Doxercalciferol

Doxercalciferol is a synthetic vitamin D₂ analog that requires metabolic activation to form the active 1α,25-(OH)₂D₂ metabolite, which binds to the vitamin D receptor (VDR) to result in the selective activation of vitamin D responsive pathways. Vitamin D and doxercalciferol have been shown to reduce PTH levels by inhibiting PTH synthesis and secretion.

Absorption

In healthy volunteers, peak blood levels of 1α,25-(OH)₂D₂, the major metabolite of doxercalciferol, are attained at 8 hours after a single intravenous dose of doxercalciferol and at 11 to 12 hours following capsule doses.

Elimination

The mean elimination half-life of 1α,25-(OH)₂D₂ after an oral dose is approximately 32 to 37 hours with a range of up to 96 hours.

Metabolism

Doxercalciferol is activated by CYP 27 in the liver to form 1α,25-(OH)₂D₂ (major metabolite) and 1α,24-dihydroxyvitamin D₂ (minor metabolite). Activation of doxercalciferol does not require the involvement of the kidneys.

Specific Populations

Patients with renal impairment

The mean elimination half-life of 1α,25-(OH)₂D₂ in patients with end-stage renal disease (ESRD) and in healthy volunteers appears to be similar following an oral dose. Hemodialysis causes a temporary increase in 1α,25-(OH)₂D₂ mean concentrations, presumably due to volume contraction. 1α,25-(OH)₂D₂ is not removed from blood during hemodialysis.