Abstract
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 AUC0–∞ (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.
Footnotes
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Send reprint requests to: Susan K. Paulson, Ph.D., Pharmacia, 4901 Searle Pkwy., Skokie, IL 60077. E-mail:susan.k.paulson{at}pharmacia.com
- Abbreviations:
- NSAID
- nonsteroidal anti-inflammatory drug
- COX
- cyclooxygenase
- EM
- extensive metabolizer
- PM
- poor metabolizer
- GI
- gastrointestinal
- CIAP
- chronic intestinal access port
- Cmax
- observed peak plasma concentration
- Tmax
- time to peak plasma concentration
- AUC
- area under the plasma concentration-time curve
- BA
- bioavailability
- IG
- intragastrically
- Received November 15, 2000.
- Accepted January 22, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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