Details of the Drug

General Information of Drug (ID: DM8ZVJ7)

Drug Name

Calcitriol

Synonyms

calcitriol; Rocaltrol; 32222-06-3; Calcijex; Topitriol; 1alpha,25-Dihydroxyvitamin D3; Silkis; Soltriol; 1alpha,25-Dihydroxycholecalciferol; Calcitriolum; Dihydroxyvitamin D3; 1,25-DHCC; 1,25-Dihydroxyvitamin D; Vectical; 1,25-DIHYDROXYCHOLECALCIFEROL; 1,25-Dihydroxyvitamin D3; 1alpha,25-Dihydroxyvitamin D; 1-alpha,25-Dihydroxyvitamin D3; Calcitriolum [INN-Latin]; UNII-FXC9231JVH; 1alpha,25(OH)2D3; DN-101; 1,25-Dihydroxycholecaliferol; CCRIS 5522; Ro 21-5535; HSDB 3482; 1-alpha,25-Dihydroxycholecalciferol; EINECS 250-963-8; DN 101; Calcitriol (chemotherapy-induced alopecia); Calcitriol (chemotherapy-induced alopecia), Cytotech Labs; Calcitriol (API-31543, drug-induced alopecia), Cytotech Labs; 1alpha,25 dihydroxyvitamin D(3)

Indication

Disease Entry	ICD 11	Status	REF
Congenital alopecia	LC30	Approved	[1]
Hypoparathyroidism	5A50	Approved	[2]
Hypophosphatemia	N.A.	Approved	[2]
Renal osteodystrophy	N.A.	Approved	[2]
Rickets	5B57	Approved	[2]
Autosomal dominant hypocalcemia	5A50.0Y	Investigative	[2]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

416.6

Logarithm of the Partition Coefficient (xlogp)

5.1

Rotatable Bond Count (rotbonds)

6

Hydrogen Bond Donor Count (hbonddonor)

3

Hydrogen Bond Acceptor Count (hbondacc)

3

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
Bioavailability: 61% of drug becomes completely available to its intended biological destination(s) [4]
Clearance: The clearance of drug is 23.5 +/- 4.34 mL/min [5]
Elimination: In normal subjects, approximately 27% and 7% of the radioactivity appeared in the feces and urine, respectively, within 24 hours []
Half-life: The concentration or amount of drug in body reduced by one-half in 5 - 8 hours []
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.000103 micromolar/kg/day [6]
Vd: The volume of distribution (Vd) of drug is 0.49 +/- 0.14 L/kg [5]

Chemical Identifiers

Formula: C27H44O3
IUPAC Name: (1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol
Canonical SMILES: C[C@H](CCCC(C)(C)O)[C@H]1CC[C@@H]\\2[C@@]1(CCC/C2=C\\C=C/3\\C[C@H](C[C@@H](C3=C)O)O)C
InChI: InChI=1S/C27H44O3/c1-18(8-6-14-26(3,4)30)23-12-13-24-20(9-7-15-27(23,24)5)10-11-21-16-22(28)17-25(29)19(21)2/h10-11,18,22-25,28-30H,2,6-9,12-17H2,1,3-5H3/b20-10+,21-11-/t18-,22-,23-,24+,25+,27-/m1/s1
InChIKey: GMRQFYUYWCNGIN-NKMMMXOESA-N

Cross-matching ID

PubChem CID: 5280453
ChEBI ID: CHEBI:17823
CAS Number: 32222-06-3
DrugBank ID: DB00136
TTD ID: D0T2PL
INTEDE ID: DR0260
ACDINA ID: D00090

Repurposed Drugs (RPD)

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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-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[8]
Vitamin D(3) 24-hydroxylase (CYP24A1)	DEFI12S	CP24A_HUMAN	Substrate	[9]
UDP-glucuronosyltransferase 1A4 (UGT1A4)	DELOY3P	UD14_HUMAN	Substrate	[10]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1)	OTG2T749	CP24A_HUMAN	Gene/Protein Processing	[11]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 (PLCB4)	OTPA0QHW	PLCB4_HUMAN	Gene/Protein Processing	[12]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 (PLCD3)	OTB22A4J	PLCD3_HUMAN	Gene/Protein Processing	[13]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1 (PLCH1)	OT6Z1L2E	PLCH1_HUMAN	Gene/Protein Processing	[13]
10 kDa heat shock protein, mitochondrial (HSPE1)	OT7JSZLB	CH10_HUMAN	Gene/Protein Processing	[14]
11-beta-hydroxysteroid dehydrogenase 1 (HSD11B1)	OTO7FJA9	DHI1_HUMAN	Gene/Protein Processing	[15]
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2)	OTHF4H9U	DHI2_HUMAN	Gene/Protein Processing	[13]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Gene/Protein Processing	[12]
15-hydroxyprostaglandin dehydrogenase (HPGD)	OTYZI6JB	PGDH_HUMAN	Gene/Protein Processing	[13]
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2)	OT3K7HY5	DHB2_HUMAN	Gene/Protein Processing	[16]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Congenital alopecia

ICD Disease Classification

LC30

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
Vitamin D(3) 24-hydroxylase (CYP24A1)	DME	CYP24A1	7.29E-01	1.85E-01	9.48E-02
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.10E-01	-1.23E-01	-2.88E-01

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 Calcitriol (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Magnesium Sulfate	DMVEK07	Moderate	Increased risk of hypermagnesemia by the combination of Calcitriol and Magnesium Sulfate.	Acute pain [MG31]	[17]
Butalbital	DM9J04X	Moderate	Increased metabolism of Calcitriol caused by Butalbital mediated induction of CYP450 enzyme.	Anxiety disorder [6B00-6B0Z]	[17]
Methylphenobarbital	DMDSWAG	Moderate	Increased metabolism of Calcitriol caused by Methylphenobarbital mediated induction of CYP450 enzyme.	Anxiety disorder [6B00-6B0Z]	[17]
Secobarbital	DM14RF5	Moderate	Increased metabolism of Calcitriol caused by Secobarbital mediated induction of CYP450 enzyme.	Chronic insomnia [7A00]	[17]
Primidone	DM0WX6I	Moderate	Increased metabolism of Calcitriol caused by Primidone mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[17]
Felbamate	DM1V5ZS	Moderate	Increased metabolism of Calcitriol caused by Felbamate mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[17]
Oxcarbazepine	DM5PU6O	Moderate	Increased metabolism of Calcitriol caused by Oxcarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[17]
Phenytoin	DMNOKBV	Moderate	Increased metabolism of Calcitriol caused by Phenytoin mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[17]
Fosphenytoin	DMOX3LB	Moderate	Increased metabolism of Calcitriol caused by Fosphenytoin mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[17]
Rufinamide	DMWE60C	Moderate	Increased metabolism of Calcitriol caused by Rufinamide mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[17]
Phenobarbital	DMXZOCG	Moderate	Increased metabolism of Calcitriol caused by Phenobarbital mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[17]
Carbamazepine	DMZOLBI	Moderate	Increased metabolism of Calcitriol caused by Carbamazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[17]
Isoniazid	DM5JVS3	Moderate	Increased metabolism of Calcitriol caused by Isoniazid mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[17]
Rifampin	DMA8J1G	Moderate	Increased metabolism of Calcitriol caused by Rifampin mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[17]
Rifapentine	DMCHV4I	Moderate	Increased metabolism of Calcitriol caused by Rifapentine mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[17]
Amobarbital	DM0GQ8N	Moderate	Increased metabolism of Calcitriol caused by Amobarbital mediated induction of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[17]
Butabarbital	DMC5AST	Moderate	Increased metabolism of Calcitriol caused by Butabarbital mediated induction of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[17]
Pentobarbital	DMFNH7L	Moderate	Increased metabolism of Calcitriol caused by Pentobarbital mediated induction of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[17]
Orlistat	DMRJSP8	Minor	Decreased absorption of Calcitriol caused by Orlistat.	Obesity [5B80-5B81]	[18]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Allura red AC dye	E00338	33258	Colorant
Butylated hydroxytoluene	E00336	31404	Antioxidant
Hydrazine yellow	E00409	164825	Colorant
Isopropyl alcohol	E00070	3776	Antimicrobial preservative; Solvent
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
methylparaben	E00149	7456	Antimicrobial preservative
Propyl 4-hydroxybenzoate	E00141	7175	Antimicrobial preservative
Propylparaben sodium	E00567	23679044	Antimicrobial preservative
Sodium methylparaben	E00543	23663626	Antimicrobial preservative
Sunset yellow FCF	E00255	17730	Colorant
Ammonia	E00007	222	Alkalizing agent
Butylhydroxyanisole	E00308	24667	Antimicrobial preservative; Antioxidant
Eisenoxyd	E00585	56841934	Colorant
FD&C red no. 3	E00629	Not Available	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
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
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
Calcitriol 0.00025 mg capsule	0.00025 mg	Oral Capsule	Oral
Calcitriol 0.0005 mg capsule	0.0005 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: 2779).
2	Calcitriol FDA Label
3	BDDCS applied to over 900 drugs
4	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
5	Brandi L, Egfjord M, Olgaard K: Pharmacokinetics of 1,25(OH)2D3 and 1(OH)D3 in normal and uraemic men Nephrology Dialysis Transplantation. 2002 May 1;17(5):829C842.
6	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
7	Kaposi sarcoma is a therapeutic target for vitamin D(3) receptor agonist. Blood. 2000 Nov 1;96(9):3188-94.
8	Intestinal and hepatic CYP3A4 catalyze hydroxylation of 1alpha,25-dihydroxyvitamin D(3): implications for drug-induced osteomalacia. Mol Pharmacol. 2006 Jan;69(1):56-65.
9	The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer. 2014 May;14(5):342-57.
10	Identification of human UDP-glucuronosyltransferases catalyzing hepatic 1alpha,25-dihydroxyvitamin D3 conjugation. Biochem Pharmacol. 2008 Mar 1;75(5):1240-50.
11	DNA microarray analysis of vitamin D-induced gene expression in a human colon carcinoma cell line. Physiol Genomics. 2004 Apr 13;17(2):122-9. doi: 10.1152/physiolgenomics.00002.2003.
12	Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
13	Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
14	Comparison of the gene expression profiles of monocytic versus granulocytic lineages of HL-60 leukemia cell differentiation by DNA microarray analysis. Life Sci. 2003 Aug 15;73(13):1705-19. doi: 10.1016/s0024-3205(03)00515-0.
15	Role of calcitriol and cortisol on human adipocyte proliferation and oxidative and inflammatory stress: a microarray study. J Nutrigenet Nutrigenomics. 2008;1(1-2):30-48. doi: 10.1159/000109873. Epub 2007 Oct 16.
16	Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
17	Product Information. Hectorol (doxercalciferol). Genzyme Corporation, Cambridge, MA.
18	Product Information. Xenical (orlistat). Roche Laboratories, Nutley, NJ.