Method of treating and preventing secondary hyperparathyroidism
The method of treating elevated blood levels of iPTH by increasing or maintaining blood concentrations of both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in a patient by administering, as necessary, both Vitamin D repletion and Vitamin D hormone replacement therapies, is disclosed. The blood concentrations of 25-hydroxyvitamin D are increased to and maintained at or above 30 ng/mL, and blood concentrations of 1,25-dihydroxyvitamin D are increased to or maintained within a patient's normal historical physiological range for 1,25-dihydroxyvitamin D without causing substantially increased risk of hypercalcemia, hyperphosphatemia or over suppression of plasma iPTH in the patient. The blood levels of 25-hydroxyvitamin D are maintained at or above 30 ng/mL between doses of Vitamin D repletion therapies, and the blood levels of 1,25-dihydroxyvitamin D are maintained in the patient's normal historical physiological range between doses of Vitamin D hormone replacement therapies. In one aspect, the disclosure includes methods wherein the blood concentration of 25-hydroxyvitamin D during treatment comprises predominantly 25-hydroxyvitamin D 3 , and/or wherein the method includes administering predominantly or solely 25-hydroxyvitamin D 3 for 25-hydroxyvitamin D repletion and/or maintenance.
1. A pharmaceutical dosage form, comprising a combination of
(a) a 25-hydroxyvitamin D compound and;
(b) an active Vitamin D hormone;
wherein the dosage form is oral and is formulated for controlled release of the 25-hydroxyvitamin D compound, the active Vitamin D hormone, or both the 25-hydroxyvitamin D compound and the active Vitamin D hormone, wherein the active Vitamin D hormone is selected from one or more 1α-hydroxylated Vitamin D compounds.
2. The pharmaceutical dosage form of claim 1 , wherein the 25-hydroxyvitamin D compound comprises 25-hydroxyvitamin D 3 .
3. The pharmaceutical dosage form of claim 2 , wherein the 25-hydroxyvitamin D compound comprises predominantly 25-hydroxyvitamin D 3 .
4. The pharmaceutical dosage form of claim 1 , wherein the active Vitamin D hormone comprises one or more of 1,25-dihydroxyvitamin D 2 , 1,25-dihydroxyvitamin D 3 , and 1,25-dihydroxyvitamin D 4 .
5. The pharmaceutical dosage form of claim 4 , wherein the active Vitamin D hormone comprises 1,25-dihydroxyvitamin D 3 .
6. The pharmaceutical dosage form of claim 1 , wherein the dosage form is formulated for controlled release of both the 25-hydroxyvitamin D compound and the active Vitamin D hormone.
7. The pharmaceutical dosage form of claim 1 , further comprising another therapeutically active substance.
8. The pharmaceutical dosage form of claim 1 , further comprising a phosphate binder, a calcimimetic agent, or both a phosphate binder and a calcimimetic agent.
9. The pharmaceutical dosage form of claim 1 , further comprising one or more auxiliary agents selected from a lubricant, preservative, stabilizer, wetting agent, emulsifier, salt for osmotic pressure control, buffer, coloring agent, flavoring agent, and an aromatic active compound.
10. The pharmaceutical dosage form of claim 1 , further comprising a pharmaceutically acceptable carrier.
11. The pharmaceutical dosage form of claim 10 , wherein the dosage form is a tablet, capsule, powder, suppository, or lozenge.
12. The pharmaceutical dosage form of claim 1 , wherein the dosage form is a tablet, dragée, liquid, drop, lozenge, powder, or capsule.
13. The pharmaceutical dosage form of claim 1 , wherein the formulation comprises a liposome, a microencapsulate, multiple coatings, differentially degradable coatings, or a combination thereof.
14. The pharmaceutical dosage form of claim 1 , wherein the dosage form is formulated for sustained release of the 25-hydroxyvitamin D compound, the active Vitamin D hormone, or both the 25-hydroxyvitamin D compound and the active Vitamin D hormone.
15. The pharmaceutical dosage form of claim 14 , wherein the formulation comprises a liposome, a microencapsulate, multiple coatings, differentially degradable coatings, or a combination thereof.
16. The pharmaceutical dosage form of claim 1 , wherein the 25-hydroxyviatmin D is present in an amount in a range of 1 μg to 1000 μg.
17. The pharmaceutical dosage form of claim 1 , wherein the active Vitamin D hormone is present in an amount in a range of 0.1 μg to 10 μg.
18. A pharmaceutical dosage form, comprising a combination of
(a) 25-hydroxyvitamin D 3 compound present in an amount in a range of 1 μg to 1000 μg and;
(b) 1,25-dihydroxyvitamin D 3 present in an amount in a range of 0.1 μg to 10 μg; wherein the dosage form comprises a pharmaceutically acceptable carrier is formulated as an oral dosage form for sustained release.
19. A kit for treatment of a patient diagnosed with secondary hyperparathyroidism, comprising a member selected from the group consisting of a 25-hydroxyvitamin D compound, an active Vitamin D hormone, and combinations thereof, and written instructions for co-treatment of said patient with a 25-hydroxyvitamin D compound and an active Vitamin D hormone, wherein the active Vitamin D hormone is selected from one or more 1α-hydroxylated Vitamin D compounds.
20. The kit of claim 19 , comprising an oral, sustained release dosage form comprising a 25-hydroxyvitamin D compound and a transdermal formulation comprising an active vitamin D compound.