Identification

Name
Paricalcitol
Accession Number
DB00910
Description

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.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 416.6365
Monoisotopic: 416.329045274
Chemical Formula
C27H44O3
Synonyms
  • 19-Nor-1alpha,25-dihydroxyvitamin D2
  • Paricalcitol
External IDs
  • COMPOUND 49510
  • COMPOUND-49510

Pharmacology

Indication

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

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

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).

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 andin 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.

TargetActionsOrganism
AVitamin D3 receptor
agonist
Humans
Absorption

Well absorbed

Volume of distribution
  • 30.8 ± 7.5 L [CKD Stage 5-HD]
  • 34.9 ± 9.5 L [CKD Stage 5-PD]
  • 23.8 L [healthy subjects]
Protein binding

99.8% (bound to plasma proteins)

Metabolism

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

Route of elimination

Paricalcitol is excreted primarily by hepatobiliary excretion.

Half-life

4 to 6 hours

Clearance
  • 1.49 +/- 0.60 L/h [chronic kidney disease Stage 5 with hemodialysis]
  • 1.54 +/- 0.95 L/h [chronic kidney disease Stage 5with peritoneal dialysis]
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Paricalcitol can be increased when it is combined with Abametapir.
AcetyldigitoxinThe risk or severity of ventricular arrhythmias and Cardiac Arrhythmia can be increased when Paricalcitol is combined with Acetyldigitoxin.
AlfacalcidolThe risk or severity of adverse effects can be increased when Paricalcitol is combined with Alfacalcidol.
Aluminum hydroxideThe serum concentration of Aluminum hydroxide can be increased when it is combined with Paricalcitol.
Beclomethasone dipropionateThe therapeutic efficacy of Paricalcitol can be decreased when used in combination with Beclomethasone dipropionate.
BendroflumethiazideThe risk or severity of hypercalcemia can be increased when Bendroflumethiazide is combined with Paricalcitol.
BenzthiazideThe risk or severity of hypercalcemia can be increased when Benzthiazide is combined with Paricalcitol.
BetamethasoneThe therapeutic efficacy of Paricalcitol can be decreased when used in combination with Betamethasone.
Betamethasone phosphateThe therapeutic efficacy of Paricalcitol can be decreased when used in combination with Betamethasone phosphate.
BudesonideThe therapeutic efficacy of Paricalcitol can be decreased when used in combination with Budesonide.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
  • Avoid antacids. Avoid taking aluminum-containing antacids chronically with paricalcitol as there is an increased risk of aluminum toxicity.
  • Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4, and paricalcitol metabolism is mediated partially through CYP3A4; therefore, grapefruit may increase paricalcitol serum levels.
  • Take with or without food.

Products

Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ParicalcitolInjection5 ug/1mLIntravenousWest-Ward Pharmaceuticals Corp2014-11-18Not applicableUS flag
ParicalcitolInjection, solution2 ug/1mLIntravenousAccord Healthcare, Inc.2016-03-24Not applicableUS flag
ParicalcitolInjection5 ug/1mLIntravenousWest-Ward Pharmaceuticals Corp2014-11-18Not applicableUS flag
ParicalcitolInjection, solution2 ug/1mLIntravenousHospira, Inc.2014-12-01Not applicableUS flag
ParicalcitolInjection, solution5 ug/1mLIntravenousAccord Healthcare, Inc.2016-03-24Not applicableUS flag
ParicalcitolInjection2 ug/1mLIntravenousWest-Ward Pharmaceuticals Corp2014-11-18Not applicableUS flag
ParicalcitolInjection, solution5 ug/1mLIntravenousHospira, Inc.2014-11-01Not applicableUS flag
ZemplarSolution5 mcgIntravenousAbbvie2005-12-012012-11-03Canada flag
ZemplarInjection, solution2 ug/1mLIntravenousAbbVie Inc.1998-04-17Not applicableUS flag
ZemplarCapsule, liquid filled4 ug/1OralAbbott Laboratories2006-07-122006-07-12US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ParicalcitolCapsule1 ug/1OralAlvogen, Inc.2018-01-01Not applicableUS flag
ParicalcitolInjection10 ug/2mLIntravenousAmneal Pharmaceuticals LLC2017-03-09Not applicableUS flag
ParicalcitolCapsule, liquid filled2 ug/1OralZydus Pharmaceuticals USA Inc2010-06-142020-04-23US flag
ParicalcitolCapsule4 ug/1OralLotus Pharmaceutical Co., Ltd. Nantou Plant2017-03-31Not applicableUS flag
ParicalcitolCapsule1 ug/1OralGolden State Medical Supply, Inc.2014-03-27Not applicableUS flag
ParicalcitolCapsule1 ug/1OralBionpharma Inc.2016-08-16Not applicableUS flag
ParicalcitolInjection, solution5 ug/1mLIntravenousDr. Reddy's Laboratories, Inc.2016-09-06Not applicableUS flag
ParicalcitolCapsule1 mg/1OralBanner Life Sciences Llc.2015-09-02Not applicableUS flag
ParicalcitolCapsule2 mg/1OralBanner Life Sciences Llc.2015-10-01Not applicableUS flag
ParicalcitolCapsule, liquid filled2 ug/1OralTeva2013-09-302017-03-31US flag00093 7657 56 nlmimage10 5e382f71
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

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Categories

ATC Codes
H05BX02 — Paricalcitol
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as vitamin d and derivatives. These are compounds containing a secosteroid backbone, usually secoergostane or secocholestane.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Vitamin D and derivatives
Direct Parent
Vitamin D and derivatives
Alternative Parents
Triterpenoids / Tertiary alcohols / Secondary alcohols / Cyclic alcohols and derivatives / Hydrocarbon derivatives
Substituents
Alcohol / Aliphatic homopolycyclic compound / Cyclic alcohol / Hydrocarbon derivative / Organic oxygen compound / Organooxygen compound / Secondary alcohol / Tertiary alcohol / Triterpenoid
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
seco-cholestane, hydroxy seco-steroid (CHEBI:7931) / Vitamin D2 and derivatives (C08127) / C27 bile acids, alcohols, and derivatives (LMST04030163)

Chemical Identifiers

UNII
6702D36OG5
CAS number
131918-61-1
InChI Key
BPKAHTKRCLCHEA-UBFJEZKGSA-N
InChI
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
IUPAC Name
(1R,3R)-5-{2-[(1R,3aS,4E,7aR)-1-[(2R,3E,5S)-6-hydroxy-5,6-dimethylhept-3-en-2-yl]-7a-methyl-octahydro-1H-inden-4-ylidene]ethylidene}cyclohexane-1,3-diol
SMILES

References

Synthesis Reference

Anchel Schwartz, Alexei Ploutno, Koby Wolfman, "Preparation of paricalcitol." U.S. Patent US20070149489, issued June 28, 2007.

US20070149489
General References
Not Available
Human Metabolome Database
HMDB0015046
KEGG Drug
D00930
KEGG Compound
C08127
PubChem Compound
5281104
PubChem Substance
46505780
ChemSpider
4444552
BindingDB
233195
RxNav
73710
ChEBI
7931
ChEMBL
CHEMBL1200622
ZINC
ZINC000013911941
Therapeutic Targets Database
DAP000211
PharmGKB
PA450798
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Paricalcitol
FDA label
Download (447 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentEndstage Renal Disease / Hyperparathyroidism, Secondary1
4CompletedPreventionChronic Kidney Disease (CKD)1
4CompletedPreventionChronic Kidney Disease (CKD) / Coronary Calcification / Deficiency, Vitamin D / Disorders of Calcium and Bone Metabolism1
4CompletedPreventionRenal Failure1
4CompletedTreatmentAnemia / Chronic Kidney Disease (CKD)1
4CompletedTreatmentCardiorenal Syndrome / Chronic Allograft Nephropathy (CAN)1
4CompletedTreatmentCardiovascular Heart Disease / Nephropathy, Diabetic1
4CompletedTreatmentChronic Kidney Disease (CKD) / Hemodialysis Treatment / Hyperparathyroidism, Secondary1
4CompletedTreatmentChronic Kidney Disease (CKD) / Hyperparathyroidism, Secondary3
4CompletedTreatmentChronic Renal Failure (CRF)1

Pharmacoeconomics

Manufacturers
  • Abbott laboratories pharmaceutical products div
  • Abbott laboratories
Packagers
  • Abbott Laboratories Ltd.
  • Cardinal Health
  • Catalent Pharma Solutions
  • Hospira Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Remedy Repack
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous10 mcg/2ml
Injection, solutionIntravenous5 mcg/ml
Injection, solutionParenteral2 MCG/ML
Injection, solutionParenteral5 MCG/ML
Injection, solutionParenteral2 MICROGRAMMI/ML
Injection, solutionParenteral5 MICROGRAMMI/ML
CapsuleOral2 MICROGRAMMI
Injection, solutionIntravenous2 mcg/ml
CapsuleOral1 mg/1
CapsuleOral1 ug/1
CapsuleOral2 mg/1
CapsuleOral2 ug/1
CapsuleOral4 ug/1
CapsuleOral4 mg/1
Capsule, gelatin coatedOral1 ug/1
Capsule, gelatin coatedOral2 ug/1
Capsule, gelatin coatedOral4 ug/1
Capsule, liquid filledOral1 ug/1
Capsule, liquid filledOral2 ug/1
Capsule, liquid filledOral4 ug/1
InjectionIntravenous10 ug/2mL
InjectionIntravenous2 ug/1mL
InjectionIntravenous5 ug/1mL
Injection, solutionIntravenous2 ug/1mL
Injection, solutionIntravenous5 ug/1mL
Injection, solutionIntravenous5 mcg/1ml
CapsuleOral1 MCG
CapsuleOral2 MCG
CapsuleOral4 MCG
Injection, solution2 MCG/ML
Injection, solution5 MCG/ML
Capsule1 mcg
Capsule2 mcg
Injection2 mcg/ml
Capsule4 mcg
Injection5 mcg/ml
CapsuleOral
SolutionIntravenous5 mcg
Capsule, liquid filledOral1 cg
Capsule, liquid filledOral2 mcg
Injection10 mcg/2ml
Prices
Unit descriptionCostUnit
Zemplar 4 mcg capsule37.58USD capsule
Zemplar 5 mcg/ml vial28.03USD ml
Zemplar 2 mcg capsule18.79USD capsule
Zemplar 2 mcg/ml vial11.22USD ml
Zemplar 1 mcg capsule9.39USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5246925No1993-09-212012-04-17US flag
US5597815Yes1997-01-282016-01-13US flag
US6361758Yes2002-03-262018-10-08US flag
US6136799Yes2000-10-242018-10-08US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
logP4.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0068 mg/mLALOGPS
logP5.27ALOGPS
logP4.26ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)14.81ChemAxon
pKa (Strongest Basic)-1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area60.69 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity127.95 m3·mol-1ChemAxon
Polarizability51.06 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9971
Blood Brain Barrier+0.795
Caco-2 permeable+0.776
P-glycoprotein substrateSubstrate0.7667
P-glycoprotein inhibitor INon-inhibitor0.7431
P-glycoprotein inhibitor IINon-inhibitor0.8491
Renal organic cation transporterNon-inhibitor0.8292
CYP450 2C9 substrateNon-substrate0.7968
CYP450 2D6 substrateNon-substrate0.8903
CYP450 3A4 substrateSubstrate0.7662
CYP450 1A2 substrateNon-inhibitor0.8127
CYP450 2C9 inhibitorNon-inhibitor0.8277
CYP450 2D6 inhibitorNon-inhibitor0.948
CYP450 2C19 inhibitorNon-inhibitor0.8491
CYP450 3A4 inhibitorNon-inhibitor0.8409
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6631
Ames testNon AMES toxic0.9116
CarcinogenicityNon-carcinogens0.9111
BiodegradationNot ready biodegradable0.988
Rat acute toxicity4.4277 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9069
hERG inhibition (predictor II)Non-inhibitor0.8015
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Recruited to promoters via its interaction with BAZ1B...
Gene Name
VDR
Uniprot ID
P11473
Uniprot Name
Vitamin D3 receptor
Molecular Weight
48288.64 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Andress DL: Vitamin D treatment in chronic kidney disease. Semin Dial. 2005 Jul-Aug;18(4):315-21. [PubMed:16076355]
  4. Brancaccio D, Cozzolino M, Pasho S, Fallabrino G, Olivi L, Gallieni M: New acquisitions in therapy of secondary hyperparathyroidism in chronic kidney disease and peritoneal dialysis patients: role of vitamin D receptor activators. Contrib Nephrol. 2009;163:219-26. doi: 10.1159/000223802. Epub 2009 Jun 3. [PubMed:19494617]
  5. Wu-Wong JR, Nakane M, Gagne GD, Brooks KA, Noonan WT: Comparison of the pharmacological effects of paricalcitol and doxercalciferol on the factors involved in mineral homeostasis. Int J Endocrinol. 2010;2010:621687. doi: 10.1155/2010/621687. Epub 2010 Mar 2. [PubMed:20204178]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity
Specific Function
Has a role in maintaining calcium homeostasis. Catalyzes the NADPH-dependent 24-hydroxylation of calcidiol (25-hydroxyvitamin D(3)) and calcitriol (1-alpha,25-dihydroxyvitamin D(3)). The enzyme can...
Gene Name
CYP24A1
Uniprot ID
Q07973
Uniprot Name
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial
Molecular Weight
58874.695 Da
References
  1. Robinson DM, Scott LJ: Paricalcitol: a review of its use in the management of secondary hyperparathyroidism. Drugs. 2005;65(4):559-76. [PubMed:15733015]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A4
Uniprot ID
P22310
Uniprot Name
UDP-glucuronosyltransferase 1-4
Molecular Weight
60024.535 Da

Drug created on June 13, 2005 07:24 / Updated on June 12, 2020 10:51

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