Stereospecific analysis of omeprazole in human plasma as a probe for CYP2C19 phenotype

Hideko Kanazawa, Akiko Okada, Megumu Higaki, Hiromitsu Yokota, Fumiko Mashige, Kazuhiko Nakahara

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Omeprazole is a class referred to as proton pump inhibitor; it acts to regulate acid production in the stomach and is used to treat various acid-related gastrointestinal disorders. In the liver, it is metabolized to varying degrees by several cytochrome P-450 (CYP) isoenzymes which are further categorized into subfamilies of related polymorphic gene products. The metabolism of omeprazole is to a large extent dependent on CYP3A4 and CYP2C19. Omeprazole is metabolized to two major metabolites, 5-hydroxyomeprazole (CYP2C19) and omeprazole sulfone (CYP3A4). Minor mutations in CYP2C19 affect its activity in the liver and, in turn, the metabolic and pharmacokinetic profiles of omeprazole. The frequency of CYP2C19 poor metabolizers in population of Asian descent has been reported to range from 10 to 20%. Accordingly, results from population studies indicate that omeprazole can be used as a probe drug for phenotyping CYP2C19. The optical isomers of omeprazole show a clear difference in their metabolism by human liver microsomes. This study demonstrates the stereospecific analysis of omeprazole in human plasma as a probe drug of CYP2C19 phenotyping. The chiral separation of omeprazole was achieved on a chiral column with circular dichroism (CD) detection and LC/MS. A good resolution of enantiomers was obtained. The column used for chiral separation was CHIRALPAK AD-RH column (4.6×150 mm) using phosphate buffer and (or ammonium acetate) acetonitrile as an eluent. After a single oral dose of omeprazole (20 mg), the plasma concentrations of the separate enantiomers of omeprazole were determined for 3.5 h after drug intake. The present study is useful because of the part polymorphism plays in the therapeutic effectiveness of proton pump inhibitors during the treatment of acid-related diseases.

Original languageEnglish
Pages (from-to)1817-1824
Number of pages8
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume30
Issue number6
DOIs
Publication statusPublished - 2003 Jan 15

Fingerprint

Plasma (human)
Omeprazole
Phenotype
Liver
Cytochrome P-450 CYP3A
Enantiomers
Proton Pump Inhibitors
Metabolism
Acids
Cytochrome P-450 CYP2C19
Pharmaceutical Preparations
Pharmacokinetics
Metabolome
Liver Microsomes
Metabolites
Circular Dichroism
Polymorphism
Isomers
Cytochrome P-450 Enzyme System
Population

Keywords

  • Circular dichroism detection
  • CYP2C19
  • Cytochrome P-450
  • LC/MS
  • Omeprazole
  • Proton pump inhibitor
  • Stereospecific analysis

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science

Cite this

Stereospecific analysis of omeprazole in human plasma as a probe for CYP2C19 phenotype. / Kanazawa, Hideko; Okada, Akiko; Higaki, Megumu; Yokota, Hiromitsu; Mashige, Fumiko; Nakahara, Kazuhiko.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 30, No. 6, 15.01.2003, p. 1817-1824.

Research output: Contribution to journalArticle

Kanazawa, Hideko ; Okada, Akiko ; Higaki, Megumu ; Yokota, Hiromitsu ; Mashige, Fumiko ; Nakahara, Kazuhiko. / Stereospecific analysis of omeprazole in human plasma as a probe for CYP2C19 phenotype. In: Journal of Pharmaceutical and Biomedical Analysis. 2003 ; Vol. 30, No. 6. pp. 1817-1824.
@article{6b49cde83fe7460ab2e73e2c3728eb27,
title = "Stereospecific analysis of omeprazole in human plasma as a probe for CYP2C19 phenotype",
abstract = "Omeprazole is a class referred to as proton pump inhibitor; it acts to regulate acid production in the stomach and is used to treat various acid-related gastrointestinal disorders. In the liver, it is metabolized to varying degrees by several cytochrome P-450 (CYP) isoenzymes which are further categorized into subfamilies of related polymorphic gene products. The metabolism of omeprazole is to a large extent dependent on CYP3A4 and CYP2C19. Omeprazole is metabolized to two major metabolites, 5-hydroxyomeprazole (CYP2C19) and omeprazole sulfone (CYP3A4). Minor mutations in CYP2C19 affect its activity in the liver and, in turn, the metabolic and pharmacokinetic profiles of omeprazole. The frequency of CYP2C19 poor metabolizers in population of Asian descent has been reported to range from 10 to 20{\%}. Accordingly, results from population studies indicate that omeprazole can be used as a probe drug for phenotyping CYP2C19. The optical isomers of omeprazole show a clear difference in their metabolism by human liver microsomes. This study demonstrates the stereospecific analysis of omeprazole in human plasma as a probe drug of CYP2C19 phenotyping. The chiral separation of omeprazole was achieved on a chiral column with circular dichroism (CD) detection and LC/MS. A good resolution of enantiomers was obtained. The column used for chiral separation was CHIRALPAK AD-RH column (4.6×150 mm) using phosphate buffer and (or ammonium acetate) acetonitrile as an eluent. After a single oral dose of omeprazole (20 mg), the plasma concentrations of the separate enantiomers of omeprazole were determined for 3.5 h after drug intake. The present study is useful because of the part polymorphism plays in the therapeutic effectiveness of proton pump inhibitors during the treatment of acid-related diseases.",
keywords = "Circular dichroism detection, CYP2C19, Cytochrome P-450, LC/MS, Omeprazole, Proton pump inhibitor, Stereospecific analysis",
author = "Hideko Kanazawa and Akiko Okada and Megumu Higaki and Hiromitsu Yokota and Fumiko Mashige and Kazuhiko Nakahara",
year = "2003",
month = "1",
day = "15",
doi = "10.1016/S0731-7085(02)00524-1",
language = "English",
volume = "30",
pages = "1817--1824",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
issn = "0731-7085",
publisher = "Elsevier",
number = "6",

}

TY - JOUR

T1 - Stereospecific analysis of omeprazole in human plasma as a probe for CYP2C19 phenotype

AU - Kanazawa, Hideko

AU - Okada, Akiko

AU - Higaki, Megumu

AU - Yokota, Hiromitsu

AU - Mashige, Fumiko

AU - Nakahara, Kazuhiko

PY - 2003/1/15

Y1 - 2003/1/15

N2 - Omeprazole is a class referred to as proton pump inhibitor; it acts to regulate acid production in the stomach and is used to treat various acid-related gastrointestinal disorders. In the liver, it is metabolized to varying degrees by several cytochrome P-450 (CYP) isoenzymes which are further categorized into subfamilies of related polymorphic gene products. The metabolism of omeprazole is to a large extent dependent on CYP3A4 and CYP2C19. Omeprazole is metabolized to two major metabolites, 5-hydroxyomeprazole (CYP2C19) and omeprazole sulfone (CYP3A4). Minor mutations in CYP2C19 affect its activity in the liver and, in turn, the metabolic and pharmacokinetic profiles of omeprazole. The frequency of CYP2C19 poor metabolizers in population of Asian descent has been reported to range from 10 to 20%. Accordingly, results from population studies indicate that omeprazole can be used as a probe drug for phenotyping CYP2C19. The optical isomers of omeprazole show a clear difference in their metabolism by human liver microsomes. This study demonstrates the stereospecific analysis of omeprazole in human plasma as a probe drug of CYP2C19 phenotyping. The chiral separation of omeprazole was achieved on a chiral column with circular dichroism (CD) detection and LC/MS. A good resolution of enantiomers was obtained. The column used for chiral separation was CHIRALPAK AD-RH column (4.6×150 mm) using phosphate buffer and (or ammonium acetate) acetonitrile as an eluent. After a single oral dose of omeprazole (20 mg), the plasma concentrations of the separate enantiomers of omeprazole were determined for 3.5 h after drug intake. The present study is useful because of the part polymorphism plays in the therapeutic effectiveness of proton pump inhibitors during the treatment of acid-related diseases.

AB - Omeprazole is a class referred to as proton pump inhibitor; it acts to regulate acid production in the stomach and is used to treat various acid-related gastrointestinal disorders. In the liver, it is metabolized to varying degrees by several cytochrome P-450 (CYP) isoenzymes which are further categorized into subfamilies of related polymorphic gene products. The metabolism of omeprazole is to a large extent dependent on CYP3A4 and CYP2C19. Omeprazole is metabolized to two major metabolites, 5-hydroxyomeprazole (CYP2C19) and omeprazole sulfone (CYP3A4). Minor mutations in CYP2C19 affect its activity in the liver and, in turn, the metabolic and pharmacokinetic profiles of omeprazole. The frequency of CYP2C19 poor metabolizers in population of Asian descent has been reported to range from 10 to 20%. Accordingly, results from population studies indicate that omeprazole can be used as a probe drug for phenotyping CYP2C19. The optical isomers of omeprazole show a clear difference in their metabolism by human liver microsomes. This study demonstrates the stereospecific analysis of omeprazole in human plasma as a probe drug of CYP2C19 phenotyping. The chiral separation of omeprazole was achieved on a chiral column with circular dichroism (CD) detection and LC/MS. A good resolution of enantiomers was obtained. The column used for chiral separation was CHIRALPAK AD-RH column (4.6×150 mm) using phosphate buffer and (or ammonium acetate) acetonitrile as an eluent. After a single oral dose of omeprazole (20 mg), the plasma concentrations of the separate enantiomers of omeprazole were determined for 3.5 h after drug intake. The present study is useful because of the part polymorphism plays in the therapeutic effectiveness of proton pump inhibitors during the treatment of acid-related diseases.

KW - Circular dichroism detection

KW - CYP2C19

KW - Cytochrome P-450

KW - LC/MS

KW - Omeprazole

KW - Proton pump inhibitor

KW - Stereospecific analysis

UR - http://www.scopus.com/inward/record.url?scp=0037437688&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037437688&partnerID=8YFLogxK

U2 - 10.1016/S0731-7085(02)00524-1

DO - 10.1016/S0731-7085(02)00524-1

M3 - Article

C2 - 12485723

AN - SCOPUS:0037437688

VL - 30

SP - 1817

EP - 1824

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

IS - 6

ER -