DESCRIPTION
Doxercalciferol, the active ingredient in Hectorol®, is a synthetic vitamin D2 analog that undergoes metabolic activation in vivo to form 1α,25-dihydroxyvitamin D2 (1α,25-(OH)2D2), a naturally occurring, biologically active form of vitamin D2. Hectorol is available as a sterile, clear, colorless aqueous solution for intravenous injection.
Hectorol single-use injection is supplied in a stoppered 2 mL amber glass vial containing either 4 mcg/2 mL or 2 mcg/mL. Each vial includes an aluminum seal and yellow (4 mcg/2 mL) or green (2 mcg/mL) flip-off cap. Each milliliter (mL) of solution contains doxercalciferol, 2 mcg; ethanol, 100%, 0.05 mL; Polysorbate 20, 10 mg; sodium chloride, 1.5 mg; butylated hydroxytoluene, 0.02 mg; sodium phosphate dibasic, heptahydrate, 14.4 mg; sodium phosphate monobasic, monohydrate, 1.8 mg; and disodium edetate, 1.1 mg.
Hectorol is also supplied as a multi-dose injection contained within a stoppered 2 mL amber glass vial containing 4 mcg/2 mL. Each vial includes an aluminum seal and an orange plastic flip-off cap. Each milliliter (mL) of solution contains doxercalciferol, 2 mcg; ethanol, 100%, 0.075 mL; Polysorbate 20, 10 mg; sodium chloride, 1.5 mg; butylated hydroxytoluene, 0.02 mg; sodium phosphate dibasic, heptahydrate, 14.4 mg; sodium phosphate monobasic, monohydrate, 1.8 mg; and disodium edetate, 1.1 mg.
Doxercalciferol is a colorless crystalline compound with a calculated molecular weight of 412.66 and a molecular formula of C28H44O2. It is soluble in oils and organic solvents, but is relatively insoluble in water. Chemically, doxercalciferol is (1α,3β,5Z,7E,22E)-9,10-secoergosta-5,7,10(19),22-tetraene-1,3-diol and has the structural formula presented in Figure 1.
|
Figure 1: Chemical Structure of Doxercalciferol |
 |
Other names frequently used for doxercalciferol are 1α-hydroxyvitamin D2, 1α-OH-D2, and 1α-hydroxyergocalciferol.
CLINICAL PHARMACOLOGY
Vitamin D levels in humans depend on two sources: (1) exposure to the ultraviolet rays of the sun for conversion of 7-dehydrocholesterol in the skin to vitamin D3 (cholecalciferol) and (2) dietary intake of either vitamin D2 (ergocalciferol) or vitamin D3. Vitamin D2 and vitamin D3 must be metabolically activated in the liver and kidney before becoming fully active on target tissues. The initial step in the activation process is the introduction of a hydroxyl group in the side chain at C-25 by the hepatic enzyme, CYP 27 (a vitamin D-25-hydroxylase). The products of this reaction are 25-(OH)D2 and 25-(OH)D3, respectively. Further hydroxylation of these metabolites occurs in the mitochondria of kidney tissue, catalyzed by renal 25-hydroxyvitamin D-1-α-hydroxylase to produce 1α,25-(OH)2D2, the primary biologically active form of vitamin D2, and 1α,25-(OH)2D3 (calcitriol), the biologically active form of vitamin D3.
Mechanism of Action
Calcitriol (1α,25-(OH)2D3) and 1α,25-(OH)2D2 regulate blood calcium at levels required for essential body functions. Specifically, the biologically active vitamin D metabolites control the intestinal absorption of dietary calcium, the tubular reabsorption of calcium by the kidney and, in conjunction with parathyroid hormone (PTH), the mobilization of calcium from the skeleton. They act directly on bone cells (osteoblasts) to stimulate skeletal growth, and on the parathyroid glands to suppress PTH synthesis and secretion. These functions are mediated by the interaction of these biologically
