Clopidogrel decreases the morbidity and mortality associated with several cardiovascular diseases. However, clopidogrel is a prodrug that needs to be metabolized to the active thiol metabolite by the cytochrome P450 (CYP) system. This activation is a source of significant interindividual variability in clopidogrel responsiveness. Drug interactions with and genetic variation in CYP3A4, CYP3A5, a...

BACKGROUND High platelet reactivity (HPR) after clopidogrel treatment is linked to an increased risk of periprocedural myocardial infarction (PMI). The occurrence of PMI that could be associated with CYP2C19 genotype status was our hypothesis. METHODS AND RESULTS A total of 233 patients with non-ST elevation acute coronary syndromes (NSTACS) undergoing uneventful elective percutaneous coronar...

Several in vitro criteria were used to assess whether three methylenedioxyphenyl (MDP) compounds, the isoquinoline alkaloids bulbocapnine, canadine, and protopine, are mechanism-based inactivators of CYP2C19. The recently reported fluorometric CYP2C19 progress curve analysis approach was applied first to determine whether these alkaloids demonstrate time-dependent inhibition. In this experiment...

The evidence for testing for CYP2C19 metabolizer status by CYP2C19 genotyping in patients with need for antiplatelet therapy who are undergoing or being considered for clopidogrel therapy includes 1 randomized controlled trial (RCT) of CYP2C19 genotype-directed antiplatelet therapy, observational studies, and analyses or RCTs of clopidogrel therapy, and meta-analyses of these studies. Relevant ...

BACKGROUND The degree to which cytochrome P450 (CYP) 2C19 genotype influences the effectiveness of clopidogrel remains uncertain because of considerable heterogeneity in results between studies and potential publication bias. Clopidogrel indication and ethnic population have been proposed to influence the effect of CYP2C19 genotype. METHODS AND RESULTS A systematic review was undertaken up to...

AIM To align predicted and measured CYP2C19 phenotype in a South African cohort. MATERIALS & METHODS Genotyping of CYP2C19*2, *3, *9, *15, *17, *27 and *28 was performed using PCR-RFLP, and an activity score (AS) system was used to predict phenotype. True phenotype was measured using plasma concentrations of omeprazole and its metabolite 5'-hydroxyomperazole. RESULTS Partial genotype-phenot...

Voriconazole, a broad-spectrum triazole antifungal agent, is well absorbed, with a high oral bioavailability of 96% (6). Maximal plasma concentrations are observed 1 to 2 h after drug administration. The volume of distribution is estimated to be 4.6 liters/kg, and the plasma protein binding is 58%. A terminal elimination half-life (t1/2) of 8 h in CYP2C19 extensive metabolizers (EMs) and a t1/2...

Objective(s): Alteration in drug metabolism is very likely in diabetes mellitus. This study assessed changes in CYP2C19 enzymatic activity in the liver using omeprazole as a probe in the animal model of type II diabetes (T2DM) before and after treatment with metformin and cinnamon.Materials and Methods: Twenty-eight male Wistar rats were...

Clopidogrel is an antiplatelet prodrug that is recommended to reduce the risk of recurrent thrombosis in coronary artery disease (CAD) patients. Paraoxonase 1 (PON1) is suggested to be a rate-limiting enzyme in the conversion of 2-oxo-clopidogrel to active thiol metabolite with inconsistent results. Here, we sought to determine the associations of CYP2C19 and PON1 gene polymorphisms with clopid...

This work evaluated the kinetic behavior of fluoxetine O-dealkylation in human liver microsomes from different CYP2C19 genotypes and identified the isoenzymes of cytochrome P450 involved in this metabolic pathway. The kinetics of the rho-trifluoromethylphenol (TFMP) formation from fluoxetine was determined in human liver microsomes from three homozygous (wt/wt) and three heterozygous (wt/m1) ex...