Celecoxib-tramadol co-crystal: A Randomized 4-Way Crossover Comparative Bioavailability Study.

Area of Science:

• Pharmacology
• Drug Development
• Clinical Pharmacology

Background:

• Celecoxib-tramadol co-crystal (CTC) represents a novel formulation combining celecoxib and racemic tramadol.
• Understanding the pharmacokinetic (PK) profile of CTC is crucial for its clinical application.

Purpose of the Study:

• To compare the single-dose PK parameters of CTC with individual immediate-release celecoxib and tramadol products.
• To assess the systemic exposure of celecoxib and tramadol when administered as a co-crystal versus concomitant administration.

Main Methods:

• A single-center, randomized, open-label, 4-period crossover study in healthy subjects.
• Subjects received CTC, tramadol alone, celecoxib alone, or celecoxib plus tramadol.
• Key PK parameters including Cmax, AUC0-T, and AUC0-∞ were measured and analyzed.

Main Results:

• Celecoxib from CTC showed a lower Cmax, reduced AUCs, and faster Tmax compared to co-administration.
• Tramadol and its active metabolite O-desmethyl tramadol from CTC exhibited lower Cmax and AUCs with a longer Tmax.
• Adverse events were more frequent with separate administration of tramadol and celecoxib.

Conclusions:

• Co-crystallization of celecoxib and tramadol favorably modified PK parameters, ensuring comparable systemic exposure to individual agents.
• CTC effectively minimized absorption interference seen with concomitant celecoxib and tramadol administration.
• The study validated the dosing regimen for CTC for future Phase 3 trials.