Compositions for oral administration of zoledronic acid or related compounds for treating Paget's disease of bone
View Patent ↗Oral dosage forms of bisphosphonate compounds, such as zoledronic acid, can be used to treat or alleviate pain or related conditions. The oral bioavailability of zoledronic acid can be enhanced by administering the zoledronic acid in the disodium salt form.
1. A method of treating Paget's disease of bone, comprising orally administering zoledronic acid in a disodium salt form to a mammal in need thereof, wherein the zoledronic acid in the disodium salt form is administered in an amount and frequency that results in an AUC of zoledronic acid, over a four week period, that is about 100 ng·h/mL to about 2000 ng·h/mL.
2. The method of claim 1 , wherein the zoledronic acid in the disodium salt form is administered in a dosage form that contains at least 10% w/w of zoledronic acid in the disodium salt form.
3. The method of claim 1 , wherein about 1 mg to about 600 mg of zoledronic acid in the disodium salt form is administered.
4. The method of claim 1 , wherein about 25 mg to about 500 mg of zoledronic acid in the disodium salt form is administered.
5. The method of claim 1 , wherein about 200 mg to about 300 mg of zoledronic acid in the disodium salt form is administered.
6. The method of claim 1 , wherein zoledronic acid in the disodium salt form is administered only once, or there is a period of about twenty-four hours to about two years between instances of administration of zoledronic acid in the disodium salt form.
7. The method of claim 1 , wherein there is a period of about twenty-four hours to about seven days between instances of administration of zoledronic acid in the disodium salt form.
8. The method of claim 1 , wherein there is a period of about seven days to about fourteen days between instances of administration of zoledronic acid in the disodium salt form.
9. The method of claim 1 , wherein there is a period of at least one month between instances of administration of zoledronic acid in the disodium salt form.
10. The method of claim 1 , wherein the zoledronic acid in the disodium salt form is administered in a solid dosage form.
11. The method of claim 10 , wherein the dosage form is a tablet or a capsule.
12. The method of claim 1 , wherein the zoledronic acid in the disodium salt form is administered in a solid dosage form that has a hardness of at least about 5 kPa.
13. The method of claim 1 , wherein the zoledronic acid in the disodium salt form is administered in a solid dosage form that contains about 10% w/w to about 90% w/w of zoledronic acid in the disodium salt form.
14. A method of treating Paget's disease of bone, comprising orally administering zoledronic acid in a disodium salt form to a mammal in need thereof, wherein the zoledronic acid in the disodium salt form is administered in an amount that results in an AUC of zoledronic acid that is about 20 ng·h/mL to about 700 ng·h/mL each time zoledronic acid is administered.
15. The method of claim 14 , wherein about 1 mg to about 600 mg of zoledronic acid in the disodium salt form is administered.
16. The method of claim 14 , wherein about 25 mg to about 300 mg of zoledronic acid in the disodium salt form is administered.
17. The method of claim 14 , wherein about 200 mg to about 300 mg of zoledronic acid in the disodium salt form is administered.
18. The method of claim 14 , wherein the mammal is a human being.
19. The method of claim 18 , wherein the zoledronic acid in the disodium salt form is administered to the human being after at least one hour of fasting.
20. The method of claim 18 , wherein the zoledronic acid in the disodium salt is administered to the human being after at least one half hour of fasting.
21. A method of treating Paget's disease of bone, comprising orally administering zoledronic acid to a human being in need thereof, wherein about 10 mg to about 600 mg of zoledronic acid in the disodium salt form is administered in an amount and frequency that results in a bioavailability of zoledronic acid in the human being of 1% to about 4%.
22. The method of claim 21 , wherein the zoledronic acid in the disodium salt form is administered in a manner that results in a bioavailability of zoledronic acid in the human being of 1.5% to 2%.
23. The method of claim 21 , wherein the zoledronic acid in the disodium salt form is administered in a manner that results in a bioavailability of zoledronic acid in the human being of 2% to 3%.
24. The method of claim 21 , wherein about 100 mg to about 400 mg of zoledronic acid in the disodium salt form is administered.
25. The method of claim 21 , wherein about 200 mg to about 300 mg of zoledronic acid in the disodium salt form is administered.
26. The method of claim 21 , wherein the zoledronic acid in the disodium salt form is administered in a dosage form that contains at least about 10% w/w to about 90% w/w of zoledronic acid in the disodium salt form.
27. The method of claim 21 , wherein the zoledronic acid in the disodium salt form is administered in three to eight divided doses.
28. The method of claim 21 , wherein the zoledronic acid in the disodium salt form is administered in three divided doses over a period of one to two months.
29. The method of claim 28 , wherein there is a period of at least one week between instances of administration of zoledronic acid in the disodium salt form.
30. The method of claim 28 , wherein there is a period of at least seven days to fourteen days between instances of administration of zoledronic acid in the disodium salt form.