TREATMENT OF A DISEASE OF THE GASTROINTESTINAL TRACT WITH AN IMMUNOSUPPRESSANT

1 . A method of treating a disease of the gastrointestinal (GI) tract in a subject, the method comprising orally administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of an immunosuppressant and topically delivering the therapeutically effective amount of the immunosuppressant to a desired location in the GI tract of the subject.

2 . The method of claim 1 , wherein the delivery of the therapeutically effective amount of the immunosuppressant at the desired location in the GI tract provides a concentration of the immunosuppressant in the plasma of the subject that is less than 1 μg/ml.

3 . The method of claim 1 , wherein the delivery of the therapeutically effective amount of the immunosuppressant at the desired location in the GI tract provides a concentration of the immunosuppressant in the plasma of the subject that is less than 0.3 μg/ml.

4 . The method of claim 1 , wherein the delivery of the therapeutically effective amount of the immunosuppressant at the desired location in the GI tract provides a concentration of the immunosuppressant in the plasma of the subject that is less than 0.1 μg/ml.

5 . The method of claim 1 , wherein the delivery of the therapeutically effective amount of the immunosuppressant at the desired location in the GI tract provides a concentration of the immunosuppressant in the plasma of the subject that is less than 0.01 μg/ml.

6 . The method of claim 1 , wherein the delivery of the therapeutically effective amount of the immunosuppressant results in a decrease of at least one biomarker in the GI tract, wherein the at least one biomarker is selected from the group consisting of interferon-γ, IL-β, IL-6, IL-22, IL-17A, TNFa, IL-2, and combinations thereof.

7 . The method of claim 1 , wherein the pharmaceutical composition is administered in an ingestible device.

8 . The method of claim 1 , wherein the therapeutically effective amount of the immunosuppressant is not therapeutic effective if administered systemically.

9 . The method of claim 1 , wherein the concentration of the immunosuppressant delivered at the desired location in the gastrointestinal tract is 10%, 25%, 50%, 75%, 100%, 200%, 300%, 400%, 500%, 1000%, 2000% greater than the concentration of immunosuppressant in plasma.

10 . The method of claim 9 , wherein the concentration of the immunosuppressant delivered at the desired location in the gastrointestinal tract is measured from a sample comprising GI tissue.

11 . The method of claim 9 , wherein the level of immunosuppressant in plasma in a subject at a time point following oral administration of the device is lower than the level of the immunosuppressant in plasma in a subject at substantially the same time point following systemic administration of an equal amount of the immunosuppressant.

12 . The method of claim 1 , wherein the desired location is proximate to one or more sites of disease.

13 . The method of claim 12 , wherein the immunosuppressant is delivered 100 cm or less from the one or more sites of disease.

14 . The method of claim 1 , wherein the immunosuppressant is delivered at the cecum, the ascending colon, or the distal portion of the ileum.

15 . The method of claim 1 , wherein the disease of the GI tract is an inflammatory bowel disease.

16 . The method of claim 1 , wherein the immunosuppressant is a calcineurin inhibitor.

17 . The method of claim 16 , wherein the immunosuppressant is selected from cyclosporine A, tacrolimus, or generic equivalents thereof.

18 . The method of claim 1 , wherein the pharmaceutical composition is a solution.

19 . The method of claim 1 , wherein the pharmaceutical composition is a suspension.

20 . The method of claim 1 , wherein delivery of the therapeutically effective amount of the Immunosuppressant at the desired location in the GI tract does not comprise releasing more than 10% of the immunosuppressant at a location that is not proximate to a site of disease.