Effects of Dual Cyclooxygenase-2 and Carbonic Anhydrase Inhibition

Exclusion Criteria

• •1. Use of any non-study medication(s) including low dose aspirin for cardiovascular prophylaxis within 2 weeks prior and 2 weeks after receipt of each dose of study drug;
• •2. Use of chemotherapy agents or history of cancer, other than non-metastatic skin cancer that has been completely excised, within five (5) years prior to the screening visit;
• •3. History of bacterial or viral infection requiring treatment with antibiotics or antivirals within 3 months of study;
• •4. Presence or history of peripheral edema within the past 5 years;
• •5. History of congestive heart failure;
• •6. Use of drugs which are P450 3A4 inducers or inhibitors within the past 30 days (e.g. alprazolam, chlorpheniramine, cimetidine, fluoxetine, haloperidol, ketoconazole, itraconazole, erythromycin, clarithromycin, sildenafil, simvastatin, St. John's Wort);
• •7. Use of prescribed systemic or topical medications or any dietary aids or foods that are known to modulate drug metabolizing enzymes (e.g. grapefruit juice) within 14 days of dose administration;
• •8. Difficulty in swallowing oral medications;
• •9. History of seizure disorder;
• •10. Serious psychosocial co-morbidities;
• •11. Cognitive or psychiatric disorders, or any other condition that could interfere with compliance with study procedures and/or confinement in a clinical study unit for 2 days or longer;
• •12. History of drug or alcohol abuse within one year prior to screening;
• •13. Use of any other investigational drug within 1 month prior to enrollment;
• •14. Use of any prescription drugs within 1 month prior to enrollment;
• •15. Use of over the counter medication excluding routine vitamins, but including mega-dose vitamin therapy, within one week of enrollment;
• •16. Donation and/or receipt of any blood or blood products within 3 months prior to enrollment;
• •17. Active gastrointestinal, renal, hepatic, or coagulant disorder within 1 month prior to enrollment;
• •18. Esophageal or gastroduodenal ulceration within 1 month prior to enrollment;
• •19. Hypersensitivity to NSAIDs, sulfonamides, COX-2 inhibitors, or carbonic anhydrase inhibitors;
• •20. Known allergy or hypersensitivity to sulfa drugs;
• •21. Family history of significant cardiac disease (i.e. sudden death in first degree relative; myocardial infarction prior to 50 years old);
• •22. Occult blood in stool (fecal occult blood test).