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

Zaril Zakaria, Alan Fong, Raj Badhan

Research output: Contribution to journalArticle

Abstract

Malaysia is a multi-ethnic society whereby the impact of pharmacogenetic differences between ethnic groups may contribute significantly to variability in clinical therapy. One of the leading causes of mortality in Malaysia is cardiovascular disease (CVD), which accounts for up to 26% of all hospital deaths annually. Clopidogrel is used as an adjunct treatment in the secondary prevention of cardiovascular events. CYP2C19 plays an integral part in the metabolism of clopidogrel to the active metabolite clopi-H4. However, CYP2C19 genetic polymorphism, prominent in Malaysians, could influence target clopi-H4 plasma concentrations for clinical efficacy. This study addresses how inter-ethnicity variability within the Malaysian population impacts the attainment of clopi-H4 target plasma concentration under different CYP2C19 polymorphisms through pharmacokinetic (PK) modelling. We illustrated a statistically significant difference (P < 0.001) in the clopi-H4 Cmax between the extensive metabolisers (EM) and poor metabolisers (PM) phenotypes with either Malay or Malaysian Chinese population groups. Furthermore, the number of PM individuals with peak clopi-H4 concentrations below the minimum therapeutic level was partially recovered using a high-dose strategy (600 mg loading dose followed by a 150 mg maintenance dose), which resulted in an approximate 50% increase in subjects attaining the minimum clopi-H4 plasma concentration for a therapeutic effect.
Original languageEnglish
Article number74
JournalPharmaceuticals
Volume11
Issue number3
DOIs
Publication statusPublished - 26 Jul 2018

Fingerprint

clopidogrel
Population Groups
Pharmacokinetics
Malaysia
Pharmacogenetics
Therapeutic Uses
Genetic Polymorphisms
Secondary Prevention
Ethnic Groups
Cardiovascular Diseases
Therapeutics
Phenotype
Mortality
Population
Cytochrome P-450 CYP2C19

Bibliographical note

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Keywords

  • PBPK
  • pharmacokinetics
  • clopidogrel
  • CVD
  • Malaysian

Cite this

Zakaria, Zaril ; Fong, Alan ; Badhan, Raj. / Clopidogrel Pharmacokinetics in Malaysian Population Groups : The Impact of Inter-Ethnic Variability. In: Pharmaceuticals. 2018 ; Vol. 11, No. 3.
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Clopidogrel Pharmacokinetics in Malaysian Population Groups : The Impact of Inter-Ethnic Variability. / Zakaria, Zaril; Fong, Alan; Badhan, Raj.

In: Pharmaceuticals, Vol. 11, No. 3, 74, 26.07.2018.

Research output: Contribution to journalArticle

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