Pharmacokinetics of celecoxib after oral administration in dogs and humans: Effect of food and site of absorption

Celecoxib pharmacokinetics was evaluated after single and multiple oral dos ing; after dosing in a solution and as a solid; with and without food; and after administration into different sites of the GI tract using dog. After oral dosing in a solution, celecoxib was rapidly absorbed and reached maxim um concentrations by 1 h; absorption was delayed another 1 to 2 h when admi nistered as a solid. The absolute bioavailability of celecoxib was higher w hen given as a solution (64-88%) compared with capsule (22-40%). The absorp tion of celecoxib given in a capsule was delayed by food, although systemic exposure increased by 3- to 5-fold. The systemic availability of celecoxib given intragastrically in solution was similar to that obtained following direct instillation into the duodenum, jejunum, or colon through a chronic intestinal access port. Collectively, these data suggest that celecoxib is a highly permeable drug that can be absorbed throughout the GI tract and th at dissolution may be a rate-limiting factor for absorption from solid dosa ge forms. Unlike dogs, celecoxib given to humans with a high fat meal exhib its only a slight increase in AUC(0-infinity) (11%) that is not clinically significant with regard to safety or efficacy. In humans, a lower dose and a longer GI residence time may promote the opportunity for absorption of a poorly soluble drug such as celecoxib that can be absorbed throughout the G I tract. This would minimize the effect of food on absorption; as such, pat ients with arthritis can be given celecoxib with or without food.