Osteoclast Inhibitors for Knee Conditions
Oral dosage forms of bisphosphonate compounds, such as zoledronic acid, can be used to treat or alleviate pain or related conditions such as arthritis.
1 . A method of treating pain associated with arthritis 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 in a fasted state, of about 1.1% to about 1.5%.
11 . A method of treating pain associated with arthritis 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) about 30 mg to about 200 mg of 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; and
no more than 500 mg of 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 . The method of claim 11 , wherein the dosage form contains about 150 mg to about 200 mg of zoledronic acid, based on the weight of the diacid form.
20 . The method of claim 11 , wherein the dosage form contains about 50 mg to about 60 mg of the disodium salt form of zoledronic acid.
21 . The method of claim 11 , wherein the dosage form contains about 50 mg of zoledronic acid, based on the weight of the diacid form.
22 . The method of claim 11 , the human being has an average weekly pain intensity of at least 3, on the 0-10 numeric rating scale, prior to receiving zoledronic acid.
23 . The method of claim 11 , wherein the human being is at least 40 years of age.
24 . A method of treating pain associated with arthritis comprising orally administering a dosage form comprising zoledronic acid in an acid or a salt form to a human being in need thereof, 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 results in an AUC for zoledronic acid of about 130 ng·hr/mL to about 160 ng·hr/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 arthritis is associated with a bone marrow lesion.
30 . The method of claim 24 , wherein the human being has OARSI Grade 0 joint space narrowing.