Celecoxib pharmacokinetics in pediatric cancer patients–The effects of food and pharmacogenetics

Abstract

Purpose To determine the single dose and steady state (SS) pharmacokinetics (PK) of the selective COX-2 inhibitor celecoxib in pediatric cancer patients (with & without food) and to correlate PK and CYP2C9 genotype. Methods Celecoxib (250mg/m2) was administered to the patients and PK were assessed after one dose and at SS. Results Single dose and SS PK with and without food are summarized below (age for all=11.5±4.3). In addition, preliminary CYP2C9 genotypic data is available for 4 patients. 2 were CYP2C9*1*1(wildtype) consistent with the extensive metabolizer phenotype, 1 was CYP2C9*1*2 (intermediate metabolizer) and 1 was CYP2C9*3*3 (poor metabolizer). These data correlate well with observed PK parameters. (See table) Conclusions As previously reported, we confirm that significant differences exist between children and adults with respect to celecoxib disposition. We also show that food co-administration increases systemic exposure. Additionally, CYP2C9 genotyping in this small group of patients correlates well with the PK variation observed especially in the CYP2C9*3*3 patient who demonstrated a drastically reduced clearance capability. Clinical Pharmacology & Therapeutics (2004) 75, P31–P31; doi: 10.1016/j.clpt.2003.11.118 n tmax (h) Cmax (μg/L) AUC0-∞ (μg/L·h) t1/2 (h) Single dose-no food 21 3 1287.9±858.6 9201.9±5699.3 4.9±1.9 SS-no food 16 3 1439.8±755.6 11007.0±5201.2 5.0±2.4 Single dose-with food 3 3 2628.8±996.0 11546.4±1291.4 3.5±0.8 SS-with food 3 3 2439.8±912.8 13551.6±354.4 4.0±0.2 Single dose-CYP2C9*3*3 1 3 2940.4 108250.6 29.9 SS-CYP2C9*3*3 1 3 8468.7 549212.5 41.2