Methods 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 increasing blood 1,25-dihydroxyvitamin D level in a human patient, comprising administering to the patient an effective amount of a controlled release, oral-dosage form comprising 25-hydroxyvitamin D to raise or maintain the patient's blood 1,25-dihydroxyvitamin D level to at least about 25 pg/mL without causing hypercalcemia, wherein the patient has a vitamin D-responsive disease selected from parathyroid disorders, bone disorders, cardiovascular diseases, and combinations thereof, and the 25-hydroxyvitamin D is administered in an amount of 1 to 1000 μg per unit dose.
2. The method of claim 1 , wherein the 25-hydroxyvitamin D comprises 25-hydroxyvitamin D 3 , 25-hydroxyvitamin D 2 , or a combination thereof.
3. The method of claim 1 , wherein the 25-hydroxyvitamin D comprises 25-hydroxyvitamin D 3 .
4. The method of claim 1 , wherein the 25-hydroxyvitamin D consists of 25-hydroxyvitamin D 3 .
5. The method of claim 1 , wherein said administration maintains blood 1,25-dihydroxyvitamin D level above 25 pg/mL.
6. The method of claim 1 , wherein said administration raises or maintains blood 1,25-dihydroxyvitamin D level to at least 30 pg/mL.
7. The method of claim 1 , wherein said administration raises or maintains blood 1,25-dihydroxyvitamin D level to a concentration in a range of about 25 pg/mL to about 65 pg/mL.
8. The method of claim 1 , wherein the effective amount of said controlled release, oral dosage form of 25-hydroxyvitamin D does not increase total serum or blood level of 1,25-dihydroxyvitamin D by greater than 75 pg/mL after administration of said dose.
9. The method of claim 1 , wherein said administration is continued to maintain said increased blood level of 1,25-dihydroxyvitamin D for at least one month.
10. The method of claim 9 , wherein said administration is continued to maintain said increased blood level of 1,25-dihydroxyvitamin D for at least three months.
11. The method of claim 10 , wherein said administration is continued to maintain said increased blood level of 1,25-dihydroxyvitamin D for at least six months.
12. The method of claim 1 , wherein the patient is vitamin D insufficient or deficient.
13. The method of claim 1 , wherein the patient is vitamin D replete.
14. The method of claim 1 , wherein the patient has a disease selected from the group consisting of hyperparathyroidism, secondary hyperparathyroidism, and combinations thereof.
15. A method of increasing blood 1,25-dihydroxyvitamin D level in a human patient, comprising administering to the patient an effective amount of a controlled release, oral dosage form comprising 25-hydroxyvitamin D 3 to increase or maintain blood 1,25-dihydroxyvitamin D level in a range of about 25 pg/mL to about 65 pg/mL and continuing said administering to maintain said increased blood 1,25-dihydroxyvitamin D level for at least one month without causing hypercalcemia, wherein the patient has vitamin D-responsive disease selected from parathyroid disorders, bone disorders, cardiovascular diseases, and combinations thereof and wherein the 25-hydroxyvitamin D 3 is administered in an amount of 1 to 1000 μg per unit dose.
16. A method of increasing blood 1,25-dihydroxyvitamin D level in a human patient, comprising administering to the patient an effective amount of a controlled release, oral dosage form consisting of 25-hydroxyvitamin D 3 to increase or maintain blood 1,25-dihydroxyvitamin D level to at least about 25 pg/mL without causing hypercalcemia wherein the effective amount of said controlled release, oral dosage form of 25-hydroxyvitamin D does not increase total serum or blood level of 1,25-dihydroxyvitamin D by greater than 75 pg/mL after administration of said dose, wherein the patient has a vitamin D-responsive disease selected from parathyroid disorders, bone disorders, cardiovascular diseases, and combinations thereof and wherein the 25-hydroxyvitamin D 3 is administered in an amount of 1 to 1000 μg per unit dose.
17. A method of increasing blood 1,25-dihydroxyvitamin D level in a human patient, comprising administering to the patient an effective amount of a controlled release, oral dosage form comprising 25-hydroxyvitamin D to raise or maintain blood 1,25-dihydroxyvitamin D level to at least about 25 pg/mL without causing substantially increased catabolism of the administered 25-hydroxyvitamin D or hypercalcemia, wherein the patient has a vitamin D-responsive disease selected from parathyroid disorders, bone disorders, cardiovascular diseases, and combinations thereof and wherein the 25-hydroxyvitamin D 3 is administered in an amount of 1 to 1000 μg per unit dose.