Compositions for oral administration of zoledronic acid or related compounds for treating complex regional pain syndrome
Oral dosage forms of osteoclast inhibitors, such as nitrogen-containing bisphosphonates, can be used to treat or alleviate pain or related conditions such as complex regional pain syndrome.
1. A method of safely and effectively treating complex regional pain syndrome by delivering zoledronic acid to the blood through repeated oral administration comprising: mixing zoledronic acid with a diluent, binder, disintegrating agent, or lubricant to form a pharmaceutical composition; forming the pharmaceutical composition into a pill, tablet, or capsule containing at least 10% zoledronic acid by weight, and containing about 30 mg to about 300 mg of zoledronic acid in the acid or a sodium salt form; and orally administering the pill, tablet, or capsule to a human being suffering from complex regional pain syndrome at least twice a month and no more frequently than once a day.
2. The method of claim 1 , wherein the zoledronic acid is in a salt form.
3. The method of claim 1 , wherein the zoledronic acid is in an acid form.
4. The method of claim 1 , wherein the complex regional pain syndrome is associated with inciting event.
5. The method of claim 4 , wherein the inciting event is a fracture.
6. The method of claim 1 , wherein the AUC of zoledronic acid in the human being, measured over a period of one month, is about 100 ng·h/mL to about 500 ng·h/mL.
7. The method of claim 1 , wherein the AUC of zoledronic acid in the human being, measured over a period of one month, is about 500 ng·h/mL to about 1000 ng·h/mL.
8. The method of claim 1 , wherein a single oral administration of the dosage form results in an AUC for zoledronic acid of about 130 ng·hr/mL to about 160 ng·hr/mL.
9. The method of claim 1 , wherein a single oral administration of the dosage form results in an AUC for zoledronic acid of about 300 ng·hr/mL to about 350 ng·hr/mL.
10. The method of claim 1 , wherein a single oral administration of the dosage form results in an AUC for zoledronic acid of about 405 ng·hr/mL to about 450 ng·hr/mL.
11. The method of claim 1 , wherein the dosage form is administered approximately weekly.
12. The method of claim 11 , wherein the dosage form is administered 6 times.
13. The method of claim 12 , wherein the complex regional pain syndrome is associated with inciting event, and the inciting event is a fracture.
14. The method of claim 13 , wherein, at the beginning of treatment, the human being has an average weekly pain intensity of at least 5 on the 0-10 numeric rating scale.
15. The method of claim 8 , wherein the complex regional pain syndrome is associated with inciting event, and the inciting event is a fracture, and at the beginning of treatment, the human being has an average weekly pain intensity of at least 5 on the 0-10 numeric rating scale.
16. A method of safely and effectively treating complex regional pain syndrome by delivering zoledronic acid to the blood through repeated oral administration comprising: mixing zoledronic acid with a diluent, binder, disintegrating agent, or lubricant to form a pharmaceutical composition; forming the pharmaceutical composition into a pill, tablet, or capsule containing at least 10% zoledronic acid by weight, and containing about 100 mg to about 250 mg of zoledronic acid; and orally administering the pill, tablet, or capsule to a human being suffering from complex regional pain syndrome at least twice a month and no more frequently than once a day.
17. The method of claim 15 , wherein the zoledronic acid is in an acid form.
18. The method of claim 15 , wherein the zoledronic acid is in a salt form.
19. The method of claim 18 , wherein the imidazole ring of zoledronic acid is in an imidazolium form.
20. The method of claim 15 , wherein the zoledronic acid is orally administered in at least two consecutive doses that are at least about 1 week apart.
21. The method of claim 15 , wherein the AUC of zoledronic acid in the human being, measured over a period of one month, is about 100 ng·h/mL to about 500 ng·h/mL.
22. The method of claim 15 , wherein the AUC of zoledronic acid in the human being, measured over a period of one month, is about 500 ng·h/mL to about 1000 ng·h/mL.
23. The method of claim 15 , wherein a single oral administration of the dosage form results in an AUC for zoledronic acid of about 130 ng·hr/mL to about 160 ng·hr/mL.
24. The method of claim 15 , wherein a single oral administration of the dosage form results in an AUC for zoledronic acid of about 300 ng·hr/mL to about 350 ng·hr/mL.
25. The method of claim 15 , wherein a single oral administration of the dosage form results in an AUC for zoledronic acid of about 405 ng·hr/mL to about 450 ng·hr/mL.
26. The method of claim 15 , wherein the zoledronic acid is orally administered in a dosage form that further comprises magnesium stearate.
27. The method of claim 15 , wherein the complex regional pain syndrome is associated with inciting event, and the inciting event is a fracture.
28. The method of claim 15 , wherein, at the beginning of treatment, the human being has an average weekly pain intensity of at least 5 on the 0-10 numeric rating scale.
29. The method of claim 15 , wherein the dosage form is orally administered three times within a period of six months.
30. The method of claim 29 , wherein the dosage form is orally administered at an interval of about 2 weeks.