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.
authors.affiliation: Clinical Research Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Korea.
authors.forename: Sunny
authors.identifier: 0000-0001-9053-6930
authors.initials: S
authors.lastname: Park
authors.affiliation: Clinical Research Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Korea.
authors.forename: Yang Jin
authors.initials: YJ
authors.lastname: Hyun
authors.affiliation: Clinical Research Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Korea.
authors.forename: Yu Ran
authors.initials: YR
authors.lastname: Kim
authors.affiliation: Clinical Research Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Korea.
authors.forename: Ju Hyun
authors.identifier: 0000-0001-8623-0744
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Clinical Research Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Korea.
authors.forename: Sunae
authors.identifier: 0000-0002-3817-2081
authors.initials: S
authors.lastname: Ryu
authors.affiliation: Clinical Research Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Korea.
authors.forename: Jeong Mi
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Clinical Research Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Korea.
authors.forename: Woo Yong
authors.identifier: 0000-0001-7442-7128
authors.initials: WY
authors.lastname: Oh
authors.affiliation: Clinical Research Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Korea.
authors.forename: Han Sung
authors.initials: HS
authors.lastname: Na
authors.affiliation: Clinical Research Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Korea.
authors.forename: Jong Gu
authors.identifier: 0000-0002-0282-8720
authors.initials: JG
authors.lastname: Lee
authors.affiliation: Clinical Research Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Korea.
authors.forename: Doo Won
authors.identifier: 0000-0002-9195-9975
authors.initials: DW
authors.lastname: Seo
authors.affiliation: Clinical Research Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Korea.
authors.forename: In Yeong
authors.identifier: 0000-0003-2377-5573
authors.initials: IY
authors.lastname: Hwang
authors.affiliation: Clinical Research Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Korea.
authors.forename: Zewon
authors.identifier: 0000-0001-9385-8396
authors.initials: Z
authors.lastname: Park
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: In Jin
authors.identifier: 0000-0002-8384-3139
authors.initials: IJ
authors.lastname: Jang
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
authors.forename: Jaeseong
authors.identifier: 0000-0001-6275-8587
authors.initials: J
authors.lastname: Oh
authors.affiliation: Clinical Research Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju, Korea. choi77@korea.kr.
authors.forename: Seung Eun
authors.identifier: 0000-0003-2922-9207
authors.initials: SE
authors.lastname: Choi
mesh_terms: D000328:Adult; D000897:Anti-Ulcer Agents / Q000032:analysis / Q000378:metabolism* / Q000493:pharmacokinetics; D019540:Area Under Curve; D044466:Asian People / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics / Q000378:metabolism*; D005745:Gastric Acidity Determination; D005838:Genotype; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D009853:Omeprazole / Q000032:analysis / Q000378:metabolism* / Q000493:pharmacokinetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; D056910:Republic of Korea; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D000897:Anti-Ulcer Agents; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole
keywords: CYP2C19; Genetic Polymorphisms; Omeprazole