Impact of genetic polymorphisms in CYP2C9 and CYP2C19 on the pharmacokinetics of clinically used drugs

Takeshi Hirota, Shunsuke Eguchi, Ichiro Ieiri

Research output: Contribution to journalReview article

65 Citations (Scopus)

Abstract

Human cytochrome P450 (CYP) is a superfamily of hemoproteins which oxidize a number of endogenous compounds and xenobiotics. The human CYP2C subfamily consists of four members: CYP2C8, CYP2C9, CYP2C18 and CYP2C19. CYP2C9 and CYP2C19 are important drug-metabolizing enzymes and together metabolize approximately 20% of therapeutically used drugs. Forty-two allelic variants for CYP2C9 and 34 for CYP2C19 have been reported. The frequencies of these variants show marked inter-ethnic variation. The functional consequences of genetic polymorphisms have been examined, and many studies have shown the clinical importance of these polymorphisms. Current evidence suggests that taking the genetically determined metabolic capacity of CYP2C9 and CYP2C19 into account has the potential to improve individual risk/benefit relationships. However, more prospective studies with clinical endpoints are needed before the paradigm of "personalized medicine" based on the variants can be established. This review summarizes the currently available important information on this topic.

Original languageEnglish
Pages (from-to)28-37
Number of pages10
JournalDrug metabolism and pharmacokinetics
Volume28
Issue number1
DOIs
Publication statusPublished - 2013

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Genetic Polymorphisms
Pharmacokinetics
Pharmaceutical Preparations
Precision Medicine
Xenobiotics
Cytochrome P-450 Enzyme System
Prospective Studies
Cytochrome P-450 CYP2C9
Cytochrome P-450 CYP2C19
Enzymes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

Cite this

Impact of genetic polymorphisms in CYP2C9 and CYP2C19 on the pharmacokinetics of clinically used drugs. / Hirota, Takeshi; Eguchi, Shunsuke; Ieiri, Ichiro.

In: Drug metabolism and pharmacokinetics, Vol. 28, No. 1, 2013, p. 28-37.

Research output: Contribution to journalReview article

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abstract = "Human cytochrome P450 (CYP) is a superfamily of hemoproteins which oxidize a number of endogenous compounds and xenobiotics. The human CYP2C subfamily consists of four members: CYP2C8, CYP2C9, CYP2C18 and CYP2C19. CYP2C9 and CYP2C19 are important drug-metabolizing enzymes and together metabolize approximately 20{\%} of therapeutically used drugs. Forty-two allelic variants for CYP2C9 and 34 for CYP2C19 have been reported. The frequencies of these variants show marked inter-ethnic variation. The functional consequences of genetic polymorphisms have been examined, and many studies have shown the clinical importance of these polymorphisms. Current evidence suggests that taking the genetically determined metabolic capacity of CYP2C9 and CYP2C19 into account has the potential to improve individual risk/benefit relationships. However, more prospective studies with clinical endpoints are needed before the paradigm of {"}personalized medicine{"} based on the variants can be established. This review summarizes the currently available important information on this topic.",
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N2 - Human cytochrome P450 (CYP) is a superfamily of hemoproteins which oxidize a number of endogenous compounds and xenobiotics. The human CYP2C subfamily consists of four members: CYP2C8, CYP2C9, CYP2C18 and CYP2C19. CYP2C9 and CYP2C19 are important drug-metabolizing enzymes and together metabolize approximately 20% of therapeutically used drugs. Forty-two allelic variants for CYP2C9 and 34 for CYP2C19 have been reported. The frequencies of these variants show marked inter-ethnic variation. The functional consequences of genetic polymorphisms have been examined, and many studies have shown the clinical importance of these polymorphisms. Current evidence suggests that taking the genetically determined metabolic capacity of CYP2C9 and CYP2C19 into account has the potential to improve individual risk/benefit relationships. However, more prospective studies with clinical endpoints are needed before the paradigm of "personalized medicine" based on the variants can be established. This review summarizes the currently available important information on this topic.

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