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Details

Stereochemistry ABSOLUTE
Molecular Formula C27H44O3
Molecular Weight 416.6365
Optical Activity UNSPECIFIED
Defined Stereocenters 7 / 7
E/Z Centers 2
Charge 0

SHOW SMILES / InChI
Structure of PARICALCITOL

SMILES

[H][C@@]1(CC[C@@]2([H])\C(CCC[C@]12C)=C\C=C3C[C@@H](O)C[C@H](O)C3)[C@H](C)\C=C\[C@H](C)C(C)(C)O

InChI

InChIKey=BPKAHTKRCLCHEA-UBFJEZKGSA-N
InChI=1S/C27H44O3/c1-18(8-9-19(2)26(3,4)30)24-12-13-25-21(7-6-14-27(24,25)5)11-10-20-15-22(28)17-23(29)16-20/h8-11,18-19,22-25,28-30H,6-7,12-17H2,1-5H3/b9-8+,21-11+/t18-,19+,22-,23-,24-,25+,27-/m1/s1

HIDE SMILES / InChI

Molecular Formula C27H44O3
Molecular Weight 416.6365
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 7 / 7
E/Z Centers 2
Optical Activity UNSPECIFIED

Description

Paricalcitol (Zemplar) is a synthetic vitamin D(2) analogue that inhibits the secretion of parathyroid hormone (PTH) through binding to the vitamin D receptor. It is approved in the US and in most European nations for intravenous use in the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure in adult, and in the US paediatric, patients. Paricalcitol effectively reduced elevated serum PTH levels and was generally well tolerated in children and adults with secondary hyperparathyroidism associated with chronic renal failure. In well designed clinical trials, paricalcitol was as effective as calcitriol and as well tolerated in terms of the incidence of prolonged hypercalcaemia and/or elevated calcium-phosphorus product (Ca x P). Preclinical and in vitro studies have demonstrated that paricalcitol's biological actions are mediated through binding of the vitamin D receptor, 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.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ZEMPLAR

Cmax

ValueDoseCo-administeredAnalytePopulation
0.12 ng/mL
1 μg 1 times / day multiple, oral
PARICALCITOL plasma
Homo sapiens
0.11 ng/mL
1 μg 1 times / day multiple, oral
PARICALCITOL plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
2.63 ng × h/mL
1 μg 1 times / day multiple, oral
PARICALCITOL plasma
Homo sapiens
2.42 ng × h/mL
1 μg 1 times / day multiple, oral
PARICALCITOL plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
15 h
1 μg 1 times / day multiple, oral
PARICALCITOL plasma
Homo sapiens
16.8 h
1 μg 1 times / day multiple, oral
PARICALCITOL plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
0.2%
1 μg 1 times / day multiple, oral
PARICALCITOL plasma
Homo sapiens

Doses

AEs

PubMed

Sample Use Guides

In Vivo Use Guide
ZEMPLAR® (paricalcitol) Capsules indicated for the prevention and treatment of secondary hyperparathyroidism in chronic kidney disease (CKD). Zemplar Capsules may be administered daily or three times a week. When dosing three times weekly, the dose should be administered no more frequently than every other day. The average weekly doses for both daily and three times a week dosage regimens are similar Zemplar Capsules may be taken without regard to food. No dosing adjustment is required in patients with mild and moderate hepatic impairment. The initial dose of Zemplar Capsules for CKD Stage 3 and 4 patients is based on baseline intact parathyroid hormone (iPTH) levels: 1 mcg daily dose if iPTH levels ≤ 500 pg/mL, 2 mcg daily dose if iPTH levels > 500 pg/mL. Dosing must be individualized and based on serum or plasma iPTH levels, with monitoring of serum calcium and serum phosphorus. The initial dose of Zemplar Capsules for CKD Stage 5 in micrograms is based on a baseline iPTH level (pg/mL)/80. To minimize the risk of hypercalcemia patients should be treated only after their baseline serum calcium has been adjusted to 9.5 mg/dL or lower. ZEMPLAR® (paricalcitol) Injection indicated for the prevention and treatment of secondary hyperparathyroidism associated with chronic kidney disease(CKD) Stage 5. The currently accepted target range for iPTH levels in CKD Stage 5 patients is no more than 1.5 to 3 times the non-uremic upper limit of normal. The recommended initial dose of Zemplar is 0.04 mcg/kg to 0.1 mcg/kg (2.8 – 7 mcg) administered as a bolus dose no more frequently than every other day at any time during dialysis.
Route of Administration: Other
In Vitro Use Guide
Paricalcitol (1 nM to 1 uM) inhibits the TNF-α–mediated RANTES expression in human tubular epithelial cells in vitro. Paricalcitol reduces the chemoattraction of tubular epithelial cells to splenocytes and THP-1 cells in vitro.
Substance Class Chemical
Record UNII
6702D36OG5
Record Status Validated (UNII)
Record Version