COMPOSITIONS FOR ORAL ADMINISTRATION OF ZOLEDRONIC ACID OR RELATED COMPOUNDS FOR TREATING COMPLEX REGIONAL PAIN SYNDROME
Oral dosage forms of osteoclast inhibitors, such as zoledronic acid, in an acid or a salt form 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; wherein the amount of zoledronic acid in an acid or a salt form in a single dose is about 40 mg to about 300 mg; wherein the pill, tablet, or capsule is orally administered to a human being suffering from complex regional pain syndrome at an interval of about 1 to 21 days.
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 an 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 the single dose of the zoledronic acid 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 the single dose of the zoledronic acid 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 the single dose of the zoledronic acid 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 zoledronic acid is administered approximately weekly.
12 . The method of claim 11 , wherein the zoledronic acid is administered 6 times.
13 . The method of claim 12 , wherein the complex regional pain syndrome is associated with an 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 an 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; wherein the amount of zoledronic acid in a single dose is about 100 mg to about 200 mg; and wherein the pill, tablet, or capsule is orally administered to a human being suffering from complex regional pain syndrome at an interval of 5 to 30 days.
17 . The method of claim 16 , wherein the zoledronic acid is in an acid form.
18 . The method of claim 16 , 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 16 , 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 16 , 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 16 , 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 16 , wherein the single dose of the zoledronic acid results in an AUC for zoledronic acid of about 130 ng·hr/mL to about 160 ng·hr/mL.
24 . The method of claim 16 , wherein the single dose of the zoledronic acid results in an AUC for zoledronic acid of about 300 ng·hr/mL to about 350 ng·hr/mL.
25 . The method of claim 16 , wherein the single dose of the zoledronic acid results in an AUC for zoledronic acid of about 405 ng·hr/mL to about 450 ng·hr/mL.
26 . The method of claim 16 , wherein the zoledronic acid is orally administered in a dosage form that further comprises magnesium stearate.
27 . The method of claim 16 , wherein the complex regional pain syndrome is associated with an inciting event, and the inciting event is a fracture.
28 . The method of claim 16 , 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 16 , wherein the zoledronic acid is orally administered three times within a period of six months.
30 . The method of claim 29 , wherein the zoledronic acid is orally administered at an interval of about 2 weeks.