Genetic polymorphisms of CYP2C19*2 and ABCB1 C3435T affect the pharmacokinetic and pharmacodynamic responses to clopidogrel in 401 patients with acute coronary syndrome

P-Glycoprotein Polymorphism C3435T Is Associated with Dose-Adjusted Clopidogrel and 2-Oxo-Clopidogrel Concentration

“…A number of previous studies showed no association with platelet response [19,[26][27][28] . Wang et al [22] , on the contrary, have found the relation between this SNP and platelet response, but in the Chinese population with different ABCB1 C3435T genotype distribution. Nevertheless, TT genotype was associated with almost 2-fold higher risk of cardiovascular events (death, AMI, stroke) after PCI [25] , but not the risk of stent thrombosis [25,26] .…”

“…We have shown that patients carrying ABCB1 polymorphic T alleles on position 3,435, had lower clopidogrel concentration. Variant allele homozygotes are associated with lower levels of clopidogrel and active metabolite after loading doses of 300 or 600 mg [9,22,23] . Due to downregulation, when 900 mg loading doses are administered, it was found that the concentration increases [16,23] .…”

Paraoxonase-1 Deficiency does not Influence Clopidogrel Antiplatelet Function in Mice

“…To ensure that genetically modified mice were really PON1-deficient, we measured PON1 lactonase activity in excised liver homogenates, since the liver is a key organ for clopidogrel activation as well as PON1 synthesis [1,16]. For this purpose 30 mg of liver were homogenized in 500 µl of a 25 mM Tris-HCl buffer (pH = 7.4) containing 100 mM NaCl, and 1% Nonidet-40, and using a Precellys 24 homogenizer (Bertin Technologies, France).…”

“…Clopidogrel is an oral, thienopyridide-class, antiplatelet agent used in the treatment of vascular diseases, including peripheral vascular disease [1]. This compound is a pro-drug that requires enzymatic biotransformation into the active thiol metabolite to facilitate its action of inhibiting platelet adenosine diphosphate (ADP) P2Y12 receptor [2] .Early studies described in vivo bio activation of clopidogrel as a two-step process closely linked to the cytochrome P450 (CYP) 2C19 enzyme [3].…”

Genotype Frequencies of CYP2C19, P2Y₁₂ and GPIIIa Polymorphisms in Coronary Heart Disease Patients of Han Ethnicity, and Their Impact on Clopidogrel Responsiveness

“…Genetic variants associated with CYP2C19, P2Y 12 receptor, and GPIIa are associated with reduced formation of the clopidogrel active metabolite, reduced pharmacodynamic response, and reduced platelet function. [10][11][12][13][14] A thorough assessment of the impact of these genetic variants on coronary heart disease and MACE in all major ethnic populations, including those within China, is likely to provide important insights into the risks and possible Vol 57 No 5 POLYMORPHISMS IN CORONARY HEART DISEASE PATIENTS benefits of platelet-directed pharmacotherapy in relation with specific genotypes.…”