Vol. 297, Issue 2, 638-645, May 2001

Pharmacokinetics of Celecoxib after Oral Administration in Dogs and Humans: Effect of Food and Site of Absorption

Susan K. Paulson , Margaret B. Vaughn, Susan M. Jessen, Yvette Lawal, Christopher J. Gresk, Bo Yan, Timothy J. Maziasz, Chyung S. Cook and Aziz Karim

Departments of Clinical Pharmacokinetics and Bioavailability (S.K.P., A.K.), Metabolism and Safety Evaluation (S.K.P., C.J.G., C.S.C.), Pharmaceutical Sciences (M.B.V.), Regulatory Affairs (S.M.J.), Information Resources (Y.L.), Statistics (B.Y.), and COX-2 Technology (T.J.M.), Pharmacia, Skokie, Illinois

Celecoxib pharmacokinetics was evaluated after single and multiple oral dosing; 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 maximum concentrations by 1 h; absorption was delayed another 1 to 2 h when administered as a solid. The absolute bioavailability of celecoxib was higher when given as a solution (64-88%) compared with capsule (22-40%). The absorption 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 that dissolution may be a rate-limiting factor for absorption from solid dosage forms. Unlike dogs, celecoxib given to humans with a high fat meal exhibits only a slight increase in AUC_0- (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 GI tract. This would minimize the effect of food on absorption; as such, patients with arthritis can be given celecoxib with or without food.