Paricalcitol

Absorption

Well absorbed

Description

Paricalcitol was launched as Zemplar in the US for the prevention and treatment of secondary hyperthyroidism associated with chronic renal failure. Paricalcitol is a synthetic vitamin D2, namely a novel 1-alpha-hydroxy-19-noranalogue in which the ring A exocyclic methylene group, typical of all vitamin D systems, has been replaced by two hydrogen atoms. Paricalcitol is the first vitamin D analogue marketed for this indication. In patients with chronic renal failure, Paricalcitol appreciably reduced levels of parathyroid hormone (PTH) without a significant difference in the incidence rate for hypercalcemia or hyperphosphatemia when compared with placebo.

Description

Paricalcitol is a synthetic 1,25-dihydroxy vitamin D₂ analog. As vitamin D deficiency, associated with chronic kidney disease, leads to an increase in parathyroid hormone (secondary hyperparathyroidism), paricalcitol is used in renal patients to block parathyroid hormone overproduction. Vitamin D deficiency is also a risk factor in cancer, cardiovascular disease, hypertension, and diabetes, and paricalcitol may have applications in those contexts as well.

Chemical properties

White Solid

Originator

Abbott (US)

The Uses of Paricalcitol

1,25-Dihydroxy vitamin D2 is a potent agonist of the vitamin D receptor. Paricalcitol is a synthetic 1,25-dihydroxy vitamin D2 analog. As vitamin D deficiency, associated with chronic kidney disease, leads to an increase in parathyroid hormone (secondary hyperparathyroidism), paricalcitol is used in renal patients to block parathyroid hormone overproduction. Vitamin D deficiency is also a risk factor in cancer, cardiovascular disease, hypertension, and diabetes, and paricalcitol may have applications in those contexts as well.

The Uses of Paricalcitol

Synthetic analog of vitamin D. Antihyperparathyroid.

The Uses of Paricalcitol

Antihyperparathyriod

Background

Paricalcitol is a synthetic vitamin D analog. Paricalcitol has been used to reduce parathyroid hormone levels. Paricalcitol is indicated for the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure.

Indications

For treatment of secondary hyperparathyroidism associated with chronic kidney disease (CKD) Stage 3 and 4

Definition

ChEBI: Paricalcitol is a seco-cholestane and a hydroxy seco-steroid. It has a role as an antiparathyroid drug. It is functionally related to a vitamin D2.

brand name

Zemplar (Abbott).

Pharmacokinetics

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.1 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. An in vitro study indicates that paricalcitol is not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A at concentrations up to 50 nM (21 ng/mL).

Clinical Use

Vitamin D analogue:
Treatment and prevention of secondary hyperparathyroidism associated with chronic renal failure

Metabolism

Metabolized by multiple hepatic and non-hepatic enzymes, including mitochondrial CYP24, as well as CYP3A4 and UGT1A4

Metabolism

Extensively metabolised via hepatic and non-hepatic pathways to form two relatively inactive metabolites. After oral administration of 3 H-paricalcitol, only about 2% of the dose was eliminated unchanged in the faeces, and no parent drug found in the urine.
Approximately 70% of the radioactivity was eliminated in the faeces and 18% was recovered in the urine. Most of the systemic exposure was from the parent drug.