Methods of optimizing drug therapeutic efficacy for treatment of immune ...

1. A method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising:

(a) administering a drug providing 6-thioguanine to a subject having said immune-mediated gastrointestinal disorder; and

(b) determining a level of 6-thioguanine or 6-methyl-mercaptopurine in said subject having said immune-mediated gastrointestinal disorder,

wherein a level of 6-thioguanine less than about 230 pmol per 8108 red blood cells indicates a need to increase the amount of said drug subsequently administered to said subject and

wherein a level of 6-thioguanine greater than about 400 pmol per 8108 red blood cells or a level of 6-methyl-mercaptopurine greater than about 7000 pmol per 8108 red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject.

2. The method of claim 1, wherein said immune-mediated gastrointestinal disorder is inflammatory bowel disease (IBD).

3. The method of claim 2, wherein said subject having IBD is a pediatric subject.

4. The method of claim 1, wherein said immune-mediated gastrointestinal disorder is selected from the group consisting of lymphocytic colitis, microscopic colitis, collagenous colitis, autoimmune enteropathy, allergic gastrointestinal disease and eosinophilic gastrointestinal disease.

5. The method of claim 1, wherein said level of 6-thioguanine is determined in red blood cells.

6. The method of claim 5, wherein said level is determined using high pressure liquid chromatography.

7. A method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising determining the level of 6-thioguanine or 6-methyl-mercaptopurine in a subject administered a drug providing 6-thioguanine, said subject having said immune-mediated gastrointestinal disorder,

wherein the level of 6-thioguanine less than about 230 pmol per 8108 red blood cells indicates a need to increase the amount of said drug subsequently administered to said subject, and wherein the level of 6-thioguanine greater than about 400 pmol per 8108 red blood cells or a level of 6-methyl-mercaptopurine greater than about 7000 pmol per 8108 red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject wherein said decrease reduces toxicity.

8. The method of claim 7, wherein said immune-mediated gastrointestinal disorder is IBD.

9. The method of claim 8, wherein said subject having IBD is a pediatric subject.

10. The method of claim 7, wherein said immune-mediated gastrointestinal disorder is lymphocytic colitis.

11. The method of claim 7, wherein said immune-mediated gastrointestinal disorder is microscopic colitis.

12. The method of claim 7, wherein said immune-mediated gastrointestinal disorder is collagenous colitis.

13. The method of claim 7, wherein said immune-mediated gastrointestinal disorder is autoimmune enteropathy.

14. The method of claim 7, wherein said immune-mediated gastrointestinal disorder is allergic gastrointestinal disease.

15. The method of claim 7, wherein said immune-mediated gastrointestinal disorder is eosinophilic gastrointestinal disease.

16. The method of claim 7, wherein said level of 6-thioguanine and said level of 6-methyl-mercaptopurine each is determined in red blood cells.

17. The method of claim 16, wherein said level is determined using high pressure liquid chromatography.

18. The method of claim 7, wherein said toxicity is hepatic toxicity.

19. The method of claim 7, wherein said toxicity is hematologic toxicity.

20. The method of claim 7, wherein said drug is 6 -mercaptopurine.

21. The method of claim 7, wherein said drug is azathioprine.

22. The method of claim 7, wherein said drug is 6-thioguanine.

23. The method of claim 7, wherein said drug is 6-methylmercaptopurine riboside.

24. A method of optimizing therapeutic efficacy for treatment of an autoimmune disease, comprising determining the level of 6-thioguanine or 6-methyl-mercaptopurine in a subject administered a drug providing 6-thioguanine, said subject having said autoimmune disease,

wherein the level of 6-thioguanine less than about 230 pmol per 8108 red blood cells indicates a need to increase the amount of said drug subsequently administered to said subject, and wherein the level of 6-thioguanine greater than about 400 pmol per 8108 red blood cells or a level of 6-methyl-mercaptopurine greater than about 7000 pmol per 8108 red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject wherein said decrease reduces toxicity.

25. The method of claim 24, wherein said level of 6-thioguanine and said level of 6-methyl-mercaptopurine each is determined in red blood cells.

26. The method of claim 25, wherein said level is determined using high pressure liquid chromatography.

27. The method of claim 24, wherein said toxicity is hepatic toxicity.

28. The method of claim 24, wherein said toxicity is hematologic toxicity.

29. The method of claim 24, wherein said drug is 6 -mercaptopurine.

30. The method of claim 24, wherein said drug is azathioprine.

31. The method of claim 24, wherein said drug is 6-thioguanine.

32. The method of claim 24, wherein said drug is 6 -methylmercaptopurine riboside.