COMPOSITIONS FOR ORAL ADMINISTRATION OF ZOLEDRONIC ACID OR RELATED COMPOUNDS FOR TREATING MUSCULOSKELETAL PAIN
Oral dosage forms of bisphosphonate compounds, such as zoledronic acid, can be used to treat or alleviate pain or related conditions. The oral bioavailabilty of zoledronic acid can be enhanced by administering the zoledronic acid in the disodium salt form
1 . A method of treating musculoskeletal pain, comprising orally administering zoledronic acid to a mammal in need thereof, wherein the zoledronic acid 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 is administered once a month, or less frequently.
3 . The method of claim 2 , wherein the mammal experiences pain relief at least 3 weeks after a dose of zoledronic acid is administered.
4 . The method of claim 1 , wherein the zoledronic acid is administered weekly.
5 . The method of claim 4 , wherein the mammal experiences pain relief at least 48 hours after a dose of zoledronic acid is administered.
6 . The method of claim 1 , wherein the zoledronic acid is administered 2 to 5 times in a month.
7 . The method of claim 6 wherein the mammal experiences pain relief at least 12 hours after a dose of zoledronic acid is administered.
8 . The method of claim 1 , wherein the zoledronic acid is administered daily.
9 . The method of claim 8 wherein the mammal experiences pain relief at least 12 hours after a dose of zoledronic acid is administered.
10 . The method of claim 1 , wherein the mammal is a human being.
11 . The method of claim 10 , wherein the human being to which the zoledronic acid is administered does not eat food or drink beverage for at least 1 hour before the zoledronic acid is administered.
12 . The method of claim 1 , wherein the zoledronic acid is administered orally in a dosage form that is substantially free of bioavailability-enhancing agents, and wherein the dosage form has a bioavailability of 1.5% to 3% in the mammal being treated.
13 . The method of claim 1 , wherein the zoledronic acid is administered in a solid dosage form having a hardness of at least about 5 kPa.
14 . A method of treating musculoskeletal pain, comprising orally administering zoledronic acid to a mammal in need thereof, wherein the zoledronic acid 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 the zoledronic acid is administered.
15 . The method of claim 14 , wherein the zoledronic acid is administered weekly.
16 . The method of claim 14 , wherein the mammal experiences pain relief at least 24 hours after a dose of zoledronic acid is administered.
17 . The method of claim 14 , wherein the mammal is a human being.
18 . The method of claim 17 , wherein human being to which the zoledronic acid is administered does not eat food or drink beverage for at least 2 hours before the zoledronic acid is administered.
19 . The method of claim 14 , wherein the zoledronic acid is administered in a solid dosage form that contains at least about 50% (w/w) of zoledronic acid.
20 . The method of claim 14 , wherein the zoledronic acid is administered in a solid dosage form having a hardness of about 5 kPa to about 20 kPa.
21 . A method of treating musculoskeletal pain, comprising orally administering zoledronic acid to a mammal in need thereof, wherein the zoledronic acid is administered daily, and a daily dose contains an amount of zoledronic acid that results in an AUC of zoledronic acid that is about 4 ng·h/mL to about 30 ng·h/mL.
22 . The method of claim 21 , wherein the mammal is a human being.
23 . The method of claim 22 , wherein human being to which the zoledronic acid is administered does not eat food or drink beverage for at least 2 hours before the zoledronic acid is administered.
24 . The method of claim 21 , wherein the zoledronic acid is administered orally in a dosage form that has a bioavailability of 1.5% to 3% in the mammal being treated.
25 . A method of relieving musculoskeletal pain, comprising administering an oral dosage form containing zoledronic acid to a mammal in need thereof, wherein the mammal receives a total monthly dose of zoledronic acid that is about 800 mg/m 2 or less based upon the body surface area of the mammal.
26 . The method of claim 25 , wherein the zoledronic acid is administered orally in a dosage form that has a bioavailability of 1.5% to 3% in the mammal.
27 . The method of claim 26 , wherein the mammal receives a total monthly dose of zoledronic acid that is about 30 mg/m 2 to about 700 mg/m 2 based upon the body surface area of the mammal.
28 . The method of claim 25 , wherein the mammal is a human being who does not eat food or drink beverage for at least 30 minutes after the zoledronic acid is administered.
29 . The method of claim 25 , wherein zoledronic acid is administered for only 1 to 3 months.