Details of the Drug

General Information of Drug (ID: DMYBV3G)

Drug Name

Paricalcitol

Synonyms

Paracalcin; Zemplar; Abbott brand of paricalcitol; Paricalcitol [USAN]; Ab 122358; ABT-358; Zemplar (TN); Paricalcitol (USAN/INN); Paricalcitol, 19-nor-(OH)2-vitD2, paracalcin; (1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R,5S)-6-hydroxy-5,6-dimethylhept-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]cyclohexane-1,3-diol; (1R,3R,7E)-17beta-[(2R,3E,5S)-6-hydroxy-5,6-dimethylhept-3-en-2-yl]-9,10-secoestra-5,7-diene-1,3-diol; (1alpha.3beta,7E,22E)-19-Nor-9,10-secoergosta-5,7,22-triene-1,3,25-triol; (7E,22E)-19-Nor-9,10-secoergosta-5,7,22-triene-1alpha,3beta,25-triol; 19-Nor-1,25-(OH)2D2; 19-Nor-1-alpha,25-dihydroxyvitamin D2; 19-Nor-1alpha,25-dihydroxyvitamin D2; 19-Nor-9,10-secoergosta-5,7,22-triene-1,3,25-triol,(1alpha,3beta,7E,22E)

Indication

Disease Entry	ICD 11	Status	REF
Hyperparathyroidism	5A51	Approved	[1]
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Therapeutic Class

Parasympathomimetics

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

416.6

Logarithm of the Partition Coefficient (xlogp)

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption: The drug is well absorbed []
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
Bioavailability: 72% of drug becomes completely available to its intended biological destination(s) [3]
Clearance: The drug present in the plasma can be removed from the body at the rate of 0.89 mL/min/kg [4]
Elimination: 0% of drug is excreted from urine in the unchanged form [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 4 - 6 hours [4]
Metabolism: The drug is metabolized via the multiple hepatic and non-hepatic enzymes, including mitochondrial CYP24, as well as CYP3A4 and UGT1A4 []
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.000103 micromolar/kg/day [5]
Unbound Fraction: The unbound fraction of drug in plasma is 0.0016% [4]
Vd: The volume of distribution (Vd) of drug is 30.8 +/- 7.5 L []

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Electrolyte imbalance	Not Available	CCKBR	OTQSNXOI	[6]
Iron and trace metal metabolism disorders	Not Available	PTH1R	OTQF5ZAK	[6]
Iron and trace metal metabolism disorders	Not Available	ALPP	OTZU4G9W	[6]
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Chemical Identifiers

Formula: C27H44O3
IUPAC Name: (1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R,5S)-6-hydroxy-5,6-dimethylhept-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]cyclohexane-1,3-diol
Canonical SMILES: C[C@H](/C=C/[C@H](C)C(C)(C)O)[C@H]1CC[C@@H]\\2[C@@]1(CCC/C2=C\\C=C3C[C@H](C[C@@H](C3)O)O)C
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
InChIKey: BPKAHTKRCLCHEA-UBFJEZKGSA-N

Cross-matching ID

PubChem CID: 5281104
ChEBI ID: CHEBI:7931
CAS Number: 131918-61-1
DrugBank ID: DB00910
TTD ID: D0N1TP
ACDINA ID: D00509

Combinatorial Drugs (CBD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Vitamin D3 receptor (VDR)	TTK59TV	VDR_HUMAN	Agonist	[7]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Alkaline phosphatase, placental type (ALPP)	OTZU4G9W	PPB1_HUMAN	Drug Response	[6]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Gene/Protein Processing	[8]
Gastrin/cholecystokinin type B receptor (CCKBR)	OTQSNXOI	GASR_HUMAN	Drug Response	[6]
Integrin alpha-M (ITGAM)	OTAG6HWU	ITAM_HUMAN	Gene/Protein Processing	[9]
Monocyte differentiation antigen CD14 (CD14)	OT83GJ47	CD14_HUMAN	Gene/Protein Processing	[9]
Parathyroid hormone (PTH)	OTD721UF	PTHY_HUMAN	Gene/Protein Processing	[10]
Parathyroid hormone/parathyroid hormone-related peptide receptor (PTH1R)	OTQF5ZAK	PTH1R_HUMAN	Drug Response	[6]
Vitamin D3 receptor	OTFC7K35	VDR_HUMAN	Protein Interaction/Cellular Processes	[11]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Hyperparathyroidism

ICD Disease Classification

5A51

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Vitamin D3 receptor (VDR)	DTT	VDR	1.69E-02	-0.23	-0.66

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Paricalcitol (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Arn-509	DMT81LZ	Moderate	Increased metabolism of Paricalcitol caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[12]
Posaconazole	DMUL5EW	Moderate	Decreased metabolism of Paricalcitol caused by Posaconazole mediated inhibition of CYP450 enzyme.	Aspergillosis [1F20]	[12]
Clarithromycin	DM4M1SG	Moderate	Decreased metabolism of Paricalcitol caused by Clarithromycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[12]
Troleandomycin	DMUZNIG	Moderate	Decreased metabolism of Paricalcitol caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[12]
Telithromycin	DMZ4P3A	Moderate	Decreased metabolism of Paricalcitol caused by Telithromycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[12]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Paricalcitol caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[13]
Tucatinib	DMBESUA	Moderate	Decreased metabolism of Paricalcitol caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[12]
Nefazodone	DM4ZS8M	Moderate	Decreased metabolism of Paricalcitol caused by Nefazodone mediated inhibition of CYP450 enzyme.	Depression [6A70-6A7Z]	[12]
Felbamate	DM1V5ZS	Moderate	Increased metabolism of Paricalcitol caused by Felbamate mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[14]
Stiripentol	DMMSDOY	Moderate	Decreased metabolism of Paricalcitol caused by Stiripentol mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[12]
Fosphenytoin	DMOX3LB	Moderate	Increased metabolism of Paricalcitol caused by Fosphenytoin mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[14]
Rufinamide	DMWE60C	Moderate	Increased metabolism of Paricalcitol caused by Rufinamide mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[14]
Phenobarbital	DMXZOCG	Moderate	Increased metabolism of Paricalcitol caused by Phenobarbital mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[14]
Itraconazole	DMCR1MV	Moderate	Decreased metabolism of Paricalcitol caused by Itraconazole mediated inhibition of CYP450 enzyme.	Fungal infection [1F29-1F2F]	[12]
Miconazole	DMPMYE8	Moderate	Decreased metabolism of Paricalcitol caused by Miconazole mediated inhibition of CYP450 enzyme.	Fungal infection [1F29-1F2F]	[12]
Ketoconazole	DMPZI3Q	Moderate	Decreased metabolism of Paricalcitol caused by Ketoconazole mediated inhibition of CYP450 enzyme.	Fungal infection [1F29-1F2F]	[12]
Isoniazid	DM5JVS3	Moderate	Increased metabolism of Paricalcitol caused by Isoniazid mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[14]
Rifampin	DMA8J1G	Moderate	Increased metabolism of Paricalcitol caused by Rifampin mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[14]
Rifapentine	DMCHV4I	Moderate	Increased metabolism of Paricalcitol caused by Rifapentine mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[14]
Fosamprenavir	DM4W9B3	Moderate	Decreased metabolism of Paricalcitol caused by Fosamprenavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[12]
Cobicistat	DM6L4H2	Moderate	Decreased metabolism of Paricalcitol caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[12]
Atazanavir	DMSYRBX	Moderate	Decreased metabolism of Paricalcitol caused by Atazanavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[12]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Paricalcitol caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[15]
Amobarbital	DM0GQ8N	Moderate	Increased metabolism of Paricalcitol caused by Amobarbital mediated induction of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[14]
Ceritinib	DMB920Z	Moderate	Decreased metabolism of Paricalcitol caused by Ceritinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[12]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Paricalcitol caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[16]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of Paricalcitol caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[17]
Idelalisib	DM602WT	Moderate	Decreased metabolism of Paricalcitol caused by Idelalisib mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[12]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Paricalcitol caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[18]
Dabrafenib	DMX6OE3	Moderate	Increased metabolism of Paricalcitol caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[12]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Paricalcitol caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[12]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Paricalcitol caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[19]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Paricalcitol caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[20]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Paricalcitol caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[21]
Lonafarnib	DMGM2Z6	Moderate	Decreased metabolism of Paricalcitol caused by Lonafarnib mediated inhibition of CYP450 enzyme.	Premature ageing appearance [LD2B]	[12]
Enzalutamide	DMGL19D	Moderate	Increased metabolism of Paricalcitol caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[22]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Paricalcitol caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[12]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Paricalcitol caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[23]
LEE011	DMMX75K	Moderate	Decreased metabolism of Paricalcitol caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[24]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Paricalcitol caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[25]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Butylated hydroxytoluene	E00336	31404	Antioxidant
FD&C blue no. 1	E00263	19700	Colorant
Isopropyl alcohol	E00070	3776	Antimicrobial preservative; Solvent
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Sunset yellow FCF	E00255	17730	Colorant
Ammonia	E00007	222	Alkalizing agent
Butyl alcohol	E00011	263	Flavoring agent; Solvent
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Glycerin	E00026	753	Antimicrobial preservative; Emollient; Flavoring agent; Humectant; Lubricant; Plasticizing agent; Solvent; Suppository base; Tonicity agent; Viscosity-controlling agent
Hexahydric alcohol	E00083	5780	Diluent; Flavoring agent; Humectant; Plasticizing agent
Medium-chain triglyceride	E00640	Not Available	Emollient; Lubricant; Surfactant
Polyoxyl 35 castor oil	E00660	Not Available	Emulsifying agent; Solubilizing agent; Surfactant
Polysorbate 80	E00665	Not Available	Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Soybean lecithin	E00637	Not Available	Other agent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Water	E00035	962	Solvent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Paricalcitol 0.002 mg capsule	0.002 mg	Oral Capsule	Oral
Paricalcitol 0.004 mg capsule	0.004 mg	Oral Capsule	Oral
Paricalcitol 0.001 mg capsule	0.001 mg	Oral Capsule	Oral

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References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2791).
2	BDDCS applied to over 900 drugs
3	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6	ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
7	New acquisitions in therapy of secondary hyperparathyroidism in chronic kidney disease and peritoneal dialysis patients: role of vitamin D receptor... Contrib Nephrol. 2009;163:219-226.
8	Transcriptional control of intestinal cytochrome P-4503A by 1alpha,25-dihydroxy vitamin D3. Mol Pharmacol. 2001 Dec;60(6):1399-406.
9	19-nor-1alpha,25-dihydroxyvitamin D(2) (paricalcitol): effects on clonal proliferation, differentiation, and apoptosis in human leukemic cell lines. J Cancer Res Clin Oncol. 2003 Jan;129(1):35-42. doi: 10.1007/s00432-002-0405-7. Epub 2003 Feb 12.
10	Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Kidney Int. 2003 Apr;63(4):1483-90. doi: 10.1046/j.1523-1755.2003.00878.x.
11	Spotlight on paricalcitol in secondary hyperparathyroidism. Treat Endocrinol. 2005;4(3):185-6. doi: 10.2165/00024677-200504030-00007.
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14	Product Information. Hectorol (doxercalciferol). Genzyme Corporation, Cambridge, MA.
15	Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
16	Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
17	Product Information. Retevmo (selpercatinib). Lilly, Eli and Company, Indianapolis, IN.
18	Product Information. Copiktra (duvelisib). Verastem, Inc., Needham, MA.
19	EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
20	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
21	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
22	Benoist G, van Oort I, et al "Drug-drug interaction potential in men treated with enzalutamide: Mind the gap." Br J Clin Pharmacol 0 (2017): epub. [PMID: 28881501]
23	Cerner Multum, Inc. "Australian Product Information.".
24	DSouza DL, Levasseur LM, Nezamis J, Robbins DK, Simms L, Koch KM "Effect of alosetron on the pharmacokinetics of alprazolam." J Clin Pharmacol 41 (2001): 452-4. [PMID: 11304902]
25	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.