| Abstrakt: |
Polymorphisms in CYP2C8and CYP2C9are common in all the human populations and many CYP2C8and CYP2C9gene variations cause decreased enzyme activity towards the NSAIDs aceclofenac, celecoxib, diclofenac, ibuprofen, indomethazine, lornoxicam, meloxicam, naproxen, piroxicam, tenoxicam and valdecoxib. This impairment in drug biodisposition alters drug pharmacokinetics, with carriers of detrimental mutations displaying increased values of AUC and decreased drug clearance. Individuals carrying the gene variants CYP2C83(rs11572080; rs10509681), CYP2C92(rs1799853) or CYP2C93(rs1057910) show increased risk of developing acute gastro intestinal bleeding during the use of NSAID that are CYP2C8 or CYP2C9 substrates. However, it is not known whether parent drugs or products of alternative metabolic pathways are responsible for bleeding. We present an overview of the current knowledge of relevant polymorphisms of CYP2C8and CYP2C9genes, their association with NSAID metabolism and pharmacokinetics and a meta-analysis that confirms the clinical significance of these gene variations with regard to gastrointestinal bleeding. |
