Formulations and uses of 2-hydroxy-5-phenylazobenzoic acid derivatives

Abstract

A method of increasing the bioavailability of 5-aminosalicylate compound by administration of an oral dosage form with food is provided, as well as an article of manufacture comprising an oral dosage form of 5-aminosalicylate compound in a suitable container and associated with printed labeling which describes the increased bioavailability of the medication in the container when taken with food.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the pharmokinetic profiles of balsalazide and its key metabolites when administered to human subjects in the fasted and fed state.

FIG. 2 shows the ratio of plasma NASA to 5-ASA for C_max and AUC_last in the fasted and fed state.

Claims

1. A method of increasing the bioavailability of a 5-aminosalicylate compound comprising administering to the subject a therapeutically effective amount of the 5-aminosalicylate compound with food.

2. The method of claim 1, wherein the bioavailability of the 5-aminosalicylate compound is increased compared to administering the 5-aminosalicylate compound without food.

3. A method of increasing the bioavailability of 5-ASA to the colon of a subject comprising administering to a subject in need thereof a therapeutically effective amount of a 5-aminosalicylate compound with food.

4. The method of claim 3, wherein the bioavailability of 5-ASA is increased compared to administering the 5-aminosalicylate compound without food.

5. A method of delaying the transit of 5-ASA in the colon of a subject comprising, administering a therapeutically effective amount of a 5-aminosalicylate compound to a subject in need thereof with food.

6. The method of claim 5, wherein the transit of 5-ASA is increased compared to administering the 5-aminosalicylate compound without food.

7. A method for decreasing systemic level of 5-ASA in a subject comprising, administering to a subject in need thereof a therapeutically effective amount of a 5-aminosalicylate compound with food.

8. The method of claim 7, wherein the systemic level of 5-ASA is decreased compared to administering the 5-aminosalicylate compound without food.

9. A method of decreasing the maximal plasma concentration (Cmax) of a 5-aminosalicylate compound in a subject comprising, administering to a subject in need thereof a therapeutically effective amount of a 5-aminosalicylate compound with food.

10. The method of claim 9, wherein the Cmax of the 5-aminosalicylate compound is decreased compared to administering the 5-aminosalicylate without food.

11. A method of delaying Tmax of a 5-aminosalicylate compound in a subject comprising, administering to a subject in need thereof a therapeutically effective amount of a 5-aminosalicylate compound with food.

12. The method of claim 11, wherein the Tmax of the 5-aminosalicylate compound is delayed compared to administering the 5-aminosalicylate compound without food.

13. A method of decreasing the extent of absorption (AUClast) of a 5-aminosalicylate compound in a subject comprising, administering to a subject in need thereof a therapeutically effective amount of a 5-aminosalicylate compound with food.

14. The method of claim 13, wherein the AUClast of the 5-aminosalicylate compound is decreased compared to administering the 5-aminosalicylate compound without food.

15. A method of increasing the systemic ratio of NASA to 5-ASA in a subject comprising, administering to a subject in need thereof a therapeutically effective amount of a 5-aminosalicylate compound with food.

16. The method of claim 15, wherein the systemic ratio of NASA to 5-ASA is increased compared to administering the 5-aminosalicylate compound without food.

17. A method of increasing the conversion of 5-ASA to NASA in a subject comprising, administering to a subject in need thereof a therapeutically effective amount of a 5-aminosalicylate compound with food.

18. The method of claim 17, wherein the conversion of 5-ASA to NASA is increased in a subject administered a therapeutically effective amount of the 5-aminosalicylate compound compared to administering a 5-aminosalicylate without food.

19. The method of any one of claims 1-18, wherein the 5-aminosalicylate compound comprises one or more of mesalamine, sulphasalazine, olsalazine, ipsalazine, salicylazobenzoic acid, or balsalazide.

20. The method any one of claims 1-18, wherein the therapeutically effective amount comprises from between about 6.25 mg to about 7000 mg/day.

21. The method any one of claims 1-18, wherein the therapeutically effective amount comprises from between about 750 mg to about 6750 mg/day.

22. The method of any one of claims 1-18, wherein the therapeutically effective amount is a dosage regimen of three tablets of the formulation three times each day, wherein each tablet comprises about 750 mg of the 5-aminosalicylate compound.

23. The method of any one of claims 1-18, wherein the therapeutically effective amount is a dosage regimen of two tablets of the formulation three times each day, wherein each tablet comprises about 1125 mg of the 5-aminosalicylate compound.

24. The method any one of claims 1-18, wherein the therapeutically effective amount is a dosage regimen of one tablet three times each day, wherein each tablet comprises about 2250 mg of the 5-aminosalicylate compound.

25. The method of any one of claims 1-18, wherein the therapeutically effective amount is a dosage regime ranging from between about 1 to about 14 g per 70 kg body weight per day.

26. The method of any one of claims 1-18, wherein the administration to the subject occurs between about 30 minutes prior to about 2 hours after consuming food.

27. The method of any one of claims 1-18, wherein the administration to the subject is substantially at the same time as the consumption of the food.

28. The method of any one of claims 1-18, wherein the administration to the subject is immediately after the consumption of food up to about 1 hour after the consumption.

29. The method of any one of claims 1-18, wherein the therapeutically effective amount comprises a pharmaceutical composition in the form of a tablet, capsule, liquid, suspension, suppository or enema.

30. A method of decreasing the rate and extent of absorption of an oral dosage form of balsalazide as measured by the drug concentration or metabolite thereof attained in the blood stream over time in a subject comprising, administering to the subject a therapeutically effective amount of balsalazide in a pharmaceutical composition with food.

31. The method of claim 30, wherein the balsalazide is from a container comprising labeling advising that administration with food results in a decrease in the maximal plasma concentration (Cmax) and extent of absorption (AUClast) of balsalazide compared to administration without food.

32. A method of using balsalazide in the treatment of gastrointestinal disease comprising: informing a subject with a gastrointestinal disease that the administration of a therapeutically effective amount of balsalazide with food results in a decrease in at least one of Cmax, AUClast, or systemic adsorption of balsalazide compared to administration without food.

33. A method of using balsalazide in the treatment of gastrointestinal disorders comprising altering the oral bioavailability of balsalazide by: obtaining balsalazide from a container providing information that administration of balsalazide with food increases the bioavailability of balsalazide or a metabolite thereof to the colon of the subject compared to administration without food, and ingesting the balsalazide with food.

34. A method of using balsalazide in the treatment of gastrointestinal disorders comprising: administering to a subject in need of treatment a therapeutically effective amount of balsalazide, with food, wherein the administration of the balsalazide with food results in a decrease in at least one of Cmax and AUClast of balsalazide as compared to administration of balsalazide in a fasted state; and informing the subject that the administration of a therapeutically effective amount of balsalazide in a pharmaceutical composition with food results in one or more of a decrease in at least one of Cmax and AUClast of balsalazide compared to administration in a fasted state.

35. The method according to claim 34, wherein the balsalazide is from a container with printed labeling advising that administration with food results in a decrease in at least one of Cmax and AUClast of balsalazide compared to administration in a fasted state.

36. The method according to claim 35, wherein the balsalazide is provided in tablet form.

37. The method according to claim 36, wherein the balsalazide is provided in 750 mg tablet form.

38. The method according to claim 35, wherein the printed labeling advises that the administration of the balsalazide with food results in a decrease in the Cmax of about 10 to about 70%.

39. The method according to claim 35, wherein the printed labeling advises that the administration of the balsalazide with food results in a decrease in the AUClast of about 10 to about 70%.

40. The method according to claim 35, wherein the printed labeling further advises that the administration of the balsalazide with food results in an increase in a systemic ratio of NASA to 5-ASA of about 10 to about 100%.

41. A method of inhibiting the growth of a bacterial species in a human subject, comprising: administering to a human subject having a bacterial infection or overgrowth a pharmaceutically acceptable composition containing a 5-aminosalicylate compound in a dose effective to inhibit the growth of a bacterial species in the human subject with food.

42. The method of claim 41, wherein the 5-aminosalicylate compound is mesalamine, sulphasalazine, olsalazine, ipsalazine, salicylazobenzoic acid, balsalazide, or a conjugated bile acid.

43. The method of claim 42, wherein the bacterial species comprises one or more of a Clostridium species, an anaerobic bacteria or an aerobic bacteria.

44. The method of claim 43, wherein the Clostridium species is Clostridium perfringens, Clostridium difficile, Clostridium botulinum, or Clostridium tetani.