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Review article

How polymorphisms of the cytochrome P450 genes affect ibuprofen and diclofenac metabolism and toxicity

Valon Krasniqi ; University of Prishtina Faculty of Medicine, Prishtina, Kosovo
Aleksandar Dimovski ; Ss. Cyril and Methodius University of Skopje Faculty of Pharmacy, Skopje, Macedonia
Iva Klarica Domjanović ; Agency for Medicinal Products and Medical Devices of Croatia
Ivan Bilić ; University of Zagreb School of Medicine, Zagreb, Croatia
Nada Božina ; University Hospital Centre Zagreb, Zagreb, Croatia

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Interindividual variability in drug metabolism is an important cause of adverse drug reactions and variability in drug efficiency. Polymorphisms of cytochrome P450 (CYPs) genes have a significant effect on drug metabolism and toxicity. This review brings an update about how genetic polymorphisms of CYP2C8 and CYP2C9 enzymes affect the disposition and clinical outcomes of ibuprofen and diclofenac, two of the most common pain relievers. The most common side effects associated with the influence of CYP2C8*3 and CYP2C9*2*3 variants on ibuprofen and diclofenac pharmacokinetics are hepatotoxicity and gastrointestinal bleeding. CYP genotyping may therefore identify patients at increased risk of these adverse reactions, and these patients could have their doses adjusted or start receiving another NSAID that does not share the same metabolic pathways with ibuprofen or diclofenac. However, before genotyping is introduced into regular clinical practice, more research is needed to evaluate the effectiveness of this strategy in improving treatment with ibuprofen and diclofenac.


adverse effects; allelic variants; CYP2C8; CYP2C9; drug metabolism; gastrointestinal bleeding; genotyping; hepatotoxicity; pharmacogenetics; pharmacogenomics; pharmacokinetics

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