Celecoxib for the Right Person at the Right Dose and Right Time: An Updated Overview
Celecoxib is the only FDA selective cyclooxygenase-2 (COX-2) inhibitor approved nowadays. Studies showed that its therapeutic efficacy and toxicity may be related to inter-individual variability in pharmacodynamics and pharmacokinetics. This review aims to give an updated overview on celecoxib pharmacodynamics and pharmacokinetics in relation to genetics. For this purpose, a Medline search was performed to collect relevant literature between 2004 and 2014. Studies showed that single nucleotide polymorphism (SNP) in PTGS2-765G>C does not control COX-2 inhibitory effect of celecoxib. PGTS1 mutations may have an impact on the selectivity of celecoxib and as such on its gastrointestinal adverse events. Moreover, CYP2C9*2 and *3 allele were identified in bleeding patients taking celecoxib versus control patients. CYP2C9*2, CYP2C*3, two PTGS1 SNPs, and other variant genotypes have shown an association with acute coronary syndromes in patients taking celecoxib. As for the metabolism of celecoxib, in vitro and ex vivo studies showed a reduced clearance of celecoxib in individuals carrier of CYP2C9*3 allele and to a lower extent with CYP2C9*2 carriers. Studies also demonstrated that CYP2C8 does not have a major role in the metabolism of celecoxib. Non-conclusive data are found on the Uridine diphosphate glucuronosyltransferases (UGTs) which catalyze the second phase of the metabolism of celecoxib. As a conclusion, celecoxib should be used with caution in patients known or suspected to be poor CYP2C9 metabolizers. As for CYP2C8, UGTs and other genotypes further studies are still needed to confirm their role in the administration of celecoxib to the right person at the right dose and right time.
Springer Science Reviews ,Volume 3, Issue 2 , pp 137-140