How polymorphisms of the cytochrome P450 genes affect ibuprofen and diclofenac metabolism and toxicity / Kako polimorfizmi gena citokroma P450 utječu na metabolizam i toksičnost ibuprofena i diklofenaka

Abstract

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.

Simulated Microgravity Altered the Metabolism of Loureirin B and the Expression of Major Cytochrome P450 in Liver of Rats

“…The results of metabolizing CYP450 tests demonstrated that at least four major CYP450 isoforms were responsible for the metabolism of LB, which was noticeable considering that DB might be co-administered with other drugs also eliminated by CYP450. For example, promethazine, the standard agent for space motion sickness ( Paule et al, 2004 ), is metabolized by CYP2D ( Litzenburger et al, 2015 ); zolpidem, one of the medications for sleep promotion ( Shi et al, 2003 ), is metabolized by CYP3A ( Hesse et al, 2003 ) and ibuprofen, used for pain relief during spaceflight ( Graebe et al, 2004 ), is metabolized by CYP2C ( Krasniqi et al, 2016 ). Hence, the co-administration of DB with other drugs might lead to potential drug–drug interaction and adverse effects, which should be fully predicted.…”

Implications of genetic variation of common Drug Metabolizing Enzymes and ABC Transporters among the Pakistani Population

“…This enzyme metabolizes many drugs, such as warfarin 33 , phenytoin 34 and non-steroidal anti-inflammatory drugs diclofenac and ibuprofen 35 . Our results show an intermediate prevalence of CYP2C9*2 genotype in KHI (6.8%) as compared to Caucasian (10.4%) and African (0%) populations in HapMap database.…”

Efficacy of piroxicam for postoperative pain after lower third molar surgery associated with <em>CYP2C8*3</em> and <em>CYP2C9</em>

“…The vast majority of articles are related to pharmacokinetics, metabolism and adverse reactions of NSAIDs, such as gastrointestinal bleeding,2–6,10,12,13,28 but not the clinical control of inflammatory signs after surgical procedures. Some articles have shown pharmacogenetic impacts on large surgeries, such as the need for prior genetic analysis of patients before bariatric surgeries, regarding the lower use of opioids and lower rates of postoperative pain;29 The study of Murto et al30 shows the impact of CYP2C9*3 on lower postoperative pain rates after adenotonsillectomy surgeries in children taking celecoxib.…”