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

Ministry of Health Malaysia, Block E1, E3, E6, E7 & E10, Parcel E, Federal Government Administration Centre, Putrajaya 62590, Malaysia
Applied Health Research Group, School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK
Sarawak Heart Centre, Kota Samarahan 94300, Malaysia
Clinical Research Centre, Sarawak General Hospital, Kuching 93586, Malaysia
Aston Pharmacy School, Aston University, Birmingham B4 7ET, UK
Author to whom correspondence should be addressed.
Pharmaceuticals 2018, 11(3), 74;
Received: 31 May 2018 / Revised: 6 July 2018 / Accepted: 8 July 2018 / Published: 26 July 2018
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. View Full-Text
Keywords: PBPK; pharmacokinetics; clopidogrel; CVD; Malaysian PBPK; pharmacokinetics; clopidogrel; CVD; Malaysian
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Zakaria, Z.H.; Fong, A.Y.Y.; Badhan, R.K.S. Clopidogrel Pharmacokinetics in Malaysian Population Groups: The Impact of Inter-Ethnic Variability. Pharmaceuticals 2018, 11, 74.

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