Pharmacokinetics and Pharmacodynamics of Meloxicam in East Asian Populations: The Role of Ethnicity on Drug Response

Abstract

We aimed to reanalyze the differences in the pharmacokinetics (PKs) of meloxicam in East Asian populations based on a population approach using previously published data and to investigate the factors found in population PK analysis that affect the pharmacodynamics (PDs) of meloxicam. Population PK analysis was performed in 119 healthy male subjects (30 Japanese, 30 Chinese, 29 Korean, and 30 white) under strictly controlled trial conditions with regulated meals and a single lot of the drug. We found that CYP2C9 genotype and lean body mass were statistically significant predictors of clearance and volume of distribution, respectively. A statistical significant difference in the PK parameters between ethnic groups could not be identified. Simulations using PK/PD models showed that CYP2C9 genotype is the factor that affects the PDs of meloxicam. The genetic polymorphisms highlighted in this study would be beneficial for conducting clinical trials in East Asians with similar genetic backgrounds.

Bioequivalence Study Comparing Meloxicam 15mg Tablet of Pascual Laboratories, Inc. with Meloxicam (Mobic®) 15mg Tablet of Boehringer Ingelheim in Healthy Male Filipino Subjects under Fasting Conditions

“…Other polymorphisms seen in the East Asian subjects showed 15% to 55% decrease in clearance. 16 In a Korean study, a nine-fold lower apparent oral clearance and an eight-fold higher AUC of single-dose meloxicam were observed in CYP2C9*3/*3 individuals. 17 A study among Korean subjects showed that the C max of meloxicam in subjects with CYP2C9*1/*13 was 1.46 times greater compared to subjects with the CYP2C9*1/*1 genotype.…”

The positive and negative effects of using transdermal nonsteroidal anti-inflammatory drugs: chemoreactome analysis

“…Цитохромы системы Р450 осуществляют окисление/гидроксилирование стероидов, жирных кислот, ксенобиотиков и необходимы для трансформаций многочисленных лекарственных средств в организме. Например, известно, что мелоксикам метаболизируется цитохромами CYP2C9 и CYP3A4 [16], причем генотипы *1/*13 цитохрома CYP2C9 влияют на фармакодинамику мелоксикама [17].…”

Modeling of the Weight Status and Risk of Nonalcoholic Fatty Liver Disease in Elderly Individuals: The Potential Impact of the Disulfide Bond‐Forming Oxidoreductase A‐Like Protein (DsbA‐L) Polymorphism on the Weight Status

“…[22][23][24][25] A nonlinear mixed-effect model (NONMEM) is a pharmacometric procedure that is widely applied in pharmacokinetic (PK) and PK/pharmacodynamic (PD) analyses based on longitudinal data, which enables the examination of various base models and the effects of various cofactors, the utilization of all observation points, and the evaluation of validity based on simulation. [22][23][24][25] On the other hand, disease progression models are often integrated with PK/PD models using a NONMEM approach to quantify the influence of various factors on disease progression because of the ability to quantify several levels of variability, to address instability data, and to identify individual specific cofactors. 22,23 Thus, a NONMEM approach can be an effective tool for developing a disease prediction model using clinical information and to help clarify the precise effects of various factors on disease development and progression.…”

“…Pharmacometrics is a relatively recently established science that provides quantitative models regarding the pharmacology through the mathematical modeling of clinical efficacy based on multivariable analyses . A nonlinear mixed‐effect model (NONMEM) is a pharmacometric procedure that is widely applied in pharmacokinetic (PK) and PK/pharmacodynamic (PD) analyses based on longitudinal data, which enables the examination of various base models and the effects of various cofactors, the utilization of all observation points, and the evaluation of validity based on simulation .…”

“…Pharmacometrics is a relatively recently established science that provides quantitative models regarding the pharmacology through the mathematical modeling of clinical efficacy based on multivariable analyses . A nonlinear mixed‐effect model (NONMEM) is a pharmacometric procedure that is widely applied in pharmacokinetic (PK) and PK/pharmacodynamic (PD) analyses based on longitudinal data, which enables the examination of various base models and the effects of various cofactors, the utilization of all observation points, and the evaluation of validity based on simulation . On the other hand, disease progression models are often integrated with PK/PD models using a NONMEM approach to quantify the influence of various factors on disease progression because of the ability to quantify several levels of variability, to address instability data, and to identify individual specific cofactors .…”