es, is a synthetically manufactured, metabolically active vitamin D analog of calcitriol with modifications to the side chain (D2 ) and the A (19-nor) ring. ZEMPLAR is available as soft gelatin capsules for oral administration containing 1microgram or 2micrograms of paricalcitol.
Each capsule also contains medium chain triglycerides, alcohol, and butylated hydroxytoluene. The medium chain triglycerides are fractionated from coconut oil or palm kernel oil.
The capsule shell is composed of gelatin, glycerin, titanium dioxide, iron oxide red (2 microgram capsules only), iron oxide yellow (2 microgram capsules only), iron oxide black (1 microgram capsules only), and water.
Paricalcitol is a white, crystalline powder with the empirical formula of C27 H44 O3 , which corresponds to a molecular weight of 416.64. Paricalcitol is chemically designated as 19-nor-1?,3,25-trihydroxy-9,10-secoergosta-5(Z),7(E),22(E)-triene
CLINICAL PHARMACOLOGY
Secondary hyperparathyroidism is characterized by an elevation in parathyroid hormone (PTH) associated with inadequate levels of active vitamin D hormone. The source of vitamin D in the body is from synthesis in the skin as vitamin D3 and from dietary intake as either vitamin D2 or D3 . Both vitamin D2 and D3require two sequential hydroxylations in the liver and the kidney to bind to and to activate the vitamin D receptor (VDR).
The endogenous VDR activator, calcitriol[1,25(OH)2 D3], is a hormone that binds to VDRs that are present in the parathyroid gland, intestine, kidney, and bone to maintain parathyroid function and calcium and phosphorus homeostasis, and to VDRs found in many other tissues, including prostate, endothelium and immune cells. VDR activation is essential for the proper formation and maintenance of normal bone.
In the diseased kidney, the activation of vitamin D is diminished, resulting in a rise of PTH, subsequently leading to secondary hyperparathyroidism and disturbances in the calcium and phosphorus homeostasis. Decreased levels of 1,25(OH)2 D3 have been observed in early stages of chronic kidney disease. The decreased levels of 1,25(OH)2 D3 and resultant elevated PTH levels, both of which often precede abnormalities in serum calcium and phosphorus, affect bone turnover rate and may result in renal osteodystrophy.
12.1 Mechanism of Action
Paricalcitol is a synthetic, biologically active vitamin D2 analog of calcitriol. Preclinical and in vitro studies have demonstrated that paricalcitol�s biological actions are mediated through binding of the VDR, which results in the selective activation of vitamin D responsive pathways. Vitamin D and paricalcitol have been shown to reduce parathyroid hormone levels by inhibiting PTH synthesis and secretion. |
