BACKGROUND The phenomenon of CYP2C19 polymorphism affects the metabolism of both clopidogrel and proton-pump inhibitors (PPI). However, concomitant use of both drugs may reduce the desired therapeutic effects. In this study, we evaluated whether individuals with different numbers of reduced-function CYP2C19 alleles were equally affected and whether PPIs with different dependencies on CYP2C19 me...

OBJECTIVES Voriconazole exhibits highly variable, non-linear pharmacokinetics and is associated with a narrow therapeutic range. This study aimed to investigate the population pharmacokinetics of voriconazole in adults, including the effect of CYP2C19 genotype and drug-drug interactions. METHODS Non-linear mixed effects modelling (NONMEM) was undertaken of six voriconazole studies in healthy ...

Human cytochrome P450 (CYP) is a superfamily of hemoproteins which oxidize a number of endogenous compounds and xenobiotics. The human CYP2C subfamily consists of four members: CYP2C8, CYP2C9, CYP2C18 and CYP2C19. CYP2C9 and CYP2C19 are important drug-metabolizing enzymes and together metabolize approximately 20% of therapeutically used drugs. Forty-two allelic variants for CYP2C9 and 34 for CY...

Cytochrome P450 enzymes from the CYP2C subfamily play a prominent role in the metabolic clearance of many drugs. CYP2C enzymes have also been implicated in the metabolism of arachidonic acid to vasoactive epoxyeicosatrienoic acids. CYP2C8, CYP2C9, and CYP2C19 are expressed in the adult liver at significant levels; however, the expression of CYP2C enzymes in extrahepatic tissues such as the brai...

Four large trials, reported in the last several weeks, have identified loss-of-function alleles in the gene encoding cytochrome P450 2C19 (CYP2C19) as important risk factors predicting apparent failure of clopidogrel efficacy.1–4 Previous studies have shown that clopidogrel is a prodrug that requires bioactivation,5 mediated in part by CYP2C19, to achieve its antiplatelet efficacy.6 All 4 trial...

BACKGROUND Dual antiplatelet therapy is the cornerstone in the management of acute coronary syndromes (ACS) and prevention of stent thrombosis (ST). Genetic polymorphisms in CYP2C19 gene involved in hepatic activation of clopidogrel leads to clopidogrel non-responsiveness and may influence clinical outcomes. These polymorphisms in CYP2C19 gene and their impact on clinical outcome in coronary ar...

Cytochrome P450 (CYP) 3A enzymes are responsible for the metabolism of many drugs. It is useful to know CYP3A activity in individual patients undergoing drug therapy so as to predict the efficacies or adverse events. Lansoprazole is metabolized to Lansoprazole sulfone (LS) by CYP3A, while to 5-hydroxylansoprasole by CYP2C19. The aim of this study was to evaluate whether lansoprazole can be used...

Objective. Potential interactions between herbal extracts and the cytochrome P450 (CYP) system lead to serious adverse events or decreased drug efficacy. Rhus verniciflua stoke (RVS) and its constituents have been reported to have various pharmacological properties. We evaluated the inhibitory potential of RVS and its constituents on the major CYP isoforms. Methods. The effects of allergen remo...

BACKGROUND Omeprazole is metabolized by the hepatic cytochrome P450 (CYP) 2C19 enzyme to 5-hydroxyomeprazole. CYP2C19 exhibits genetic polymorphisms responsible for the presence of poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers (EMs). The defective mutations of the enzyme and their frequencies change between different ethnic groups; however, the polymorphism...

The human cytochrome P450 (CYP) is a superfamily of enzymes that have been a focus in research for decades due to their prominent role in drug metabolism. CYP2C is one of the major subfamilies which metabolize more than 10% of all clinically used drugs. In the context of CYP2C19, several key genetic variations that alter the enzyme's activity have been identified and catalogued in the CYP allel...