Compositions for oral administration of zoledronic acid or related compounds for treating disease
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 enhancing the oral bioavailability of zoledronic acid comprising orally administering a dosage form containing zoledronic acid in the disodium salt form to a mammal in need of treatment by zoledronic acid.
2. The method of claim 1 , wherein the zoledronic acid in the disodium salt form provides an enhancement to bioavailability, as compared to zoledronic acid in the diacid form, which adds to any enhancement to bioavailability provided by any bioavailability-enhancing agents in the dosage form.
3. The method of claim 1 , wherein the zoledronic acid in the disodium salt form is administered to a mammal in an amount that provides an area under the plasma concentration curve of zoledronic acid of about 4 ng·h/mL to about 2000 ng·h/mL to the mammal each time the zoledronic acid in the disodium salt form is administered.
4. The method of claim 3 , wherein the zoledronic acid in the disodium salt form is administered at an interval of about 3 to about 4 weeks in an amount that provides an area under the plasma concentration curve of zoledronic acid of about 100 ng·h/mL to about 2000 ng·h/mL to the mammal each time the zoledronic acid in the disodium salt form is administered.
5. The method of claim 3 , wherein the zoledronic acid in the disodium salt form is administered weekly, or 3 to 5 times in a month, in an amount that provides an area under the plasma concentration curve of zoledronic acid of about 20 ng·h/mL to about 700 ng·h/mL to the mammal each time the zoledronic acid in the disodium salt form is administered.
6. The method of claim 3 , wherein the zoledronic acid in the disodium salt form is administered daily in an amount that provides an area under the plasma concentration curve of zoledronic acid of about 4 ng·h/mL to about 100 ng·h/mL to the mammal each time the zoledronic acid in the disodium salt form is administered.
7. The method of claim 1 , wherein the dosage form is a solid.
8. The method of claim 1 , wherein the bioavailability of zoledronic acid is improved by at least about 20% as compared to administration of zoledronic acid in the diacid form.
9. The method of claim 1 , further comprising administering, on a molar basis, less of the zoledronic acid in the disodium salt form than would be administered of zoledronic acid in the diacid form in order to achieve the same plasma levels of zoledronic acid.
10. The method of claim 9 , wherein at least about 10 mole % less of the disodium salt form is administered as compared to the amount of zoledronic acid in the diacid form that would be administered in order to achieve the same plasma levels of zoledronic acid.
11. The method of claim 9 , wherein the disodium salt form is administered in an amount, on a molar basis, that has a value of about 0.8n d to about 1.2n d , wherein:
n d =( b a /b d )( n a )
wherein b a is the bioavailability of the diacid form, b d is the bioavailability of the disodium salt form, and n a is the number of moles of zoledronic acid in the diacid form that would be administered in order to achieve the same plasma levels of zoledronic acid.
12. The method of claim 1 , wherein the zoledronic acid is used to treat an inflammatory condition.
13. The method of claim 1 , wherein the zoledronic acid is used to treat arthritis or complex regional pain syndrome.
14. The method of claim 1 , wherein the zoledronic acid is for the treatment of an inflammatory condition, arthritis, or complex regional pain syndrome, and wherein:
a first oral dosage form is administered; and
a second oral dosage form is administered;
wherein, with respect to the first oral dosage form, the second oral dosage form is administered at 10×T max or greater, wherein T max is the time of maximum plasma concentration for the first oral dosage form.
15. The method of claim 1 , wherein the zoledronic acid is for the treatment of an inflammatory condition, arthritis, or complex regional pain syndrome, and wherein:
only a single oral dosage form is administered; or
a first oral dosage form is administered, and a second oral dosage form is administered about 24 hours to about 60 days after the first oral dosage form.
16. The method of claim 15 , wherein the second oral dosage form is administered about 24 hours to about 28 days after the first oral dosage form is administered.