PARICALCITOL

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 Search

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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021606s004lbl.pdf
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/15733015

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 Target	Pharmacology	Condition	Potency
Vitamin D receptor 25 Target ID: CHEMBL1977 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021606s004lbl.pdf	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Secondary hyperparathyroidism associated with chronic kidney disease 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021606s004lbl.pdf	Primary		Approved 8429	ZEMPLAR Approved Use Paricalcitol is a vitamin D analog indicated for the prevention and treatment of secondary hyperparathyroidism associated with Chronic kidney disease (CKD) Stages 3 and 4 (1.1). CKD Stage 5 in patients on hemodialysis (HD) or peritoneal dialysis (PD) (1.2). 1.1 Chronic Kidney Disease Stages 3 and 4 Paricalcitol capsules are indicated for the prevention and treatment of secondary hyperparathyroidism associated with Chronic Kidney Disease (CKD) Stages 3 and 4. 1.2 Chronic Kidney Disease Stage 5 Paricalcitol capsules are indicated for the prevention and treatment of secondary hyperparathyroidism associated with CKD Stage 5 in patients on hemodialysis (HD) or peritoneal dialysis (PD)., 1.1 Chronic Kidney Disease Stages 3 and 4 Paricalcitol capsules are indicated for the prevention and treatment of secondary hyperparathyroidism associated with Chronic Kidney Disease (CKD) Stages 3 and 4., 1.2 Chronic Kidney Disease Stage 5 Paricalcitol capsules are indicated for the prevention and treatment of secondary hyperparathyroidism associated with CKD Stage 5 in patients on hemodialysis (HD) or peritoneal dialysis (PD). Launch Date 1998

C_max

Value	Dose	Co-administered	Analyte	Population
0.12 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021606s016s017lbl.pdf	1 μg 1 times / day multiple, oral dose: 1 μg route of administration: Oral experiment type: MULTIPLE co-administered:		PARICALCITOL plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: UNKNOWN food status: UNKNOWN
0.11 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021606s016s017lbl.pdf	1 μg 1 times / day multiple, oral dose: 1 μg route of administration: Oral experiment type: MULTIPLE co-administered:		PARICALCITOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
2.63 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021606s016s017lbl.pdf	1 μg 1 times / day multiple, oral dose: 1 μg route of administration: Oral experiment type: MULTIPLE co-administered:		PARICALCITOL plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: UNKNOWN food status: UNKNOWN
2.42 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021606s016s017lbl.pdf	1 μg 1 times / day multiple, oral dose: 1 μg route of administration: Oral experiment type: MULTIPLE co-administered:		PARICALCITOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
15 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021606s016s017lbl.pdf	1 μg 1 times / day multiple, oral dose: 1 μg route of administration: Oral experiment type: MULTIPLE co-administered:		PARICALCITOL plasma	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: UNKNOWN food status: UNKNOWN
16.8 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021606s016s017lbl.pdf	1 μg 1 times / day multiple, oral dose: 1 μg route of administration: Oral experiment type: MULTIPLE co-administered:		PARICALCITOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021606s016s017lbl.pdf	1 μg 1 times / day multiple, oral dose: 1 μg route of administration: Oral experiment type: MULTIPLE co-administered:		PARICALCITOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
16 ug 3 times / week steady, oral (starting) Dose: 16 ug, 3 times / week Route: oral Route: steady Dose: 16 ug, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/28332096	unhealthy, 13.9 years (range: 10-16 years) n = 18 Health Status: unhealthy Condition: stages 3 to 5 chronic kidney disease Age Group: 13.9 years (range: 10-16 years) Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/28332096	Other AEs: Hyperphosphatemia, Hypercalcemia... Other AEs: Hyperphosphatemia (2 patients) Hypercalcemia (3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/28332096
1 ug 1 times / day multiple, oral Dose: 1 ug, 1 times / day Route: oral Route: multiple Dose: 1 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23601186	unhealthy, 48.5 years n = 51 Health Status: unhealthy Age Group: 48.5 years Sex: M+F Population Size: 51 Sources: https://pubmed.ncbi.nlm.nih.gov/23601186	Disc. AE: Hypercalcemia... AEs leading to discontinuation/dose reduction: Hypercalcemia (29%) Sources: https://pubmed.ncbi.nlm.nih.gov/23601186
23 ug 1 times / week multiple, intravenous (starting) Dose: 23 ug, 1 times / week Route: intravenous Route: multiple Dose: 23 ug, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/22251408/	unhealthy, 53 ± 17 years (range: 18–83 years) n = 40 Health Status: unhealthy Condition: Secondary Hyperparathyroidism Age Group: 53 ± 17 years (range: 18–83 years) Sex: M+F Population Size: 40 Sources: https://pubmed.ncbi.nlm.nih.gov/22251408/	Disc. AE: Hyperphosphatemia, Hypercalcemia... AEs leading to discontinuation/dose reduction: Hyperphosphatemia (40%) Hypercalcemia (15%) Sources: https://pubmed.ncbi.nlm.nih.gov/22251408/

AEs

AE	Significance	Dose	Population
Hyperphosphatemia	2 patients	16 ug 3 times / week steady, oral (starting) Dose: 16 ug, 3 times / week Route: oral Route: steady Dose: 16 ug, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/28332096	unhealthy, 13.9 years (range: 10-16 years) n = 18 Health Status: unhealthy Condition: stages 3 to 5 chronic kidney disease Age Group: 13.9 years (range: 10-16 years) Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/28332096
Hypercalcemia	3 patients	16 ug 3 times / week steady, oral (starting) Dose: 16 ug, 3 times / week Route: oral Route: steady Dose: 16 ug, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/28332096	unhealthy, 13.9 years (range: 10-16 years) n = 18 Health Status: unhealthy Condition: stages 3 to 5 chronic kidney disease Age Group: 13.9 years (range: 10-16 years) Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/28332096
Hypercalcemia	29% Disc. AE	1 ug 1 times / day multiple, oral Dose: 1 ug, 1 times / day Route: oral Route: multiple Dose: 1 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23601186	unhealthy, 48.5 years n = 51 Health Status: unhealthy Age Group: 48.5 years Sex: M+F Population Size: 51 Sources: https://pubmed.ncbi.nlm.nih.gov/23601186
Hypercalcemia	15% Disc. AE	23 ug 1 times / week multiple, intravenous (starting) Dose: 23 ug, 1 times / week Route: intravenous Route: multiple Dose: 23 ug, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/22251408/	unhealthy, 53 ± 17 years (range: 18–83 years) n = 40 Health Status: unhealthy Condition: Secondary Hyperparathyroidism Age Group: 53 ± 17 years (range: 18–83 years) Sex: M+F Population Size: 40 Sources: https://pubmed.ncbi.nlm.nih.gov/22251408/
Hyperphosphatemia	40% Disc. AE	23 ug 1 times / week multiple, intravenous (starting) Dose: 23 ug, 1 times / week Route: intravenous Route: multiple Dose: 23 ug, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/22251408/	unhealthy, 53 ± 17 years (range: 18–83 years) n = 40 Health Status: unhealthy Condition: Secondary Hyperparathyroidism Age Group: 53 ± 17 years (range: 18–83 years) Sex: M+F Population Size: 40 Sources: https://pubmed.ncbi.nlm.nih.gov/22251408/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:7931	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7931
ChemicalBook	CB0500520	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0500520
MolPort	MolPort-006-167-660	https://www.molport.com/shop/molecule-link/MolPort-006-167-660
ZINC	ZINC000013911941	http://zinc15.docking.org/substances/ZINC000013911941

PubMed

Title	Date	PubMed
Transcriptional control of intestinal cytochrome P-4503A by 1alpha,25-dihydroxy vitamin D3.	2001 Dec	11723248
Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism.	2003 Apr	12631365
19-nor-1alpha,25-dihydroxyvitamin D(2) (paricalcitol): effects on clonal proliferation, differentiation, and apoptosis in human leukemic cell lines.	2003 Jan	12618899
Spotlight on paricalcitol in secondary hyperparathyroidism.	2005	15898824
Vitamin D treatment in chronic kidney disease.	2005 Jul-Aug	16076355
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
19-Nor-1,25(OH)2D2 (a novel, noncalcemic vitamin D analogue), combined with arsenic trioxide, has potent antitumor activity against myeloid leukemia.	2005 Mar 15	15781666
Calcification inhibitors and Wnt signaling proteins are implicated in bovine artery smooth muscle cell calcification in the presence of phosphate and vitamin D sterols.	2006 Dec	17171500
19nor-1,25-dihydroxyvitamin D2 specifically induces CYP3A9 in rat intestine more strongly than 1,25-dihydroxyvitamin D3 in vivo and in vitro.	2006 May	16484501
Combination therapy with an angiotensin-converting enzyme inhibitor and a vitamin D analog suppresses the progression of renal insufficiency in uremic rats.	2007 Jun	17513326
Differential effects of vitamin D analogs on vascular calcification.	2007 Jun	17352647
Elevated phosphorus modulates vitamin D receptor-mediated gene expression in human vascular smooth muscle cells.	2007 Nov	17715259
Effects of paricalcitol and enalapril on atherosclerotic injury in mouse aortas.	2010	20720404
Preventing progression of cardiac hypertrophy and development of heart failure by paricalcitol therapy in rats.	2011 Sep 1	21565836
Synergistic induction of human cathelicidin antimicrobial peptide gene expression by vitamin D and stilbenoids.	2014 Mar	24039193

Patents

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.

Name

Type

Language

PARICALCITOL

Official Name

English

PARICALCITOL [MART.]

Common Name

English

PARICALCITOL [USP IMPURITY]

Common Name

English

PARICALCITOL [MI]

Common Name

English

(7E,22E)-19-NOR-9,10-SECOERGOSTA-5,7,22-TRIENE-1.ALPHA.,3.BETA.,25-TRIOL

Common Name

English

COMPOUND 49510

Code

English

PARICALCITOL [VANDF]

Common Name

English

PARICALCITOL [USAN]

Common Name

English

PARICALCITOL [USP-RS]

Common Name

English

Paricalcitol [WHO-DD]

Common Name

English

(1.ALPHA.3.BETA.,7E,22E)-19-NOR-9,10-SECOERGOSTA-5,7,22-TRIENE-1,3,25-TRIOL

Common Name

English

PARICALCITOL [USP MONOGRAPH]

Common Name

English

ZEMPLAR

Brand Name

English

PARICALCITOL [ORANGE BOOK]

Common Name

English

COMPOUND-49510

Code

English

PARICALCITOL [HSDB]

Common Name

English

PARICALCITOL [JAN]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000006996