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All proton pump inhibitors except for rabeprazole and pantoprazole are metabolized by the hepatic CYP450 enzyme and therefore, may interact with the metabolism of clopidogrel. Omeprazole is considered to have higher potential for drug-drug interaction than other protein pump inhibitors because it is a CYP2C19 inhibitor. [17]
Clopidogrel, sold under the brand name Plavix among others, is an antiplatelet medication used to reduce the risk of heart disease and stroke in those at high risk. [10] It is also used together with aspirin in heart attacks and following the placement of a coronary artery stent (dual antiplatelet therapy). [10]
[55] [56] PPIs are commonly used in people with cardiovascular disease for gastric protection when aspirin is given for its antiplatelet actions. [55] [57] An interaction between PPIs and the metabolism of the platelet inhibitor clopidogrel is known and this drug is also often used in people with cardiac disease.
[3] [4] CYP2C19 is a liver enzyme that acts on at least 10% of drugs in current clinical use, [5] most notably the antiplatelet treatment clopidogrel (Plavix), drugs that treat pain associated with ulcers, such as omeprazole, antiseizure drugs such as mephenytoin, the antimalarial proguanil, and the anxiolytic diazepam. [6]
Due to drug-drug interactions, patients taking clopidogrel, an antiplatelet drug, should not take PPI except rabeprazole. [72] Since PPI changes the acidity of the gastric content, patients taking ketoconazole , atazanavir , iron, erlotinib , and MMF should not take PPI at the same time.
Clopidogrel has a common drug interaction with CYP2C19 inhibitors, particularly omeprazole and esomeprazole which are indicated for treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD). As the activation of clopidogrel requires an enzyme called CYP2C19, its inhibitors should be avoided. [38]
In molecular biology, an interactome is the whole set of molecular interactions in a particular cell.The term specifically refers to physical interactions among molecules (such as those among proteins, also known as protein–protein interactions, PPIs; or between small molecules and proteins [1]) but can also describe sets of indirect interactions among genes (genetic interactions).
Targeted covalent inhibitors (TCIs) or Targeted covalent drugs are rationally designed inhibitors that bind and then bond to their target proteins.These inhibitors possess a bond-forming functional group of low chemical reactivity that, following binding to the target protein, is positioned to react rapidly with a proximate nucleophilic residue at the target site to form a bond.