Related Experiment Video

Updated: Feb 7, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
08:59

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

8.7K

Clopidogrel Pharmacokinetics in Malaysian Population Groups: The Impact of Inter-Ethnic Variability

Zaril H Zakaria1,2, Alan Y Y Fong3,4,5, Raj K S Badhan6,7

  • 1Ministry of Health Malaysia, Block E1, E3, E6, E7 & E10, Parcel E, Federal Government Administration Centre, Putrajaya 62590, Malaysia. zakariz1@aston.ac.uk.

Pharmaceuticals (Basel, Switzerland)
|July 28, 2018
PubMed

Insights

Pharmacogenetic differences in Malaysians affect clopidogrel metabolism, impacting cardiovascular event prevention. A high-dose strategy partially restored therapeutic clopi-H4 levels in poor metabolizers.

Area of Science:

  • Pharmacogenomics
  • Clinical Pharmacology
  • Cardiovascular Medicine

Background:

  • Cardiovascular disease (CVD) is a leading cause of mortality in Malaysia, with clopidogrel used for secondary prevention.
  • Clopidogrel efficacy depends on its active metabolite, clopi-H4, influenced by CYP2C19 enzyme activity.
  • CYP2C19 genetic polymorphisms are prevalent in the Malaysian population, potentially causing therapeutic variability.

Purpose of the Study:

  • To investigate the impact of inter-ethnicity pharmacogenetic variability on clopi-H4 plasma concentrations in Malaysians.
  • To assess the effectiveness of different CYP2C19 genotypes on clopidogrel's therapeutic efficacy.
  • To evaluate pharmacokinetic (PK) modeling for optimizing clopidogrel dosing strategies.

Main Methods:

  • Pharmacokinetic (PK) modeling was employed to analyze clopi-H4 plasma concentrations.
  • Comparison of clopi-H4 Cmax between extensive (EM) and poor metabolizer (PM) phenotypes across Malay and Malaysian Chinese groups.
  • Evaluation of a high-dose clopidogrel strategy (600 mg loading, 150 mg maintenance) in PM individuals.

Main Results:

  • A statistically significant difference (P < 0.001) in clopi-H4 Cmax was observed between EM and PM phenotypes in both ethnic groups.
  • A substantial number of PM individuals had sub-therapeutic peak clopi-H4 concentrations.
  • The high-dose strategy increased the proportion of subjects achieving minimum therapeutic clopi-H4 levels by approximately 50%.

Conclusions:

  • Inter-ethnicity CYP2C19 variability significantly impacts clopidogrel metabolism and therapeutic concentration attainment in Malaysia.
  • A high-dose clopidogrel regimen can partially overcome the reduced efficacy associated with CYP2C19 poor metabolizer status.
  • Personalized dosing strategies based on pharmacogenetics are crucial for optimizing clopidogrel therapy in diverse Malaysian populations.

Keywords:
CVDMalaysianPBPKclopidogrelpharmacokinetics

More Related Videos

High Throughput Analysis of Liquid Droplet Impacts09:00

High Throughput Analysis of Liquid Droplet Impacts

Published on: March 6, 2020

7.0K
How to Calculate and Validate Inter-brain Synchronization in a fNIRS Hyperscanning Study05:33

How to Calculate and Validate Inter-brain Synchronization in a fNIRS Hyperscanning Study

Published on: September 8, 2021

7.5K

Related Concept Videos

Analysis of Population Pharmacokinetic Data01:12

Analysis of Population Pharmacokinetic Data

Analysis of population pharmacokinetic data involves studying the behavior of drugs within diverse populations to understand their pharmacokinetic parameters. Traditional pharmacokinetic methods typically involve collecting samples from a few individuals and estimating these parameters. While these methods are commonly used, they have limitations in capturing the variability in drug response among individuals or heterogeneous populations. Population pharmacokinetics is employed to address these...
758
Ethnic Identity within a Larger Culture01:27

Ethnic Identity within a Larger Culture

Adolescents from ethnic minority backgrounds face a multifaceted journey in forming their identities, shaped by the intersections of cultural expectations and personal exploration. For these adolescents, identity formation involves not only typical developmental challenges but also navigating the perceptions and attitudes of the majority culture. As they grow, adolescents in ethnic minority groups often become increasingly aware of stereotypes, social biases, and discrimination, all of which...
344
Conservation of Small Populations02:04

Conservation of Small Populations

Small population sizes put a species at extreme risk of extinction due to a lack of variation, and a consequent decrease in adaptability. This weakens the chances of survival under pressures such as climate change, competition from other species, or new diseases. Large populations are more likely to survive pressures such as these, as such populations are more likely to harbor individuals that have genetic variants that are adaptive under new stresses. Small populations are much less...
17.4K
What is Population Genetics?01:25

What is Population Genetics?

A population is composed of members of the same species that simultaneously live and interact in the same area. When individuals in a population breed, they pass down their genes to their offspring. Many of these genes are polymorphic, meaning that they occur in multiple variants. Such variations of a gene are referred to as alleles. The collective set of all the alleles within a population is known as the gene pool.
64.8K
Population Growth00:57

Population Growth

Population size is dynamic, increasing with birth rates and immigration, and decreasing with death rates and emigration. In ideal conditions with unlimited resources, populations can increase exponentially, which plots as a J-shaped growth rate curve of population size against time. This type of curve is characteristic of newly-introduced invasive species, or populations that have suffered catastrophic declines and are rebounding.
28.7K
Impact of Groups on Groups01:19

Impact of Groups on Groups

Social psychologists analyze how groups influence one another, shaping social structures and interactions through both cooperation and competition. These dynamics manifest in various ways, ranging from economic partnerships to intergroup conflicts that shape societal structures and perceptions.Cooperation and Competition in Intergroup RelationsIntergroup relationships vary across contexts, sometimes fostering cooperation and mutual benefit while at other times leading to conflict and...
254