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 delivering zoledronic acid to blood comprising orally administering a dosage form to a human being in need of treatment with zoledronic acid, wherein the dosage form comprises:
a) zoledronic acid which is free of Ion 1 and Ion 2; or
b) one of the following:
1) zoledronic acid and
in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; or
2) zoledronic acid and
in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w; or
3) zoledronic acid and a combination of Ion 1 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w, and Ion 2 in a salt form, in an amount that is less than 0.1% w/w and greater than 0% w/w;
wherein any amount in % w/w is based upon the total weight of the zoledronic acid, Ion 1, Ion 2, and any corresponding counter ions; and
wherein, prior to administration of the dosage form, the mean bioavailability of the zoledronic acid in the dosage form has been shown to be about 1.1% to about 4% in human subjects, wherein the human subjects have fasted for at least 2 hours.
2. The method of claim 1 , wherein, prior to administration of the dosage form, the mean bioavailability of zoledronic acid in the dosage form has been shown to be about 2% to about 2.5% in human subjects.
3. The method of claim 1 , wherein, prior to administration of the dosage form, the mean bioavailability of zoledronic acid in the dosage form has been shown to be about 1.1% to about 2.5% in human subjects.
4. The method of claim 1 , wherein, prior to administration of the dosage form, the mean bioavailability of zoledronic acid in the dosage form has been shown to be about 1.1% to about 2.4% in human subjects.
5. The method of claim 1 , wherein, prior to administration of the dosage form, the mean bioavailability of zoledronic acid in the dosage form has been shown to be about 2.2% to about 2.4% in human subjects.
6. The method of claim 1 , wherein, prior to administration of the dosage form, the mean bioavailability of zoledronic acid in the dosage form has been shown to be about 2% to about 2.2% in human subjects.
7. The method of claim 1 , wherein, prior to administration of the dosage form, the mean bioavailability of zoledronic acid in the dosage form has been shown to be about 1.8% to about 2% in human subjects.
8. The method of claim 1 , wherein, prior to administration of the dosage form, the mean bioavailability of zoledronic acid in the dosage form has been shown to be about 1.6% to about 1.8% in human subjects.
9. The method of claim 1 , wherein, prior to administration of the dosage form, the mean bioavailability of zoledronic acid in the dosage form has been shown to be about 1.5% to about 1.6% in human subjects.
10. The method of claim 1 , wherein, prior to administration of the dosage form, the mean bioavailability of zoledronic acid in the dosage form has been shown to be about 1.4% to about 1.5% in human subjects.
11. The method of claim 1 , wherein, prior to administration of the dosage form, the mean bioavailability of zoledronic acid in the dosage form has been shown to be about 1.3% to about 1.4% in human subjects.
12. The method of claim 1 , wherein, prior to administration of the dosage form, the mean bioavailability of zoledronic acid in the dosage form has been shown to be about 1.2% to about 1.3% in human subjects.
13. The method of claim 1 , wherein, prior to administration of the dosage form, the mean bioavailability of zoledronic acid in the dosage form has been shown to be about 1.1% to about 1.2% in human subjects.
14. The method of claim 1 , wherein, prior to oral administration of the dosage form, oral administration of the dosage form to human subjects in a fasted state has been shown to result in a mean area under the plasma concentration curve (AUC) of zoledronic acid of about 50 ng·hr/mL to about 500 ng·hr/mL, measured over a 24-hour period.
15. The method of claim 1 , wherein, prior to oral administration of the dosage form, oral administration of the dosage form to human subjects in a fasted state has been shown to result in a mean AUC of zoledronic acid of about 130 ng·hr/mL to about 180 ng·hr/mL, measured over a 24-hour period.
16. The method of claim 1 , wherein, prior to oral administration of the dosage form, oral administration of the dosage form to human subjects in a fasted state has been shown to result in a mean AUC of zoledronic acid of about 130 ng·hr/mL to about 140 ng·hr/mL, measured over a 24-hour period.
17. The method of claim 1 , wherein, prior to oral administration of the dosage form, oral administration of the dosage form to human subjects in a fasted state has been shown to result in a mean AUC of zoledronic acid of about 140 ng·hr/mL to about 150 ng·hr/mL, measured over a 24-hour period.
18. The method of claim 1 , wherein, prior to oral administration of the dosage form, oral administration of the dosage form to human subjects in a fasted state has been shown to result in a mean AUC of zoledronic acid of about 150 ng·hr/mL to about 200 ng·hr/mL, measured over a 24-hour period.
19. The method of claim 1 , wherein, prior to oral administration of the dosage form, oral administration of the dosage form to human subjects in a fasted state has been shown to result in a mean AUC of zoledronic acid of about 250 ng·hr/mL to about 300 ng·hr/mL, measured over a 24-hour period.
20. The method of claim 1 , wherein, prior to oral administration of the dosage form, oral administration of the dosage form to human subjects in a fasted state has been shown to result in a mean AUC of zoledronic acid of about 300 ng·hr/mL to about 350 ng·hr/mL, measured over a 24-hour period.
21. The method of claim 1 , wherein, prior to oral administration of the dosage form, oral administration of the dosage form to human subjects in a fasted state has been shown to result in a mean AUC of zoledronic acid of about 350 ng·hr/mL to about 400 ng·hr/mL, measured over a 24-hour period.
22. The method of claim 1 , wherein, prior to oral administration of the dosage form, oral administration of the dosage form to human subjects in a fasted state has been shown to result in a mean AUC of zoledronic acid of about 400 ng·hr/mL to about 500 ng·hr/mL, measured over a 24-hour period.
23. The method of claim 1 , wherein the dosage form contains about 50 mg to about 200 mg of the zoledronic acid.
24. The method of claim 1 , wherein the dosage form contains about 50 mg to about 60 mg of the zoledronic acid in a disodium salt form.
25. The method of claim 18 , wherein the dosage form contains about 100 mg to about 200 mg of the zoledronic acid in an acid form or a salt form.
26. The method of claim 1 , wherein the dosage form contains at least about 10% of zoledronic acid by weight.
27. The method of claim 1 , wherein the dosage form contains at least about 20% of zoledronic acid by weight.
28. A method of treating complex regional pain syndrome comprising orally administering a dosage form of claim 1 to a human being in need thereof.
29. The method of claim 28 , wherein the zoledronic acid in the dosage form is in a salt form.
30. The method of claim 29 , wherein the mean bioavailability of zoledronic acid in the dosage form has been shown to be about 1.1% to about 2% in human subjects.