Between 20% and 50% of cardiovascular patients treated with clopidogrel, an anti-P2Y12 drug, display high on-treatment platelet reactivity (HTPR) and are not adequately protected from major adverse cardiovascular events (MACE). Despite a minor influence of the CYP2C19*2 genetic variant on the pharmacodynamic response to clopidogrel (5% to 12%) and a limited or absent value for predicting stent ...

BACKGROUND The aim of this study was to analyze the CYP2C19 genetic polymorphism among Han and Uyghur patients with cardiovascular and cerebrovascular diseases in the Kashi area of Xinjiang. MATERIAL/METHODS We enrolled 1020 patients with cardiovascular and cerebrovascular diseases, including 220 Han subjects and 800 Uyghur subjects. We used the gene chip method to detect polymorphisms in CYP...

We examined the distribution of major allelic variants of CYP2C9 and CYP2C19 in the Mongolian population of China and compared it with that of other populations. The polymorphisms of CYP2C9 (including the CYP2C9*1, CYP2C9*2 and CYP2C9*3 alleles) and CYP2C19 (including the CYP2C19*1, CYP2C19*2 and CYP2C19*3 alleles) were analyzed in 280 healthy unrelated Chinese Mongolian subjects, using a PCR-R...

The ability of tricyclic antidepressants (TCAs) to inhibit phenytoin p-hydroxylation was evaluated in vitro by incubation studies of human liver microsomes and cDNA-expressed cytochrome p450s (p450s). The TCAs tested were amitriptyline, imipramine, nortriptyline, and desipramine. Amitriptyline and imipramine strongly and competitively inhibited phenytoin p-hydroxylation in microsomal incubation...

Quantifying variability in pharmacokinetics (PK) and toxicokinetics (TK) provides a science-based approach to refine uncertainty factors (UFs) for chemical risk assessment. In this context, genetic polymorphisms cytochromes P450 (CYPs) drive inter-phenotypic differences may result reduction or increase metabolism of drugs other xenobiotics. Here, an extensive literature search was performed ide...

BACKGROUND Clopidogrel requires oxidation dependent on the cytochrome P450 enzyme 2C19 (CYP2C19) to form its active metabolite. The importance of loss-of-function alleles (particularly CYP2C19*2, 681G>A) in poor platelet response to clopidogrel is well recognized. OBJECTIVE To investigate the prevalence and prognostic impact of the CYP2C19*2 allele in a local acute coronary syndrome (ACS) pop...

It has been previously reported that omeprazole (OP) oxidation is mediated by CYP2C19 and CYP3A4 in human livers. In this study, we assessed their relative contributions with human liver microsomal fractions from Chinese populations that were genotyped by CYP2C19 and recruited from two ethnic groups, Han and Zhuang. The kinetics of 5-hydroxyomeprazole (5-OH-OP) formation was best described by t...

CYP2C19 is an important enzyme for human drug metabolism, and it also participates in the metabolism of endogenous substrates, whereas the CYP2C18 enzyme is not expressed in human liver despite high mRNA expression. Mice transgenic for the human CYP2C18 and CYP2C19 genes were generated. Quantitative mRNA analysis showed CYP2C18 and CYP2C19 transcripts in liver, kidneys, and heart to be expresse...

INTRODUCTION AND OBJECTIVES CYP2C19*2 and CYP2C19*17 alleles appear to contribute to heterogeneous clopidogrel metabolism. The aims of the present study were to assess the phenotype-genotype relationship of CYP2C19*2 and *17 allele carriage and to explore the clinical impact of those polymorphisms at 6-month follow-up of an acute event in an unselected population of non-ST elevation acute coron...

The aim of the current study is to identify the human cytochrome P450 (P450) isoforms involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. In the in vitro experiments using cDNA-expressed human P450 isoforms, clopidogrel was metabolized to 2-oxo-clopidogrel, the immediate precursor of its pharmacologically active metabolite. CYP1A2,...