Compositions for administration of zoledronic acid or related compounds for treating lower back pain
View Patent ↗Oral dosage forms of osteoclast inhibitors, such as nitrogen-containing bisphosphonates, such as zoledronic acid, can be used to treat or alleviate pain or related conditions.
1. A method of treating chronic low back pain comprising orally administering zoledronic acid to a human being in need thereof, wherein the amount of zoledronic acid orally administered to the human being within a period of about one month is about 400 mg to about 500 mg.
2. The method of claim 1 , wherein the zoledronic acid is in an acid form.
3. The method of claim 1 , wherein the zoledronic acid is in a salt form.
4. The method of claim 3 , wherein the imidazole ring of zoledronic acid is in an imidazolium form.
5. The method of claim 1 , wherein the zoledronic acid is orally administered in at least two consecutive doses that are at least about 1 week apart.
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 AUC of zoledronic acid in the human being, measured over a period of one month, is about 500 ng·h/mL to about 700 ng·h/mL.
9. The method of claim 1 , wherein the AUC of zoledronic acid in the human being, measured over a period of one month, is about 700 ng·h/mL to about 1000 ng·h/mL.
10. The method of claim 1 , wherein the zoledronic acid is in a dosage form that provides a bioavailability of zoledronic acid, when orally administered to the human being in a fasted state, of about 1.1% to about 1.5%.
11. A method of treating chronic low back pain comprising orally administering a dosage form to a human being in need thereof;
wherein the dosage form is prepared by a method comprising combining 1) zoledronic acid with 2) an excipient, a disintegrating agent, a diluent, a binder, a lubricant, a sweetening agent, a flavoring agent, a coating, a capsule, or a combination thereof;
wherein the dosage form is orally administered 2, 3, 4, 5, 6, 7, 8, 9, or 10 times at a frequency that is no greater than about once weekly;
wherein the dosage form contains about 150 mg to about 200 mq of the zoledronic acid, based on the weight of the diacid form; and
wherein no more than 500 mg of the zoledronic acid is orally administered within a period of six months.
12. The method of claim 11 , wherein the zoledronic acid is in an acid form.
13. The method of claim 11 , wherein the zoledronic acid is in a disodium salt form.
14. The method of claim 11 , wherein the imidazole ring of zoledronic acid is in an imidazolium form.
15. The method of claim 11 , wherein the bioavailability of zoledronic acid in the dosage form is about 1% to about 1.3%, as determined when orally administered to a human being who has fasted for eight hours.
16. The method of claim 11 , wherein the bioavailability of zoledronic acid in the dosage form is about 1.2% to about 1.5%, as determined when orally administered to a human being who has fasted for eight hours.
17. The method of claim 11 , wherein the bioavailability of zoledronic acid in the dosage form is about 1.5% to about 2%, as determined when orally administered to a human being who has fasted for eight hours.
18. The method of claim 11 , wherein the bioavailability of zoledronic acid in the dosage form is about 2.5% to about 3%, as determined when orally administered to a human being who has fasted for eight hours.
19. A method of treating chronic low back pain comprising orally administering a dosage form to a human being in need thereof;
wherein the dosage form is prepared by a method comprising combining 1) zoledronic acid with 2) an excipient, a disintegrating agent, a diluent, a binder, a lubricant, a sweetening agent, a flavoring agent, a coating, a capsule, or a combination thereof;
wherein the dosage form is orally administered 2, 3, 4, 5, 6, 7, 8, 9, or 10 times at a frequency that is no greater than about once weekly;
wherein the dosage form contains about 50 mg to about 60 mg of the disodium salt form of zoledronic acid; and
wherein no more than 500 mg of the zoledronic acid is orally administered within a period of six months.
20. The method of claim 11 , wherein the dosage form is orally administered once weekly for 6 weeks.
21. The method of claim 20 , wherein the dosage form contains about 50 mg of zoledronic acid, based on the weight of the diacid form.
22. The method of claim 19 , the human being has an average weekly pain intensity of at least 3, on the 0-10 numeric rating scale, prior to receiving the zoledronic acid.
23. The method of claim 19 , wherein the human being is at least 40 years of age.
24. The method of claim 20 , wherein the bioavailability of zoledronic acid in the dosage form is about 1.8% to about 2.5%, as determined when orally administered to a human being who has fasted for eight hours.
25. The method of claim 24 , wherein a single oral administration of the dosage form to the human being results in an AUC for zoledronic acid of about 130 ng·h/mL to about 160 ng·h/mL.
26. The method of claim 25 , wherein the dosage form is orally administered three times within a period of six months.
27. The method of claim 24 , wherein the dosage form is orally administered six times within a period of six months.
28. The method of claim 24 , wherein, at the beginning of treatment, the human being has an average weekly pain intensity of at least 4 on the 0-10 numeric rating scale.
29. The method of claim 24 , wherein the low back pain is associated with a Modic change.
30. The method of claim 24 , wherein the human being has suffered from low back pain for at least 3 months.