Paricalcitol (DB00910): A Comprehensive Monograph on a Selective Vitamin D Receptor Activator

1.0 Executive Summary

Paricalcitol is a synthetic, biologically active analog of vitamin D, chemically identified as 19-nor-1α,25-dihydroxyvitamin D2.[1] It functions as a selective agonist for the Vitamin D Receptor (VDR), a nuclear receptor that modulates gene expression in a wide array of tissues.[1] The primary clinical application of paricalcitol is the prevention and treatment of secondary hyperparathyroidism (SHPT), a common and serious complication of chronic kidney disease (CKD) in patients with Stage 3, 4, or 5 disease.[1]

The therapeutic rationale for paricalcitol's development was to create a VDR activator that could potently suppress the synthesis and secretion of parathyroid hormone (PTH) while exhibiting a reduced impact on intestinal calcium absorption and bone calcium mobilization. This selective action aims to mitigate the risks of hypercalcemia and hyperphosphatemia, which are dose-limiting toxicities of older, non-selective VDR activators like calcitriol, and are associated with an increased risk of vascular calcification and cardiovascular mortality.[4]

The principal safety concerns associated with paricalcitol therapy are directly related to its mechanism of action and include hypercalcemia, hyperphosphatemia, and the potential for excessive PTH suppression, which can lead to adynamic bone disease.[8] Its metabolism is significantly mediated by the cytochrome P450 3A4 (CYP3A4) enzyme, creating a high potential for clinically significant drug-drug interactions, particularly in the CKD population, which is characterized by polypharmacy. This necessitates diligent patient monitoring and careful dose adjustments when co-administered with potent CYP3A4 inhibitors or inducers.[10]