Effect of CYP2C9*3 mutant variants on meloxicam pharmacokinetics in a healthy Chinese population

Zhang, M.; Yongge, Yang; Zhao, Gang-Tao; Di, Xiaohui; Lin, Xu; Jiang, Nianxin; Xu, Jie; Xu, Xiangmin

doi:10.4238/2014.february.13.1

Cited by 4 publications

(2 citation statements)

References 14 publications

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“…For example, according to the recently reported clinical pharmacogenetics implementation consortium (CPIC) guidelines for non-steroidal anti-inflammatory drugs (NSAIDs) based on CYP2C9 genetic polymorphisms, meloxicam recommends dose adjustment in clinical practice considering CYP2C9 genotypes. 8 This was a review result based on several past reports [9][10][11] that showed large differences in total plasma exposure results after administration of meloxicam depending on CYP2C9 genetic polymorphisms.…”

Section: Introductionmentioning

confidence: 99%

Dosage exploration of meloxicam according to CYP2C9 genetic polymorphisms based on a population pharmacokinetic‐pharmacodynamic model

2023

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Background Meloxicam, used for treating inflammatory diseases, shows large differences in metabolism according to CYP2C9 genetic polymorphisms; however, there are few studies on dose regimen setting based on quantitative predictions. Objective The aim of this study was to determine the appropriate meloxicam dose regimen for each genotype through population pharmacokinetic‐pharmacodynamic modeling of meloxicam by considering CYP2C9 genetic polymorphisms. Methods For modeling, previously reported pharmacokinetic (plasma concentration)‐pharmacodynamic (inhibition of thromboxane B2 generation) data of meloxicam were collected for CYP2C9 genetic polymorphisms (n = 43). And these data were mainly used in the modeling process. Through simulations of the established models, steady‐state pharmacokinetic‐pharmacodynamic profiles were obtained according to meloxicam multiple exposures for each CYP2C9 genotype, and predictions were made based on dose regimen changes. Results Genetic polymorphisms of CYP2C9 were identified as key covariates that significantly affected pharmacokinetic variability of meloxicam between individuals. The developed meloxicam population pharmacokinetic‐pharmacodynamic model predicted pharmacokinetic results of the 7.5 mg meloxicam administration groups (n = 26) for CYP2C9*1/*1 and *1/*3 as an external validation. The results of model simulation revealed that the differences were 2.39–5.42 times for steady‐state mean plasma concentrations and 1.21–1.71 times for the degree of inhibition of thromboxane B2 generation following multiple exposures for CYP2C9*1/*1 versus *1/*13, *1/*3, and *3/*3. This suggested that thromboxane B2 inhibition following increased plasma exposure to meloxicam differed significantly according to CYP2C9 genetic polymorphisms. The dose of meloxicam in CYP2C9*1/*13, *1/*3, and *3/*3 was randomly adjusted to 1.6–15 mg to approximate the mean thromboxane B2 inhibition for CYP2C9*1/*1 at steady state, the dose intervals varied from 24 h to 48 h. Conclusions The results suggested that clinical dose adjustment of meloxicam would be necessary to account for CYP2C9 genetic polymorphisms and reduce side effects. This study suggests a clearer direction for setting up clinical therapy based on personalized medicine and quantitative predictions for meloxicam.

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Section: Introductionmentioning

confidence: 99%

Dosage exploration of meloxicam according to CYP2C9 genetic polymorphisms based on a population pharmacokinetic‐pharmacodynamic model

2023

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“…16,17 However, few studies have been performed in Chinese HVs. 18,19 This study, with fasting and fed arms, was performed to investigate the BE of meloxicam from 2 manufacturers. This was a single-site, single-dose, randomized, open-label, 2-period, 2-sequence, crossover to study the PK and BE of single oral doses of meloxicam tablets in healthy Chinese adults under fasting and fed conditions.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Meloxicam Tablets in Healthy Chinese Adults in the Fasting and Fed States: A Single‐Site, Single‐Dose, Randomized, Open, 2‐Period, 2‐Sequence, Crossover Bioequivalence Study

Yü

Wang

et al. 2021

Clinical Pharm in Drug Dev

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Meloxicam is an enolate nonsteroidal anti-inflammatory agent. This trial investigated the pharmacokinetics, safety, and bioequivalence of single oral doses of Aomei meloxicam (15 mg) and Mobic meloxicam (15 mg) in healthy volunteers under fasting and fed conditions. A single-site, single-dose, randomized, open, 2-period, 2-sequence, crossover bioequivalence study was performed: 24 healthy volunteers were enrolled in each of the fasting and fed arms. Each HV was randomly assigned to receive the Aomei drug (test) in one period and the Mobic drug (reference) in the other period. The concentration of meloxicam in plasma was detected using liquid chromatography-tandem mass spectrometry. The primary pharmacokinetic parameters were calculated using a noncompartmental model. In the fasting arm, the 90% confidence interval of the geometric mean ratios of maximum plasma concentration, area under the concentration-time curve from time 0 to the last measurable plasma concentration, and area under the concentration-time curve from time 0 to infinity between the test and reference products were 99.5% to 111.7%, 101.2% to 106.8%, and 101.8% to 108.3%, respectively. In the fed arm, the 3 parameters were 94.1% to 102.4%, 97.6% to 103.0%, and 97.5% to 103.7%, respectively. These parameters were in the range of 80% to 125%, and the 2 products were considered bioequivalent in both the fasting and fed states and were well tolerated. The severity of all adverse events was mild. Aomei meloxicam tablets and Mobic meloxicam tablets were bioequivalent in healthy Chinese volunteers.

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Physiologically based pharmacokinetic (PBPK) modeling of meloxicam in different CYP2C9 genotypes

et al. 2021

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Effect of CYP2C9*3 mutant variants on meloxicam pharmacokinetics in a healthy Chinese population

Cited by 4 publications

References 14 publications

Dosage exploration of meloxicam according to CYP2C9 genetic polymorphisms based on a population pharmacokinetic‐pharmacodynamic model

Dosage exploration of meloxicam according to CYP2C9 genetic polymorphisms based on a population pharmacokinetic‐pharmacodynamic model

Pharmacokinetics of Meloxicam Tablets in Healthy Chinese Adults in the Fasting and Fed States: A Single‐Site, Single‐Dose, Randomized, Open, 2‐Period, 2‐Sequence, Crossover Bioequivalence Study

Physiologically based pharmacokinetic (PBPK) modeling of meloxicam in different CYP2C9 genotypes

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