ZEMPLAR - paricalcitol injection, solution
Abbott Laboratories
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ZEMPLAR®
(paricalcitol) Injection
Fliptop Vial
DESCRIPTION
Paricalcitol, USP, the active ingredient in Zemplar Injection, is a synthetically manufactured analog of calcitriol, the metabolically active form of vitamin D indicated for the prevention and treatment of secondary hyperparathyroidism associated with chronic kidney disease(CKD) Stage 5. Zemplar is available as a sterile, clear, colorless, aqueous solution for intravenous injection. Each mL contains paricalcitol, 2 mcg or 5 mcg and the following inactive ingredients: alcohol, 20% (v/v) and propylene glycol, 30% (v/v).
Paricalcitol is a white powder chemically designated as 19-nor-1α,3β,25-trihydroxy-9,10-secoergosta-5(Z),7(E),22(E)-triene and has the following structural formula:
Molecular formula is C27H44O3.
Molecular weight is 416.64.
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 and from dietary intake. Vitamin D requires 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. 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.
Mechanism of Action
Paricalcitol is a synthetic, biologically active vitamin D analog of calcitriol with modifications to the side chain (D2) and the A (19-nor) ring. 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.
Pharmacokinetics
Within two hours after administering Zemplar intravenous doses ranging from 0.04 to 0.24 mcg/kg, concentrations of paricalcitol decreased rapidly; thereafter, concentrations of paricalcitol declined log-linearly. No accumulation of paricalcitol was observed with three times a week dosing.
Distribution
Paricalcitol is extensively bound to plasma proteins (≥99.8%). In healthy subjects, the steady state volume of distribution is approximately 23.8 L. The mean volume of distribution following a 0.24 mcg/kg dose of paricalcitol in CKD Stage 5 subjects requiring hemodialysis (HD) and peritoneal dialysis (PD) is between 31 and 35 L.
Metabolism
After IV administration of a 0.48 mcg/kg dose of 3H-paricalcitol, parent drug was extensiv
