Strongly increased exposure of meloxicam in CYP2C9*3/*3 individuals

Hye In Lee; Jung Woo Bae; Chang Ik Choi; Yun Jeong Lee; Ji Yeong Byeon; Choon Gon Jang; Seok Yong Lee

doi:10.1097/FPC.0000000000000025

Strongly increased exposure of meloxicam in CYP2C93/3 individuals

Hye In Lee, Jung Woo Bae, Chang Ik Choi, Yun Jeong Lee, Ji Yeong Byeon, Choon Gon Jang, Seok Yong Lee

Department of Pharmacy

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

28 Scopus citations

Abstract

OBJECTIVE: The effects of CYP2C9*1/*3 and *3/*3 genotypes on the pharmacokinetics and pharmacodynamics of meloxicam were evaluated in healthy Korean subjects. METHODS: After oral administration of 15 mg meloxicam, the plasma concentrations of meloxicam were assessed in 11 CYP2C9*1/*1 individuals, eight CYP2C9*1/*3 individuals, and three CYP2C9*3/*3 individuals. The pharmacodynamic effects were determined by measuring thromboxane B2 generated in blood. RESULTS: A nine-fold lower apparent oral clearance and an eight-fold higher AUC0-∞ of single-dose meloxicam were observed in CYP2C9*3/*3 individuals when compared with CYP2C9*1/*1 individuals. CYP2C9*3/*3 individuals also showed markedly increased inhibition of thromboxane B2 generation by meloxicam. CONCLUSION: These results indicate that CYP2C9*3/*3 individuals may be at a higher risk for concentration-dependent adverse effects during long-term treatment with standard doses of meloxicam.

Original language	English
Pages (from-to)	113-117
Number of pages	5
Journal	Pharmacogenetics and Genomics
Volume	24
Issue number	2
DOIs	https://doi.org/10.1097/FPC.0000000000000025
State	Published - Feb 2014

Keywords

CYP2C9*3
meloxicam
pharmacodynamics
pharmacokinetics

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10.1097/FPC.0000000000000025

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title = "Strongly increased exposure of meloxicam in CYP2C9*3/*3 individuals",

abstract = "OBJECTIVE: The effects of CYP2C9*1/*3 and *3/*3 genotypes on the pharmacokinetics and pharmacodynamics of meloxicam were evaluated in healthy Korean subjects. METHODS: After oral administration of 15 mg meloxicam, the plasma concentrations of meloxicam were assessed in 11 CYP2C9*1/*1 individuals, eight CYP2C9*1/*3 individuals, and three CYP2C9*3/*3 individuals. The pharmacodynamic effects were determined by measuring thromboxane B2 generated in blood. RESULTS: A nine-fold lower apparent oral clearance and an eight-fold higher AUC0-∞ of single-dose meloxicam were observed in CYP2C9*3/*3 individuals when compared with CYP2C9*1/*1 individuals. CYP2C9*3/*3 individuals also showed markedly increased inhibition of thromboxane B2 generation by meloxicam. CONCLUSION: These results indicate that CYP2C9*3/*3 individuals may be at a higher risk for concentration-dependent adverse effects during long-term treatment with standard doses of meloxicam.",

keywords = "CYP2C9*3, meloxicam, pharmacodynamics, pharmacokinetics",

author = "Lee, {Hye In} and Bae, {Jung Woo} and Choi, {Chang Ik} and Lee, {Yun Jeong} and Byeon, {Ji Yeong} and Jang, {Choon Gon} and Lee, {Seok Yong}",

year = "2014",

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doi = "10.1097/FPC.0000000000000025",

language = "English",

volume = "24",

pages = "113--117",

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T1 - Strongly increased exposure of meloxicam in CYP2C9*3/*3 individuals

AU - Lee, Hye In

AU - Bae, Jung Woo

AU - Choi, Chang Ik

AU - Lee, Yun Jeong

AU - Byeon, Ji Yeong

AU - Jang, Choon Gon

AU - Lee, Seok Yong

PY - 2014/2

Y1 - 2014/2

N2 - OBJECTIVE: The effects of CYP2C9*1/*3 and *3/*3 genotypes on the pharmacokinetics and pharmacodynamics of meloxicam were evaluated in healthy Korean subjects. METHODS: After oral administration of 15 mg meloxicam, the plasma concentrations of meloxicam were assessed in 11 CYP2C9*1/*1 individuals, eight CYP2C9*1/*3 individuals, and three CYP2C9*3/*3 individuals. The pharmacodynamic effects were determined by measuring thromboxane B2 generated in blood. RESULTS: A nine-fold lower apparent oral clearance and an eight-fold higher AUC0-∞ of single-dose meloxicam were observed in CYP2C9*3/*3 individuals when compared with CYP2C9*1/*1 individuals. CYP2C9*3/*3 individuals also showed markedly increased inhibition of thromboxane B2 generation by meloxicam. CONCLUSION: These results indicate that CYP2C9*3/*3 individuals may be at a higher risk for concentration-dependent adverse effects during long-term treatment with standard doses of meloxicam.

AB - OBJECTIVE: The effects of CYP2C9*1/*3 and *3/*3 genotypes on the pharmacokinetics and pharmacodynamics of meloxicam were evaluated in healthy Korean subjects. METHODS: After oral administration of 15 mg meloxicam, the plasma concentrations of meloxicam were assessed in 11 CYP2C9*1/*1 individuals, eight CYP2C9*1/*3 individuals, and three CYP2C9*3/*3 individuals. The pharmacodynamic effects were determined by measuring thromboxane B2 generated in blood. RESULTS: A nine-fold lower apparent oral clearance and an eight-fold higher AUC0-∞ of single-dose meloxicam were observed in CYP2C9*3/*3 individuals when compared with CYP2C9*1/*1 individuals. CYP2C9*3/*3 individuals also showed markedly increased inhibition of thromboxane B2 generation by meloxicam. CONCLUSION: These results indicate that CYP2C9*3/*3 individuals may be at a higher risk for concentration-dependent adverse effects during long-term treatment with standard doses of meloxicam.

KW - CYP2C93

KW - meloxicam

KW - pharmacodynamics

KW - pharmacokinetics

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EP - 117

JO - Pharmacogenetics and Genomics

JF - Pharmacogenetics and Genomics

IS - 2

ER -

Strongly increased exposure of meloxicam in CYP2C93/3 individuals

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