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Identification
NameParicalcitol
Accession NumberDB00910  (APRD01165)
TypeSmall Molecule
GroupsApproved, Investigational
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.

Structure
Thumb
Synonyms
19-Nor-1alpha,25-dihydroxyvitamin D2
Paricalcitol
Zemplar
External Identifiers Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Paricalcitolinjection, solution2 ug/mLintravenousHospira, Inc.2014-11-01Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolinjection2 ug/mLintravenousWest ward Pharmaceutical Corp2014-11-18Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolinjection5 ug/mLintravenousWest ward Pharmaceutical Corp2014-11-18Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolinjection5 ug/mLintravenousWest ward Pharmaceutical Corp2014-11-18Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, liquid filled2 ug/1oralZydus Pharmaceuticals USA Inc2010-06-14Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, liquid filled1 ug/1oralZydus Pharmaceuticals USA Inc2010-06-14Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolinjection, solution5 ug/mLintravenousHospira, Inc.2014-11-01Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Zemplarinjection, solution5 ug/mLintravenousAbb Vie Inc.1998-04-17Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Zemplarsolution5 mcgintravenousAbbvie Corporation2005-12-012012-11-03Canada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Zemplarcapsule, liquid filled4 ug/1oralAbb Vie Inc.2010-06-142015-12-29Us 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Zemplarinjection, solution2 ug/mLintravenousAbb Vie Inc.1998-04-17Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Zemplarcapsule, liquid filled1 ug/1oralAbb Vie Inc.2010-06-14Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Zemplarcapsule, liquid filled1 ug/1oralCardinal Health2005-05-26Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Zemplarcapsule, liquid filled2 ug/1oralAbb Vie Inc.2010-06-14Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Paricalcitolcapsule2 mg/1oralBanner Life Sciences Llc.2015-10-01Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, liquid filled1 ug/1oralTeva Pharmaceuticals USA Inc2013-09-30Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, liquid filled2 ug/1oralDr. Reddy's Laboratories Limited2014-06-25Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, liquid filled4 ug/1oralAurobindo Pharma Limited2016-01-14Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, gelatin coated2 ug/1oralRising Pharmaceuticals, Inc.2015-11-03Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, liquid filled1 ug/1oralDr. Reddy's Laboratories Limited2014-06-25Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, liquid filled2 ug/1oralAurobindo Pharma Limited2016-01-14Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, gelatin coated1 ug/1oralRising Pharmaceuticals, Inc.2015-11-03Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, liquid filled4 ug/1oralBanner Pharmacaps2014-03-27Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, liquid filled1 ug/1oralAurobindo Pharma Limited2016-01-14Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, liquid filled1 ug/1oralAmerican Health Packaging2015-03-31Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, liquid filled2 ug/1oralBanner Pharmacaps2014-03-27Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule4 ug/1oralAmneal Pharmaceuticals of New York, LLC2016-01-17Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, liquid filled4 ug/1oralGolden State Medical Supply, Inc.2014-03-27Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, liquid filled1 ug/1oralBanner Pharmacaps2014-03-27Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule2 ug/1oralAmneal Pharmaceuticals of New York, LLC2016-01-17Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, liquid filled2 ug/1oralGolden State Medical Supply, Inc.2014-04-23Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, liquid filled4 ug/1oralTeva Pharmaceuticals USA Inc2013-09-30Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule1 ug/1oralAmneal Pharmaceuticals of New York, LLC2016-01-17Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, liquid filled1 ug/1oralGolden State Medical Supply, Inc.2014-04-23Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule1 mg/1oralBanner Life Sciences Llc.2015-09-02Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule4 mg/1oralBanner Life Sciences Llc.2015-10-01Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, liquid filled2 ug/1oralTeva Pharmaceuticals USA Inc2013-09-30Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, liquid filled4 ug/1oralDr. Reddy's Laboratories Limited2014-06-25Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Paricalcitolcapsule, gelatin coated4 ug/1oralRising Pharmaceuticals, Inc.2015-11-03Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
CAS number131918-61-1
WeightAverage: 416.6365
Monoisotopic: 416.329045274
Chemical FormulaC27H44O3
InChI KeyInChIKey=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
[H]C1CC[C@]2(C)[C@]([H])(CC[C@@]2([H])\C1=C\C=C1C[C@@H](O)C[C@H](O)C1)[C@H](C)\C=C\[C@H](C)C(O)(C)C
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as triterpenoids. These are terpene molecules containing 8 isoprene units.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassTriterpenoids
Direct ParentTriterpenoids
Alternative Parents
Substituents
  • Polycyclic triterpenoid
  • Triterpenoid
  • Cyclohexanol
  • Tertiary alcohol
  • Cyclic alcohol
  • Secondary alcohol
  • Hydrocarbon derivative
  • Organooxygen compound
  • Alcohol
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
Pharmacology
IndicationFor treatment of secondary hyperparathyroidism associated with chronic kidney disease (CKD) Stage 3 and 4
PharmacodynamicsSecondary 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 actionParicalcitol 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.
AbsorptionWell 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 binding99.8% (bound to plasma proteins)
Metabolism

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

Route of eliminationParicalcitol is excreted primarily by hepatobiliary excretion.
Half life4 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]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Abbott laboratories pharmaceutical products div
  • Abbott laboratories
Packagers
Dosage forms
FormRouteStrength
Capsuleoral1 mg/1
Capsuleoral1 ug/1
Capsuleoral2 ug/1
Capsuleoral2 mg/1
Capsuleoral4 mg/1
Capsuleoral4 ug/1
Capsule, gelatin coatedoral1 ug/1
Capsule, gelatin coatedoral2 ug/1
Capsule, gelatin coatedoral4 ug/1
Capsule, liquid filledoral4 ug/1
Injectionintravenous2 ug/mL
Injectionintravenous5 ug/mL
Capsule, liquid filledoral1 ug/1
Capsule, liquid filledoral2 ug/1
Injection, solutionintravenous2 ug/mL
Injection, solutionintravenous5 ug/mL
Solutionintravenous5 mcg
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
CountryPatent NumberApprovedExpires (estimated)
United States52469251995-04-172012-04-17
United States61367991998-10-082018-10-08
Properties
StateSolid
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
Polarizability51.11 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

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

US20070149489
General ReferencesNot Available
External Links
ATC CodesH05BX02
AHFS Codes
  • 88:16.00
PDB EntriesNot Available
FDA labelDownload (447 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
Aluminum hydroxideThe serum concentration of Aluminum hydroxide can be increased when it is combined with Paricalcitol.
AtazanavirThe serum concentration of Paricalcitol can be increased when it is combined with Atazanavir.
BoceprevirThe serum concentration of Paricalcitol can be increased when it is combined with Boceprevir.
CeritinibThe serum concentration of Paricalcitol can be increased when it is combined with Ceritinib.
ClarithromycinThe serum concentration of Paricalcitol can be increased when it is combined with Clarithromycin.
CobicistatThe serum concentration of Paricalcitol can be increased when it is combined with Cobicistat.
ColesevelamThe serum concentration of Paricalcitol can be decreased when it is combined with Colesevelam.
DanazolDanazol may increase the hypercalcemic activities of Paricalcitol.
DarunavirThe serum concentration of Paricalcitol can be increased when it is combined with Darunavir.
DigoxinThe risk or severity of adverse effects can be increased when Paricalcitol is combined with Digoxin.
DihydrotachysterolThe risk or severity of adverse effects can be increased when Dihydrotachysterol is combined with Paricalcitol.
IdelalisibThe serum concentration of Paricalcitol can be increased when it is combined with Idelalisib.
IndinavirThe serum concentration of Paricalcitol can be increased when it is combined with Indinavir.
ItraconazoleThe serum concentration of Paricalcitol can be increased when it is combined with Itraconazole.
KetoconazoleThe serum concentration of Paricalcitol can be increased when it is combined with Ketoconazole.
Mineral oilThe serum concentration of Paricalcitol can be decreased when it is combined with Mineral oil.
NefazodoneThe serum concentration of Paricalcitol can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Paricalcitol can be increased when it is combined with Nelfinavir.
OrlistatThe serum concentration of Paricalcitol can be decreased when it is combined with Orlistat.
PosaconazoleThe serum concentration of Paricalcitol can be increased when it is combined with Posaconazole.
RitonavirThe serum concentration of Paricalcitol can be increased when it is combined with Ritonavir.
SaquinavirThe serum concentration of Paricalcitol can be increased when it is combined with Saquinavir.
SucralfateThe serum concentration of Sucralfate can be increased when it is combined with Paricalcitol.
TelaprevirThe serum concentration of Paricalcitol can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Paricalcitol can be increased when it is combined with Telithromycin.
TrichlormethiazideTrichlormethiazide may increase the hypercalcemic activities of Paricalcitol.
VoriconazoleThe serum concentration of Paricalcitol can be increased when it is combined with Voriconazole.
Food InteractionsNot Available

Targets

1. Vitamin D3 receptor

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Vitamin D3 receptor P11473 Details

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
  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
  3. Andress DL: Vitamin D treatment in chronic kidney disease. Semin Dial. 2005 Jul-Aug;18(4):315-21. Pubmed
  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. Epub 2009 Jun 3. Pubmed
  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. Epub 2010 Mar 2. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes

1. 1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial Q07973 Details

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
  2. Abbott Laboratories. Zemplar® (paricalcitol) capsules prescribing information. North Chicago, IL; 2010 June.

2. Cytochrome P450 3A4

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Abbott Laboratories. Zemplar® (paricalcitol) capsules prescribing information. North Chicago, IL; 2010 June.

3. UDP-glucuronosyltransferase 1-4

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
UDP-glucuronosyltransferase 1-4 P22310 Details

References:

  1. Abbott Laboratories. Zemplar® (paricalcitol) capsules prescribing information. North Chicago, IL; 2010 June.

Comments
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12