Method for controlled release oral dosage of a vitamin D compound
A stable, controlled release formulation for oral dosing of vitamin D compounds is disclosed. The formulation is prepared by incorporating one or more vitamin D compounds into a solid or semi-solid mixture of waxy materials. Oral dosage forms can be prepared by melt-blending the components described herein and filling gelatin capsules with the formulation.
1. A method of treating secondary hyperparathyroidism in a human patient having Chronic Kidney Disease (CKD), comprising administering to the human patient having CKD an effective amount of a sustained release, oral dosage form of 25-hydroxyvitamin D to treat the secondary hyperparathyroidism and reduce the patient's serum parathyroid hormone level, wherein the administration avoids transient increases in blood levels of 25-hydroxyvitamin D of greater than 3 ng/mL following a unit dose.
2. The method of claim 1 , comprising administering 30 μg or 60 μg of 25-hydroxyvitamin D 3 .
3. The method of claim 1 , wherein the sustained release, oral dosage form of 25-hydroxyvitamin D comprises a waxy controlled release carrier.
4. The method of claim 3 , wherein the sustained release, oral dosage form of 25-hydroxyvitamin D comprises a waxy controlled release carrier, a lipoidic agent, and an oily vehicle for the 25-hydroxyvitamin D compound.
5. The method of claim 1 , comprising administering said oral dosage on a schedule of once per day.
6. The method of claim 1 , wherein the patient has CKD Stage 5.
7. The method of claim 1 , wherein the patient has CKD Stage 1 or 2.
8. The method of claim 1 , wherein the patient has CKD Stage 3 or 4.
9. A method of treating secondary hyperparathyroidism in a human patient having Chronic Kidney Disease (CKD), comprising administering to the human patient having CKD an effective amount of a sustained release, oral dosage form of 25-hydroxyvitamin D to treat the secondary hyperparathyroidism and reduce the patient's serum parathyroid hormone level, wherein the sustained release is effected over a period of at least four hours.
10. The method of claim 9 , comprising administering 30 μg or 60 μg of 25-hydroxyvitamin D 3 .
11. The method of claim 9 , wherein the administration avoids transient increases in blood levels of 25-hydroxyvitamin D of greater than 3 ng/mL following a unit dose.
12. The method of claim 9 , wherein the sustained release, oral dosage form of 25-hydroxyvitamin D comprises a waxy controlled release carrier.
13. The method of claim 9 , comprising administering said oral dosage on a schedule of once per day.
14. The method of claim 9 , wherein the patient has CKD Stage 5.
15. The method of claim 9 , wherein the patient has CKD Stage 1 or 2.
16. The method of claim 9 , wherein the patient has CKD Stage 3 or 4.
17. A method of treating secondary hyperparathyroidism in a human patient having Chronic Kidney Disease (CKD), comprising administering to the human patient having CKD an effective amount of a sustained release, oral dosage form of 25-hydroxyvitamin D to treat the secondary hyperparathyroidism and reduce the patient's serum parathyroid hormone level, such that (a) the ratio of the maximum serum concentration within 24 hours after administration of the vitamin D compound to the concentration 24 hours after administration (Cmax 24hr /C 24hr ) is reduced as compared to an equivalent amount of the vitamin D compound administered by an immediate-release, oral dosage form and/or
(b) the time for the plasma concentration of the vitamin D compound to reach its maximum in a dose interval following administration (Tmax) is increased as compared to Tmax for an equivalent amount of the vitamin D compound administered by an equivalent immediate-release, oral dosage form, wherein the vitamin D compound comprises 25-hydroxyvitamin D 3 .
18. The method of claim 17 , comprising administering 30 μg or 60 μg of 25-hydroxyvitamin D 3 .
19. The method of claim 17 , wherein the administration avoids transient increases in blood levels of 25-hydroxyvitamin D of greater than 3 ng/mL following a unit dose.
20. The method of claim 17 , wherein the sustained release, oral dosage form of 25-hydroxyvitamin D comprises a waxy controlled release carrier.
21. The method of claim 17 , comprising administering said oral dosage on a schedule of once per day.
22. The method of claim 17 , wherein the patient has CKD Stage 5.
23. The method of claim 17 , wherein the patient has CKD Stage 1 or 2.
24. The method of claim 17 , wherein the patient has CKD Stage 3 or 4.
25. A method of treating a disease or condition, comprising administering to a human patient 30 μg or 60 μg of an extended release, oral dosage form of 25-hydroxyvitamin D 3 once daily, wherein the disease or condition is secondary hyperparathyroidism in an adult human patient having Chronic Kidney Disease (CKD) Stage 3 or 4 and serum total 25-hydroxyvitamin D levels less than 30 ng/mL.
26. The method of claim 25 , wherein the sustained release, oral dosage form of 25-hydroxyvitamin D comprises a waxy controlled release carrier.
27. The method of claim 26 , wherein the sustained release, oral dosage form of 25-hydroxyvitamin D comprises a waxy controlled release carrier, a lipoidic agent, and an oily vehicle for the 25-hydroxyvitamin D compound.
28. The method of claim 25 , wherein the patient has CKD Stage 5.
29. The method of claim 25 , wherein the patient has CKD Stage 1 or 2.
30. The method of claim 25 , wherein the patient has CKD Stage 3 or 4.