Issue number5
DOIs
StatePublished - 1 May 2017

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Omeprazole
Genetic Polymorphisms
Healthy Volunteers
Pharmacokinetics
Stomach
Area Under Curve
National Institutes of Health (U.S.)
Tandem Mass Spectrometry
Liquid Chromatography
Single Nucleotide Polymorphism
Registries
Cytochrome P-450 CYP2C19
Genotype
Clinical Trials
Phenotype

Keywords

  • CYP2C19
  • Genetic polymorphisms
  • Omeprazole

Cite this

Park, Sunny ; Hyun, Yang Jin ; Kim, Yu Ran ; Lee, Ju Hyun ; Ryu, Sunae ; Kim, Jeong Mi ; Oh, Woo Yong ; Na, Han Sung ; Lee, Jong Gu ; Seo, Doo Won ; Hwang, In Yeong ; Park, Zewon ; Jang, In Jin ; Oh, Jaeseong ; Choi, Seung Eun. / Effects of CYP2C19 genetic polymorphisms on PK/PD responses of omeprazole in Korean healthy volunteers. In: Journal of Korean Medical Science. 2017 ; Vol. 32, No. 5. pp. 729-736.
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title = "Effects of CYP2C19 genetic polymorphisms on PK/PD responses of omeprazole in Korean healthy volunteers",
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.",
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author = "Sunny Park and Hyun, {Yang Jin} and Kim, {Yu Ran} and Lee, {Ju Hyun} and Sunae Ryu and Kim, {Jeong Mi} and Oh, {Woo Yong} and Na, {Han Sung} and Lee, {Jong Gu} and Seo, {Doo Won} and Hwang, {In Yeong} and Zewon Park and Jang, {In Jin} and Jaeseong Oh and Choi, {Seung Eun}",
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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 2017, 'Effects of CYP2C19 genetic polymorphisms on PK/PD responses of omeprazole in Korean healthy volunteers', Journal of Korean Medical Science, vol. 32, no. 5, pp. 729-736. https://doi.org/10.3346/jkms.2017.32.5.729

Effects of CYP2C19 genetic polymorphisms on PK/PD responses of omeprazole in Korean healthy volunteers. / Park, Sunny; Hyun, Yang Jin; Kim, Yu Ran; Lee, Ju Hyun; Ryu, Sunae; Kim, Jeong Mi; Oh, Woo Yong; Na, Han Sung; Lee, Jong Gu; Seo, Doo Won; Hwang, In Yeong; Park, Zewon; Jang, In Jin; Oh, Jaeseong; Choi, Seung Eun.

In: Journal of Korean Medical Science, Vol. 32, No. 5, 01.05.2017, p. 729-736.

Research output: Contribution to journalArticle

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T1 - Effects of CYP2C19 genetic polymorphisms on PK/PD responses of omeprazole in Korean healthy volunteers

AU - Park, Sunny

AU - Hyun, Yang Jin

AU - Kim, Yu Ran

AU - Lee, Ju Hyun

AU - Ryu, Sunae

AU - Kim, Jeong Mi

AU - Oh, Woo Yong

AU - Na, Han Sung

AU - Lee, Jong Gu

AU - Seo, Doo Won

AU - Hwang, In Yeong

AU - Park, Zewon

AU - Jang, In Jin

AU - Oh, Jaeseong

AU - Choi, Seung Eun

PY - 2017/5/1

Y1 - 2017/5/1

N2 - 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.

AB - 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.

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