Evaluation of the relationship between polymorphisms in CYP2C8 and CYP2C9 and the pharmacokinetics of celecoxib. (17th September 2013)

• Record Type: Journal Article
• Authors: Prieto‐Pérez, Rocío; Ochoa, Dolores; Cabaleiro, Teresa; Román, Manuel; Sánchez‐Rojas, Sergio Daniel; Talegón, María; Abad‐Santos, Francisco
• Is Part Of: Journal of clinical pharmacology. Volume 53:Number 12(2013:Dec.)
• Page Start: 1261
• Page End: 1267
• Publication Date: 2013-09-17
• Subjects: Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1002/jcph.169
• Languages: English
• ISSNs: 0091-2700

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="jcph169-sec-0001" sec-type="section"> <p>Celecoxib is metabolized by enzymes of the cytochrome P450 (CYP450) superfamily, mainly CYP2C9 and CYP3A4. Polymorphisms in the <italic>CYP2C9</italic> gene have been associated with decreased enzyme activity and alteration of celecoxib pharmacokinetic parameters. However, literature reports are limited, and some results are contradictory. We enrolled 24 healthy volunteers in a single‐dose replicated crossover trial with celecoxib 200 mg. We evaluated the association between single‐nucleotide polymorphisms in the <italic>CYP2C8</italic> and <italic>CYP2C9</italic> genes (CYP2C8*2, CYP2C8*3, CYP2C8*4, CYP2C9*2, and CYP2C9*3) of these individuals and the pharmacokinetic parameters of celecoxib. Subjects carrying CYP2C9*1/*3 and CYP2C9*3/*3 had a higher AUC (2‐ and 7.7‐fold, respectively) and C_max (1.5‐ and 1.8‐fold, respectively) and lower clearance (2.3‐ and 10‐fold, respectively) than those carrying CYP2C9*1/*1. Half‐life was 2.7‐fold higher in subjects with CYP2C9*3/*3 than in those with the wild type but not in those with CYP2C9*1/*3. We did not find any significant effect of gender or <italic>CYP2C8</italic> polymorphisms on the pharmacokinetics of celecoxib. In conclusion, the recommended dose of celecoxib should be decreased in CYP2C9*3 carriers, especially in homozygous subjects.</p> </sec> </abstract>