Methods and Compounds for Vitamin D Therapy

Abstract

Methods and compositions comprising 1,25-dihydroxyvitamin D 2 are disclosed. A method for lowering or maintaining lowered serum parathyroid hormone in human patients including administering to said patients an effective amount of 1,25-dihydroxyvitamin D 2 to lower or maintain lowered serum parathyroid hormone levels is disclosed. Dosage forms and dosing regimens are also disclosed.

What is claimed is: 
     
         1 . A pharmaceutical composition having serum or plasma intact parathyroid hormone lowering activity, which includes an effective amount of 1,25-dihydroxyvitamin D 2  and at least one pharmaceutically acceptable excipient. 
     
     
         2 . The pharmaceutical composition of  claim 1 , in unit dosage form. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein said at least one pharmaceutically acceptable excipient provides for controlled release of 1,25-dihydroxyvitamin D 2 . 
     
     
         4 . The pharmaceutical composition of  claim 3 , wherein said at least one pharmaceutically acceptable excipient provides for substantially constant release of 1,25-dihydroxyvitamin D 2 . 
     
     
         5 . The pharmaceutical composition of  claim 3 , wherein said at least one pharmaceutically acceptable excipient provides delayed release of 1,25-dihydroxyvitamin D 2 . 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the formulation is an oral formulation and said at least one pharmaceutically acceptable excipient provides delayed release of 1,25-dihydroxyvitamin D 2  to the small intestine of the patient. 
     
     
         7 . The pharmaceutical composition of  claim 5 , wherein the formulation is an oral formulation and said at least one pharmaceutically acceptable excipient provides delayed release of 1,25-dihydroxyvitamin D 2  to the ileum of the patient. 
     
     
         8 . A pharmaceutical composition having serum or plasma intact parathyroid hormone lowering activity, comprising an effective amount of 1,25-dihydroxyvitamin D 2  and at least one pharmaceutically acceptable excipient in an oral dosage form. 
     
     
         9 . The pharmaceutical composition of  claim 1 , comprising an intravenous formulation. 
     
     
         10 . The pharmaceutical composition of  claim 2 , wherein the unit dosage form comprises about 0.1 μg to about 10 μg of 1,25-dihydroxyvitamin D 2 . 
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein the unit dosage form comprises about 1 μg to about 4 μg of 1,25-dihydroxyvitamin D 2 . 
     
     
         12 . The pharmaceutical composition of  claim 10 , wherein the unit dosage form comprises about 2 μg to about 10 μg of 1,25-dihydroxyvitamin D 2 . 
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein the unit dosage form comprises about 3 μg to about 5 μg of 1,25-dihydroxyvitamin D 2 . 
     
     
         14 . The pharmaceutical composition of  claim 1 , comprising a solid or semi-solid, waxy mixture comprising a waxy controlled release carrier agent, a lipoidic agent, an oily vehicle for the vitamin D compound, and 1,25-dihydroxyvitamin D 2 . 
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the waxy controlled release carrier agent comprises a non-digestible wax. 
     
     
         16 . The pharmaceutical composition of  claim 14 , wherein the lipoidic agent includes a mixture of a lipophilic emulsifier which has an HLB value of less than 7 and an absorption enhancer which has an HLB value from 13 to 18. 
     
     
         17 . The pharmaceutical composition of  claim 14 , wherein the lipoidic agent comprises a polyglycolized glyceride. 
     
     
         18 . The pharmaceutical composition of  claim 14 , wherein the oily vehicle comprises a non-digestible oil. 
     
     
         19 . A pharmaceutical composition having serum or plasma intact parathyroid hormone lowering activity, comprising an effective amount of 1,25-dihydroxyvitamin D 2  and at least one pharmaceutically acceptable excipient, wherein said at least one pharmaceutically acceptable excipient is effective to control the release rate of 1,25-dihydroxyvitamin D 2  from the dosage form to reduce the maximum serum concentration of 1,25-dihydroxyvitamin D 2  in a dose interval (Cmax) and/or reduce the maximum change in serum concentration of 1,25-dihydroxyvitamin D 2  and/or increase the time for the plasma concentration of 1,25-dihydroxyvitamin D 2  to reach its maximum in a dose interval following administration (Tmax) and/or decrease a ratio of the maximum serum concentration of 1,25-dihydroxyvitamin D 2  within 24 hours after administration to the concentration 24 hours after administration (Cmax 24hr /C 24hr ), and/or increase the elimination half-life (t 1/2 ), as compared to either or both of (a) an equivalent amount of 1,25-dihydroxyvitamin D 2  administered by bolus IV injection and (b) the same dosage form omitting the effective amount of the release-modifying agent. 
     
     
         20 . The pharmaceutical composition of  claim 1 , comprising a solid or semi-solid, waxy mixture comprising paraffin wax, fatty acid mono- and di-glycerides, mineral oil, a polyglycolized glyceride, and 1,25-dihydroxyvitamin D 2 .