Methods for the safe administration of imidazole or imidazolium compounds
Methods for the safe administration of imidazole or imidazolium compounds such as zoledronic acid, and conditions that may be treated by these methods, are described herein.
1. A method of safely and effectively delivering zoledronic acid to the blood of a human being through repeated oral administration comprising:
orally administering a pharmaceutical composition comprising the zoledronic acid to the human being at least once a month and no more frequently than once a day;
wherein the pharmaceutical composition is formed by mixing the zoledronic acid with a diluent, a binder, an excipient, a disintegrating agent, a flavoring agent, or a lubricant, and the pharmaceutical composition contains at least 10% zoledronic acid and less than 10% carboxylic acid salt enhancer by weight;
wherein the pharmaceutical composition is in the form of a pill, a tablet, or a capsule, and each dose of the pharmaceutical composition contains about 0.11 millimoles to about 1.1 millimoles of the zoledronic acid, in an acid or a salt form; and
wherein the delivered pharmaceutical composition provides zoledronic acid with an oral bioavailability of 1.1% to 2.3% to the blood of the human being, wherein the human being is in a fasted state.
2. The method of claim 1 , wherein about 0.17 millimoles to about 0.20 millimoles of the zoledronic acid is orally administered weekly.
3. The method of claim 2 , wherein the pill, the tablet, or the capsule containing the zoledronic acid is orally administered for about 6 weeks.
4. The method of claim 1 , wherein about0.5 millimoles to about 0.7 millimoles of the zoledronic acid is orally administered 2 or 3 times a month.
5. The method of claim 1 , wherein the pharmaceutical composition is orally administered to the human being to treat complex regional pain syndrome (CRPS).
6. The method of claim 5 , wherein the CRPS is CRPS type I.
7. The method of claim 5 , wherein the CRPS is precipitated by fracture.
8. The method of claim 1 , wherein the pharmaceutical composition is orally administered to the human being to treat arthritis.
9. The method of claim 1 , wherein the pharmaceutical composition is orally administered to the human being to treat back pain.
10. The method of claim 1 , wherein the pharmaceutical composition is orally administered to the human being to treat knee pain.
11. The method of claim 1 , wherein oral administration of each dose of the pharmaceutical composition results in a decrease of osteoclast activity by at least about 5% in the human being.
12. The method of claim 1 , wherein oral administration of each dose of the pharmaceutical composition results in a decrease of osteoclast activity by at least about 15% in the human being.
13. The method of claim 1 , wherein oral administration of each dose of the pharmaceutical composition results in a decrease of osteoclast activity by at least about 35% in the human being.
14. The method of claim 1 , wherein oral administration of each dose of the pharmaceutical composition results in a decrease of osteoclast activity by at least about 55% in the human being.
15. The method of claim 1 , wherein oral administration of each dose of the pharmaceutical composition results in a decrease of osteoclast activity by about 60% to about 80% in the human being.
16. The method of claim 1 , wherein oral administration of each dose of the pharmaceutical composition results in a decrease of osteoclast activity by about 80% to about 90% in the human being.
17. The method of claim 1 , wherein oral administration of each dose of the pharmaceutical composition results in a decrease of osteoclast activity by about 90% to about 100% in the human being.
18. The method of claim 1 , wherein oral administration of each dose of the pharmaceutical composition results in a decrease in CTX serum levels by at least about 10% in the human being.
19. The method of claim 1 , wherein oral administration of each dose of the pharmaceutical composition results in a decrease in CTX serum levels by at least about 30% in the human being.
20. The method of claim 1 , wherein oral administration of each dose of the pharmaceutical composition results in a decrease in CTX serum levels by at least about 50% in the human being.
21. The method of claim 1 , wherein oral administration of each dose of the pharmaceutical composition results in a decrease in CTX serum levels by about 60% to about 80% in the human being.
22. The method of claim 1 , wherein oral administration of each dose of the pharmaceutical composition results in a decrease in CTX serum levels by about 80% to about 90% in the human being.
23. The method of claim 1 , wherein oral administration of each dose of the pharmaceutical composition results in a decrease in CTX serum levels by at least about 95% in the human being.
24. The method of claim 1 , wherein the zoledronic acid in the pharmaceutical composition is in a disodium salt form.
25. The method of claim 1 , wherein the delivered pharmaceutical composition provides zoledronic acid with an oral bioavailability of 1.1% to 2.2% to the blood of the human being, wherein the human being is in a fasted state.
26. The method of claim 1 , wherein the delivered pharmaceutical composition provides zoledronic acid with an oral bioavailability of 1.1% to 2% to the blood of the human being, wherein the human being is in a fasted state.
27. The method of claim 1 , wherein the delivered pharmaceutical composition provides zoledronic acid with an oral bioavailability of 1.1% to 1.5% to the blood of the human being, wherein the human being is in a fasted state.