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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
SynonymLanguageCode
19-Nor-1alpha,25-dihydroxyvitamin D2Not AvailableNot Available
ParicalcitolNot AvailableNot Available
ZemplarNot AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Zemplarinjection, solution5 ug/mLintravenousAbb Vie Inc.1998-04-17Not AvailableUs
Zemplarcapsule, liquid filled2 ugoralAbb Vie Inc.2010-06-14Not AvailableUs
Zemplarcapsule, liquid filled4 ugoralAbb Vie Inc.2010-06-14Not AvailableUs
Zemplarcapsule, liquid filled1 ugoralAbb Vie Inc.2010-06-14Not AvailableUs
Zemplarinjection, solution2 ug/mLintravenousAbb Vie Inc.1998-04-17Not AvailableUs
Paricalcitolinjection, solution2 ug/mLintravenousHospira, Inc.2014-11-01Not AvailableUs
Paricalcitolinjection, solution5 ug/mLintravenousHospira, Inc.2014-11-01Not AvailableUs
Zemplarcapsule, liquid filled1 ugoralCardinal Health2005-05-26Not AvailableUs
Paricalcitolcapsule, liquid filled1 ugoralZydus Pharmaceuticals USA Inc2010-06-14Not AvailableUs
Paricalcitolcapsule, liquid filled2 ugoralZydus Pharmaceuticals USA Inc2010-06-14Not AvailableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Paricalcitolcapsule, liquid filled1 ugoralTeva Pharmaceuticals USA Inc2013-09-30Not AvailableUs
Paricalcitolcapsule, liquid filled2 ugoralTeva Pharmaceuticals USA Inc2013-09-30Not AvailableUs
Paricalcitolcapsule, liquid filled4 ugoralTeva Pharmaceuticals USA Inc2013-09-30Not AvailableUs
Paricalcitolcapsule, liquid filled1 ugoralBanner Pharmacaps2014-03-27Not AvailableUs
Paricalcitolcapsule, liquid filled2 ugoralBanner Pharmacaps2014-03-27Not AvailableUs
Paricalcitolcapsule, liquid filled4 ugoralBanner Pharmacaps2014-03-27Not AvailableUs
Paricalcitolcapsule, liquid filled1 ugoralDr. Reddy's Laboratories Limited2014-06-25Not AvailableUs
Paricalcitolcapsule, liquid filled2 ugoralDr. Reddy's Laboratories Limited2014-06-25Not AvailableUs
Paricalcitolcapsule, liquid filled4 ugoralDr. Reddy's Laboratories Limited2014-06-25Not AvailableUs
Paricalcitolcapsule, liquid filled1 ugoralGolden State Medical Supply, Inc.2014-04-23Not AvailableUs
Paricalcitolcapsule, liquid filled2 ugoralGolden State Medical Supply, Inc.2014-04-23Not AvailableUs
Paricalcitolcapsule, liquid filled4 ugoralGolden State Medical Supply, Inc.2014-03-27Not AvailableUs
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 KeyBPKAHTKRCLCHEA-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 substrateNon-inhibitor0.8277
CYP450 2D6 substrateNon-inhibitor0.948
CYP450 2C19 substrateNon-inhibitor0.8491
CYP450 3A4 substrateNon-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
Pharmacoeconomics
Manufacturers
  • Abbott laboratories pharmaceutical products div
  • Abbott laboratories
Packagers
Dosage forms
FormRouteStrength
Capsule, liquid filledoral1 ug
Capsule, liquid filledoral2 ug
Capsule, liquid filledoral4 ug
Injection, solutionintravenous2 ug/mL
Injection, solutionintravenous5 ug/mL
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 ReferenceNot Available
External Links
ATC CodesH05BX02
AHFS Codes
  • 88:16.00
PDB EntriesNot Available
FDA labelDownload (447 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
CholecalciferolVitamin D analogs may enhance the adverse/toxic effect of other Vitamin D analogs. Avoid combined use of multiple vitamin D analogs (at pharmacologic doses). Prescribing information for calcitriol, doxercalciferol, paricalcitol, and alfacalcidol each specifically cautions against such combined use. Though not specified in the prescribing information for calcipotriene, cholecalciferol, and ergocalciferol, each contains warnings regarding the potential for vitamin D toxicity.
ColesevelamBile acid sequestrants such as colesevelam may decrease the serum concentration of Vitamin D Analogs. More specifically, bile acid sequestrants may impair absorption of Vitamin D Analogs. Avoid concomitant administration of vitamin D analogs and bile acid sequestrants (e.g., cholestyramine). Monitor plasma calcium concentrations in patients receiving combined therapy with these agents. This is particularly important in patients receiving higher doses of a bile acid sequestant (i.e., 30 g/day or more of cholestyramine or equivalent) or in patients experiencing bile acid sequestrant-induced steatorrhea. Specific recommendations regarding the separation of administration of these agents are not defined; however, it would seem prudent to separate the administration of these agents by several hours to minimize the potential risk of interaction. Similar precautions do not apply to parenterally administered vitamin D analogs.
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.

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