Tolbutamide is a sulfonylurea-type oral hypoglycemic agent whose action is terminated by hydroxylation of the tolylsulfonyl methyl moiety catalyzed by cytochrome P-450 (CYP) enzymes of the human CYP2C subfamily. Although most studies have implicated CYP2C9 as the exclusive catalyst of hepatic tolbutamide hydroxylation in humans, there is evidence that other CYP2C enzymes (e.g., CYP2C19) may als...

proton-pump inhibitor (PPI) is recommended for patients with a high risk of gastrointestinal bleeding induced by nonsteroidal anti-inflammatory drugs (NSAIDs).1,2 PPIs utilize CYP2C19, a liver enzyme of cytochrome P450, for their inactivation, and this same enzyme mediates the generation of the active substance from the prodrug, clopidogrel, a platelet ADP-receptor blocker.1,2 Therefore, concer...

BACKGROUND Cytochrome P450 (CYP) 2C19 is an enzyme involved in the bioactivation of various important therapeutic drugs, from pro-drugs to an active inhibitor of platelet action. Variants in the CYP2C19 gene influence the pharmacokinetics and clinical response to antiplatelet drugs such as clopidogrel; however, there is no available data about the genetic variation of CYP2C19 in the Hakka popul...

Dual antiplatelet therapy with clopidogrel and aspirin has become the mainstay of therapy for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary interventions (PCI). Many pharmacokinetic and pharmacodynamic studies have demonstrated substantial interindividual variation in antiplatelet response with clopidogrel, a significant proportion of which is explained by the var...

CYP2C19 is an important human drug-metabolizing enzyme that metabolizes a number of clinically used drugs including the antiulcer drug omeprazole, the anxiolytic drug diazepam, the beta-blocker propranolol, the antimalarial drug proguanil, certain antidepressants and barbiturates, and the prototype substrate S-mephenytoin. Previous studies show that compounds such as rifampicin and dexamethason...

background: clopidogrel is one of the most commonly prescribed drugs to prevent ischemic events following coronary syndromes or stent placement. however, impaired responses to therapy as well as resistance are also reported. genetic variants play an important role in clopidogrel biotransformation to its active metabolite that may subsequently influence the clopidogrel antiplatelet effect. the o...

Clopidogrel is an antiplatelet agent widely used in cardiovascular diseases and an inactive prodrug that needs to be converted to an active metabolite in two sequential metabolic steps. Several CYP450 isoforms involved in these two steps have been described, although the relative contribution in vivo of each enzyme is still under debate. CYP2C19 is considered to be the major contributor to acti...

Individuals vary widely in their response to drug treatment. After receiving doses of a drug that are recommended based on a population average, some patients could have an insufficient response, whereas others may experience adverse effects. Of the many factors causing variability in drug response across individuals, genetic polymorphism of drug-metabolizing enzymes is deemed to be one of the ...

We investigated the enzyme kinetic basis for the stereoselective disposition of R- and S-omeprazole (OME) and racemic OME in human liver microsomes. OME is primarily metabolized by the hepatic cytochrome P450 enzyme system (CYP2C19 and 3A4). The metabolism of each enantiomer and pseudoracemic OME was studied using unlabeled and (13)C(7)-labeled enantiomers. The enantiomers inhibited each other'...

PURPOSE Genetic polymorphisms have been linked to an increased predisposition to developing certain diseases. For example, patients of Han-Chinese descent carrying the HLA-B*1502 allele are at an increased risk of developing Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) if given carbamazepine. Given the complexity of in vivo drug metabolism, it is plausible that the activity...