Methods useful for vitamin D deficiency and related disorders
Methods for diagnosing, treating, and preventing catabolism-related vitamin D deficiency and related disorders, related compositions, apparatus and kits, are disclosed. A method involves measuring CYP24 expression and/or activity, or a proxy thereof such as FGF23 level, in a patient and correlating abnormally elevated CYP24 expression and/or activity with catabolism-related vitamin D deficiency or with susceptibility for catabolism-related vitamin D deficiency. In response to abnormally elevated CYP24 expression and/or activity, the method further includes administering a CYP24 inhibitor to the vitamin D deficient or at-risk patient, and preferably avoiding activation of the vitamin D binding receptor, such as by avoiding administration of active vitamin D compounds to such patients. Optionally, a vitamin D prohormone or prohormone can be administered.
1. An extended release pharmaceutical formulation comprising a CYP24 inhibitor and a vitamin D prohormone.
2. The formulation of claim 1 , wherein the CYP24 inhibitor is a pure inhibitor of CYP24 or a dual-action CYP24 inhibitor/VDR agonist.
3. The formulation of claim 1 , wherein the CYP24 inhibitor is selected from 23,23-difluoro-24-sulfone vitamin D 3 compounds, 25-sulfone vitamin D 3 compounds, 24,24-difluoro-25-sulfone vitamin D 3 compounds, 24-sulfoximine vitamin D 3 compounds, 16-ene-25-oxime vitamin D 3 compounds, and 16-ene-25-oxime ether vitamin D 3 compounds, 24-sulfone vitamin D 3 compounds, and 24,24-difluoro vitamin D 3 compounds.
4. The formulation of claim 1 , wherein the vitamin D prohormone is selected from 25-hydroxyvitamin D 2 , 25-hydroxyvitamin D 3 , and combinations thereof.
5. The formulation of claim 4 , wherein the vitamin D prohormone is 25-hydroxyvitamin D 3 .
6. The formulation of claim 1 , wherein the formulation is for oral administration.
7. The formulation of claim 1 , further comprising an oil.
8. The formulation of claim 7 , further comprising esters of fatty acids.
9. The formulation of claim 8 , wherein the esters of fatty acids are fatty acid glycerides.
10. The formulation of claim 1 , wherein the formulation comprises a capsule.
11. A method of treating vitamin D deficiency in a patient comprising administering to the patient an effective amount of the formulation of claim 1 to increase to or maintain serum 25-hydroxyvitamin D at a level of at least 30 ng/m L.
12. The method of claim 11 , wherein the CYP24 inhibitor is a pure inhibitor of CYP24 or a dual-action CYP24 inhibitor/VDR agonist.
13. The method of claim 11 , wherein the CYP24 inhibitor is selected from 23,23-difluoro-24-sulfone vitamin D 3 compounds, 25-sulfone vitamin D 3 compounds, 24,24-difluoro-25-sulfone vitamin D 3 compounds, 24-sulfoximine vitamin D 3 compounds, 16-ene-25-oxime vitamin D 3 compounds, and 16-ene-25-oxime ether vitamin D 3 compounds, 24-sulfone vitamin D 3 compounds, and 24,24-difluoro vitamin D 3 compounds.
14. The method of claim 11 , wherein the vitamin D prohormone is selected from 25-hydroxyvitamin D 2 , 25-hydroxyvitamin D 3 , and combinations thereof.
15. The method of claim 14 , wherein the vitamin D prohormone is 25-hydroxyvitamin D 3 .
16. The method of claim 11 , wherein the extended release formulation is administered orally.
17. The method of claim 11 , wherein the extended release formulation comprises an oil.
18. The method of claim 17 , wherein the extended release formulation comprises esters of fatty acids.
19. The method of claim 18 , wherein the esters of fatty acids are fatty acid glycerides.
20. The method of claim 11 , wherein the extended release formulation comprises a capsule.
21. The method of claim 11 , wherein the patient has secondary hyperparathyroidism.
22. The method of claim 11 , wherein the patient has Chronic Kidney Disease Stage 1 or Stage 2.
23. The method of claim 11 , wherein the patient has Chronic Kidney Disease Stage 3 or Stage 4.
24. The method of claim 11 , wherein the patient has Chronic Kidney Disease Stage 5.
25. A method of treating secondary hyperparathyroidism in a patient having Chronic Kidney Disease (CKD) comprising administering an effective amount of the formulation of claim 1 to lower serum parathyroid hormone.
26. The method of claim 25 , wherein the CYP24 inhibitor is a pure inhibitor of CYP24 or a dual-action CYP24 inhibitor/VDR agonist.
27. The method of claim 25 , wherein the CYP24 inhibitor is selected from 23,23-difluoro-24-sulfone vitamin D 3 compounds, 25-sulfone vitamin D 3 compounds, 24,24-difluoro-25-sulfone vitamin D 3 compounds, 24-sulfoximine vitamin D 3 compounds, 16-ene-25-oxime vitamin D 3 compounds, and 16-ene-25-oxime ether vitamin D 3 compounds, 24-sulfone vitamin D 3 compounds, and 24,24-difluoro vitamin D 3 compounds.
28. The method of claim 25 , wherein the vitamin D prohormone is selected from 25-hydroxyvitamin D 2 , 25-hydroxyvitamin D 3 , and combinations thereof.
29. The method of claim 28 , wherein the vitamin D prohormone is 25-hydroxyvitamin D 3 .
30. The method of claim 25 , wherein the extended release formulation is administered orally.
31. The method of claim 25 , wherein the extended release formulation comprises an oil.
32. The method of claim 31 , wherein the extended release formulation comprises esters of fatty acids.
33. The formulation of claim 32 , wherein the esters of fatty acids are fatty acid glycerides.
34. The method of claim 25 , wherein the extended release formulation comprises a capsule.
35. The method of claim 25 , wherein the patient has Chronic Kidney Disease Stage 1 or Stage 2.
36. The method of claim 25 , wherein the patient has Chronic Kidney Disease Stage 3 or Stage 4.
37. The method of claim 25 , wherein the patient has Chronic Kidney Disease Stage 5.