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 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--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 GI tract. This would minimize the effect of food on absorption; as such, patients with arthritis can be given celecoxib with or without food.
Paulson
S K
SK
Department of Clinical Pharmacokinetics and Bioavailability, Pharmacia, Skokie, Illinois 60077, USA. susan.k.paulson@pharmacia.com
Vaughn
M B
MB
Jessen
S M
SM
Lawal
Y
Y
Gresk
C J
CJ
Yan
B
B
Maziasz
T J
TJ
Cook
C S
CS
Karim
A
A
D000328:Adult; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D000068579:Celecoxib; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000494:pharmacology; D004285:Dogs; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D008297:Male; D011720:Pyrazoles; D013449:Sulfonamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004041:Dietary Fats; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib