Effects of CYP2C9∗1/∗3 genotype on the pharmacokinetics of flurbiprofen in Korean subjects

Yun Jeong Lee; Ji Yeong Byeon; Young Hoon Kim; Se Hyung Kim; Chang Ik Choi; Jung Woo Bae; Uy Dong Sohn; Choon Gon Jang; Jeongmi Lee; Seok Yong Lee

doi:10.1007/s12272-015-0580-0

Effects of CYP2C9∗1/∗3 genotype on the pharmacokinetics of flurbiprofen in Korean subjects

Yun Jeong Lee, Ji Yeong Byeon, Young Hoon Kim, Se Hyung Kim, Chang Ik Choi, Jung Woo Bae, Uy Dong Sohn, Choon Gon Jang, Jeongmi Lee, Seok Yong Lee

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

The aim of this study was to investigate the impact of CYP2C9∗1/∗3 genotype on the pharmacokinetics of flurbiprofen and its metabolite. The CYP2C9 genotypes were determined with the use of polymerase chain reaction and restriction fragment and DNA sequencing analysis in 358 healthy Koreans. Among them, twenty individuals with CYP2C9∗1/∗1 (n = 12) or CYP2C9∗1/∗3 (n = 8) genotypes received a single 40 mg oral dose of flurbiprofen. The plasma concentrations of flurbiprofen and its metabolite, 4′-hydroxyflurbiprofen were measured by HPLC. AUC_inf of flurbiprofen was significantly higher and its clearance was significantly lower in the CYP2C9∗1/∗3 individuals than in those with CYP2C9∗1/∗1. The AUC ratio of 4'-hydroxyflurbiprofen to flurbiprofen was significantly lower in the CYP2C9∗1/∗3 individuals than in those with CYP2C9∗1/∗1. These results indicate that the individuals carrying of CYP2C9∗3 have significant reduction in flurbiprofen metabolism. The clinical use of this information may allow for more efficient personalized pharmacotherapy.

Original language	English
Pages (from-to)	1232-1237
Number of pages	6
Journal	Archives of Pharmacal Research
Volume	38
Issue number	6
DOIs	https://doi.org/10.1007/s12272-015-0580-0
State	Published - 11 Jun 2015

Keywords

Allele
CYP2C9
Flurbiprofen
Genotype
Polymorphisms

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title = "Effects of CYP2C9∗1/∗3 genotype on the pharmacokinetics of flurbiprofen in Korean subjects",

abstract = "The aim of this study was to investigate the impact of CYP2C9∗1/∗3 genotype on the pharmacokinetics of flurbiprofen and its metabolite. The CYP2C9 genotypes were determined with the use of polymerase chain reaction and restriction fragment and DNA sequencing analysis in 358 healthy Koreans. Among them, twenty individuals with CYP2C9∗1/∗1 (n = 12) or CYP2C9∗1/∗3 (n = 8) genotypes received a single 40 mg oral dose of flurbiprofen. The plasma concentrations of flurbiprofen and its metabolite, 4′-hydroxyflurbiprofen were measured by HPLC. AUCinf of flurbiprofen was significantly higher and its clearance was significantly lower in the CYP2C9∗1/∗3 individuals than in those with CYP2C9∗1/∗1. The AUC ratio of 4'-hydroxyflurbiprofen to flurbiprofen was significantly lower in the CYP2C9∗1/∗3 individuals than in those with CYP2C9∗1/∗1. These results indicate that the individuals carrying of CYP2C9∗3 have significant reduction in flurbiprofen metabolism. The clinical use of this information may allow for more efficient personalized pharmacotherapy.",

keywords = "Allele, CYP2C9, Flurbiprofen, Genotype, Polymorphisms",

author = "Lee, {Yun Jeong} and Byeon, {Ji Yeong} and Kim, {Young Hoon} and Kim, {Se Hyung} and Choi, {Chang Ik} and Bae, {Jung Woo} and Sohn, {Uy Dong} and Jang, {Choon Gon} and Jeongmi Lee and Lee, {Seok Yong}",

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AU - Lee, Yun Jeong

AU - Byeon, Ji Yeong

AU - Kim, Young Hoon

AU - Kim, Se Hyung

AU - Choi, Chang Ik

AU - Bae, Jung Woo

AU - Sohn, Uy Dong

AU - Jang, Choon Gon

AU - Lee, Jeongmi

AU - Lee, Seok Yong

PY - 2015/6/11

Y1 - 2015/6/11

N2 - The aim of this study was to investigate the impact of CYP2C9∗1/∗3 genotype on the pharmacokinetics of flurbiprofen and its metabolite. The CYP2C9 genotypes were determined with the use of polymerase chain reaction and restriction fragment and DNA sequencing analysis in 358 healthy Koreans. Among them, twenty individuals with CYP2C9∗1/∗1 (n = 12) or CYP2C9∗1/∗3 (n = 8) genotypes received a single 40 mg oral dose of flurbiprofen. The plasma concentrations of flurbiprofen and its metabolite, 4′-hydroxyflurbiprofen were measured by HPLC. AUCinf of flurbiprofen was significantly higher and its clearance was significantly lower in the CYP2C9∗1/∗3 individuals than in those with CYP2C9∗1/∗1. The AUC ratio of 4'-hydroxyflurbiprofen to flurbiprofen was significantly lower in the CYP2C9∗1/∗3 individuals than in those with CYP2C9∗1/∗1. These results indicate that the individuals carrying of CYP2C9∗3 have significant reduction in flurbiprofen metabolism. The clinical use of this information may allow for more efficient personalized pharmacotherapy.

AB - The aim of this study was to investigate the impact of CYP2C9∗1/∗3 genotype on the pharmacokinetics of flurbiprofen and its metabolite. The CYP2C9 genotypes were determined with the use of polymerase chain reaction and restriction fragment and DNA sequencing analysis in 358 healthy Koreans. Among them, twenty individuals with CYP2C9∗1/∗1 (n = 12) or CYP2C9∗1/∗3 (n = 8) genotypes received a single 40 mg oral dose of flurbiprofen. The plasma concentrations of flurbiprofen and its metabolite, 4′-hydroxyflurbiprofen were measured by HPLC. AUCinf of flurbiprofen was significantly higher and its clearance was significantly lower in the CYP2C9∗1/∗3 individuals than in those with CYP2C9∗1/∗1. The AUC ratio of 4'-hydroxyflurbiprofen to flurbiprofen was significantly lower in the CYP2C9∗1/∗3 individuals than in those with CYP2C9∗1/∗1. These results indicate that the individuals carrying of CYP2C9∗3 have significant reduction in flurbiprofen metabolism. The clinical use of this information may allow for more efficient personalized pharmacotherapy.

KW - Allele

KW - CYP2C9

KW - Flurbiprofen

KW - Genotype

KW - Polymorphisms

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JO - Archives of Pharmacal Research

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Effects of CYP2C9∗1/∗3 genotype on the pharmacokinetics of flurbiprofen in Korean subjects

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