TREATING DISEASE USING COMPOSITIONS FOR ORAL ADMINISTRATION OF ZOLEDRONIC ACID OR RELATED COMPOUNDS
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 a disease or condition related to bone, cancer, or pain, comprising administering an oral dosage form comprising zoledronic acid to a mammal in need thereof, wherein the zoledronic acid is present in the oral dosage form in an amount that results in an AUC of zoledronic acid of about 50 ng·hr/mL to about 700 ng·hr/mL upon administration of the oral dosage form to the mammal.
2 . The method of claim 1 , wherein the zoledronic acid is present in an amount that results in an AUC of zoledronic acid of about 130 ng·hr/mL to about 180 ng·hr/mL upon administration of the oral dosage form to the mammal.
3 . The method of claim 1 , wherein the zoledronic acid is present in an amount that results in an AUC of zoledronic acid of about 300 ng·hr/mL to about 450 ng·hr/mL upon administration of the oral dosage form to the mammal.
4 . The method of claim 1 , wherein the zoledronic acid is present in an amount that results in an AUC of zoledronic acid of about 300 ng·hr/mL to about 350 ng·hr/mL upon administration of the oral dosage form to the mammal.
5 . The method of claim 1 , wherein the zoledronic acid is present in an amount that results in an AUC of zoledronic acid of about 370 ng·hr/mL to about 420 ng·hr/mL upon administration of the oral dosage form to the mammal.
6 . A method of treating a disease or condition related to bone, cancer, or pain, comprising administering an oral dosage form comprising zoledronic acid to a mammal in need thereof, wherein the zoledronic acid is present in the oral dosage form in an amount that results in a C max of zoledronic acid of about 5 ng/mL to about 300 ng/mL upon administration of the oral dosage form to the mammal.
7 . The method of claim 6 , wherein the zoledronic acid is present in an amount that results in a C max of zoledronic acid of about 5 ng/mL to about 50 ng/mL upon administration of the oral dosage form to the mammal.
8 . The method of claim 6 , wherein the zoledronic acid is present in an amount that results in a C max of zoledronic acid of about 50 ng/mL to about 200 ng/mL upon administration of the oral dosage form to the mammal.
9 . A method of treating a disease or condition related to bone, cancer, or pain, comprising administering an oral dosage form comprising zoledronic acid to a mammal in need thereof, wherein the oral dosage form is configured so that administration of the oral dosage form to the particular species of mammal results in a T max of zoledronic acid of about 0.4 hr to about 1 hr.
10 . The method of claim 9 , wherein the oral dosage form is configured so that administration of the oral dosage form to the mammal results in a T max of zoledronic acid of about 0.5 hr.
11 . The method of claim 9 , wherein the oral dosage form is configured so that administration of the oral dosage form to the mammal results in a T max of zoledronic acid of about 0.75 hr.
12 . A method of treating a disease or condition related to bone, cancer, or pain, comprising administering an oral dosage form comprising zoledronic acid to a mammal in need thereof, wherein the oral dosage form is configured so that the zoledronic acid has a 12 hour sustained plasma level factor of about 12 to about 50 for the mammal.
13 . The method of claim 12 , wherein the oral dosage form is configured so that the zoledronic acid has a 12 hour sustained plasma level factor of about 20 to about 40 for the mammal.
14 . The method of claim 12 , wherein the oral dosage form is configured so that the zoledronic acid has a 24 hour sustained plasma level factor of about 10 to about 30 for the mammal.
15 . The method of claim 14 , wherein the oral dosage form is configured so that the zoledronic acid has a 24 hour sustained plasma level factor of about 10 to about 20 for the mammal.
16 . The method of claim 12 , wherein the oral dosage form is configured so that the zoledronic acid has a 36 hour sustained plasma level factor of about 6 to about 20 for the mammal.
17 . The method of claim 16 , wherein the oral dosage form is configured so that the zoledronic acid has a 36 hour sustained plasma level factor of about 8 to about 15 for the mammal.
18 . The method of claim 12 , wherein the oral dosage form is configured so that the zoledronic acid has a 48 hour sustained plasma level factor of about 5 to about 20 for the mammal.
19 . The method of claim 18 , wherein the oral dosage form is configured so that the zoledronic acid has a 48 hour sustained plasma level factor of about 6 to about 15 for the mammal.
20 . The method of claim 12 , wherein the oral dosage form is configured so that the zoledronic acid has a 72 hour sustained plasma level factor of about 4 to about 20 for the mammal.
21 . The method of claim 20 , wherein the oral dosage form is configured so that the zoledronic acid has a 72 hour sustained plasma level factor of about 5 to about 10 for the mammal.
22 . The method of claim 6 , wherein the oral dosage form is configured so that the particular species of mammal has a plasma concentration of zoledronic acid at 12 hours that is about 0.5 ng/mL to about 5 ng/mL.
23 . The method of claim 22 , wherein the oral dosage form is configured so that the particular species of mammal has a plasma concentration of zoledronic acid at 24 hours that is about 0.2 ng/mL to about 2 ng/mL.
24 . The method of claim 22 , wherein the oral dosage form is configured so that the particular species of mammal has a plasma concentration of zoledronic acid at 36 hours that is about 0.1 ng/mL to about 2 ng/mL.
25 . The method of claim 22 , wherein the oral dosage form is configured so that the particular species of mammal has a plasma concentration of zoledronic acid at 48 hours that is about 0.1 ng/mL to about 2 ng/mL.
26 . The method of claim 22 , wherein the oral dosage form is configured so that the particular species of mammal has a plasma concentration of zoledronic acid at 72 hours that is about 0.2 ng/mL to about 1 ng/mL.
27 . The method of claim 1 , comprising administering an oral dosage form comprising zoledronic acid to a mammal in need thereof, wherein the oral dosage form is configured so that the elimination half-life of zoledronic acid in the particular species of mammal is about 30 hours to about 100 hours.
28 . The method of claim 27 , wherein the oral dosage form is configured so that the elimination half-life of zoledronic acid in the particular species of mammal is about 40 hours to about 60 hours.