Methods and compositions for reducing parathyroid levels
Methods and compositions for reducing serum parathyroid levels in, for example, chronic kidney disease patients are disclosed. In these methods, an effective amount of a modified release formulation of 25-hydroxyvitamin D is orally administered to a patient suffering from secondary hyperparathyroidism to lower the patient's serum intact parathyroid hormone (iPTH) level, while avoiding a surge in serum total 25-hydroxyvitamin D.
1 . A method of treating secondary hyperparathyroidism, comprising orally administering to a human patient suffering from secondary hyperparathyroidism an effective amount of a modified release dosage form comprising 25-hydroxyvitamin D 2 , 25-hydroxyvitamin D 3 , or a combination thereof, to provide a rise in serum total 25-hydroxyvitamin D of at least 7 ng/ml and no greater than 30 ng/ml within the first 24 hours after said administering and lower the patient's serum intact parathyroid hormone (iPTH) level by at least 10% compared to baseline within 24 hours after said administering.
2 . The method according to claim 1 , wherein the amount of said modified release dosage form administered is effective to provide a rise in serum total 25-hydroxyvitamin D of at least 8 ng/ml and no greater than 16 ng/ml within the first 24 hours after dosing.
3 . The method according to claim 2 , wherein the amount of said modified release dosage form administered is effective to provide a rise in serum total 25-hydroxyvitamin D of at least 10 ng/ml and no greater than 14 ng/ml within the first 24 hours after dosing.
4 . The method of claim 1 , wherein the patient's serum total 25-hydroxyvitamin D is raised to at least 30 ng/ml.
5 . The method of claim 1 , wherein the patient's iPTH level is lowered by at least 15% compared to baseline.
6 . The method of claim 1 , wherein the patient's iPTH level remains lowered for at least 48 hours.
7 . The method of claim 6 , wherein the patient's iPTH level remains lowered for at least 7 days.
8 . The method of claim 1 , wherein said method of treatment further comprises performing said administering step on a frequency of every other day, or less.
9 . The method of claim 8 , wherein said frequency is weekly.
10 . The method of claim 9 , wherein said frequency is monthly.
11 . The method of claim 1 , wherein the bioavailable amount of the 25-hydroxyvitamin D 2 , 25-hydroxyvitamin D 3 , or combination thereof administered is greater than 45 μg.
12 . The method of claim 11 , wherein the bioavailable amount of the 25-hydroxyvitamin D 2 , 25-hydroxyvitamin D 3 , or combination thereof administered is in a range of 70 to 110 μg.
13 . The method of claim 1 , wherein the patient suffers from hyperparathyroidism secondary to chronic kidney disease (CKD).
14 . The method of claim 13 , wherein said CKD is Stage 2, Stage 3, Stage 4, or Stage 5 CKD.
15 . The method of claim 14 , wherein said CKD is Stage 3 or Stage 4.
16 . The method of claim 1 , wherein the amount of said modified release dosage form administered is further effective to provide a rise in serum total 1,25-dihydroxyvitamin D of greater than 3 pg/ml and less than 10 pg/ml within the first 24 hours after dosing.
17 . The method of claim 16 , wherein the rise in serum total 1,25-dihydroxyvitamin D is at least 7 pg/ml and less than 10 pg/ml within the first 48 hours after dosing.
18 . The method of claim 1 , wherein the T max of serum total 25-hydroxyvitamin D following said administering step is at least 4 hours.
19 . The method of claim 18 , wherein the T max of serum total 25-hydroxyvitamin D following said administering step is at least 12 hours.
20 . The method of claim 1 , wherein the patient also suffers from vitamin D insufficiency or deficiency, as defined by serum total 25-hydroxyvitamin D of less than 30 ng/ml.
21 . The method of claim 1 , wherein the modified release dosage form comprises 25-hydroxyvitamin D 3 .