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

Zakaria, Zaril, Fong, Alan and Badhan, Raj (2018). Clopidogrel Pharmacokinetics in Malaysian Population Groups:The Impact of Inter-Ethnic Variability. Pharmaceuticals, 11 (3),

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.

Publication DOI: https://doi.org/10.3390/ph11030074
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences > Applied Health Research Group
Life & Health Sciences
Life & Health Sciences > Chronic and Communicable Conditions
Additional Information: © 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/).
Uncontrolled Keywords: PBPK,pharmacokinetics,clopidogrel,CVD,Malaysian
Full Text Link:
Related URLs: http://www.mdpi ... 24-8247/11/3/74 (Publisher URL)
Published Date: 2018-07-26
Authors: Zakaria, Zaril
Fong, Alan
Badhan, Raj ( 0000-0002-0904-9324)

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