Methods of using (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione
Stereomerically pure (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, substantially free of its (−) isomer, and prodrugs, metabolites, polymorphs, salts, solvates, hydrates, and clathrates thereof are discussed. Also discussed are methods of using and pharmaceutical compositions comprising the (+) enantiomer of 2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione are disclosed. The methods include methods of treating and/or preventing disorders ameliorated by the reduction of levels of TNF-α or the inhibition of PDE4.
1. A method of treating an autoimmune disease, the method comprising administering to a patient having the autoimmune disease a therapeutically effective amount of stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl) -2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione.
2. The method of claim 1 further comprising administering to the patient a therapeutically effective amount of an antihistamine, anti-inflammatory drug, non-steroid anti-inflammatory drug, or steroid.
3. The method of claim 1 wherein the patient is a mammal.
4. The method of claim 1 wherein the compound is administered parenterally, transdermally, mucosally, nasally, buccally, sublingually, or orally.
5. The method of claim 4 wherein the compound is administered orally.
6. The method of claim 5 wherein the compound is administered orally in a tablet or capsule form.
7. The method of claim 1 wherein the therapeutically effective amount is from about 1 mg to about 1000 mg per day.
8. The method of claim 7 wherein the therapeutically effective amount is from about 5 mg to about 500 mg per day.
9. The method of claim 8 wherein the therapeutically effective amount is from about 10 mg to about 200 mg per day.
10. The method of claim 2 wherein the non-steroid anti-inflammatory drug is selected from aspirin, salicylates, acetominophen, indomethacin, sulindac, etodolac, fenamates, tolmetin, ketorolac, diclofenac, ibuprofen, naproxen, fenoprofen, ketoprofen, flurbiprofen, oxaprozin, piroxicam, meloxicam and a pyrazolon derivative.
11. The method of claim 5 , wherein the compound is administered twice daily in equally divided doses.
12. The method of claim 5 , wherein the stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione comprises greater than about 90% by weight of (+) isomer based on the total weight percent of the compound.
13. The method of claim 5 , wherein the stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione comprises greater than about 95% by weight of (+) isomer based on the total weight percent of the compound.
14. The method of claim 5 , wherein the stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione comprises greater than about 97% by weight of (+) isomer based on the total weight percent of the compound.
15. The method of claim 6 , wherein the capsule contains about 10 mg of the compound.
16. The method of claim 6 , wherein the capsule contains about 20 mg of the compound.
17. The method of claim 6 , wherein the capsule contains about 25 mg of the compound.
18. The method of claim 6 , wherein the capsule contains about 50 mg of the compound.
19. The method of claim 6 , wherein the tablet contains about 10 mg of the compound.
20. The method of claim 6 , wherein the tablet contains about 20 mg of the compound.
21. The method of claim 6 , wherein the tablet contains about 25 mg of the compound.
22. The method of claim 6 , wherein the tablet contains about 50 mg of the compound.
23. The method of claim 1 , wherein the stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione comprises about 98.7% by weight of (+) isomer based on the total weight percent of the compound.
24. The method of claim 23 , wherein the compound is administered orally in a tablet form.
25. The method of claim 24 , wherein the tablet is administered twice daily in equally divided doses.
26. The method of claim 25 , wherein the tablet contains about 10 mg of the compound.
27. The method of claim 25 , wherein the tablet contains about 20 mg of the compound.
28. The method of claim 24 , wherein the tablet is administered in a single, once-a-day dose.
29. The method of claim 28 , wherein the tablet contains about 100 mg of the compound.
30. The method of claim 24 , wherein the therapeutically effective amount is from about 1 mg to about 1000 mg per day.
31. The method of claim 24 , wherein the therapeutically effective amount is from about 5 mg to about 500 mg per day.
32. The method of claim 24 , wherein the therapeutically effective amount is from about 10 mg to about 200 mg per day.
33. The method of claim 24 , wherein the therapeutically effective amount is about 100 mg per day.