Details of the Drug

General Information of Drug (ID: DM1XHYJ)

• Drug Name: Etidronic acid
• Synonyms: EHDP; Etidronate; Etidronsaeure; HEDP; Osteoscan; Acetodiphosphonic acid; Acide etidronique; Acido etidronico; Acidumetidronicum; Didronel IV; Etidronic acid monohydrate; Hydroxyethanediphosphonic acid; Oxyethylidenediphosphonic acid; Turpinal SL; Dequest2010; Dequest 2015; Dequest Z 010; Ferrofos 510; RP 61; Acide etidronique [INN-French]; Acido etidronico [INN-Spanish]; Acidum etidronicum [INN-Latin]; Diphosphonate (base); Etidronic acid (USAN/INN); Etidronic acid [USAN:INN:BAN]; Hydroxyethane-1,1-diphosphonic acid; Ethane-1-hydroxy-1,1-bisphosphonate; Ethane-1-hydroxy-1,1-bisphosphonic acid; Ethane-1-hydroxy-1,1-diphosphonate; Ethane-1-hydroxy-1,1-diphosphonic acid; Phosphonic acid, 1-hydroxy-1,1-ethanediyl ester; (1-Hydroxyethylene)diphosphonic acid; (1-Hydroxyethylidene)bis(phosphonic acid); (1-Hydroxyethylidene)bisphosphonic acid; (1-Hydroxyethylidene)diphoshonic acid; (1-Hydroxyethylidene)diphosphonic acid; (1-hydroxy-1-phosphonoethyl)phosphonic acid; (1-hydroxyethane-1,1-diyl)bis(phosphonic acid); (Hydroxyethylidene)diphosphonic acid; 1,1,1-Ethanetriol diphosphonate; 1-HYDROXY-1,1-DIPHOSPHONOETHANE; 1-Hydroxyethane-1,1,-diphosphonic acid; 1-Hydroxyethane-1,1-bisphosphonic acid; 1-Hydroxyethane-1,1-diphosphonate; 1-Hydroxyethane-1,1-diphosphonic acid; 1-Hydroxyethanediphosphonic acid; 1-Hydroxyethylidene 1,1-diphosphonic acid; 1-Hydroxyethylidene-1,1-biphosphonate; 1-Hydroxyethylidene-1,1-bisphosphonate; 1-Hydroxyethylidene-1,1-diphosphonic acid; 1-Hydroxyethylidenediphosphonic acid; 1000SL

Indication

Disease Entry	ICD 11	Status	REF
Bone Paget disease	N.A.	Approved	[1]
Paget's disease	FB85	Approved	[2]

• Therapeutic Class: Bone Density Conservation Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 206.03
  Logarithm of the Partition Coefficient (xlogp); -3.7
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 5
  Hydrogen Bond Acceptor Count (hbondacc); 7
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
  Bioavailability: The bioavailability of drug is 1-10% [1]
  Clearance: The renal clearance of drug is 0.09 L/h/kg [1]
  Elimination: 50% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 1 - 6 hours [1]
  Metabolism: The drug is not metabolised []
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 97.07349 micromolar/kg/day [4]
  Vd: The volume of distribution (Vd) of drug is 0.3-1.3 L/kg [1]
• Chemical Identifiers:
  Formula: C2H8O7P2
  IUPAC Name: (1-hydroxy-1-phosphonoethyl)phosphonic acid
  Canonical SMILES: CC(O)(P(=O)(O)O)P(=O)(O)O
  InChI: InChI=1S/C2H8O7P2/c1-2(3,10(4,5)6)11(7,8)9/h3H,1H3,(H2,4,5,6)(H2,7,8,9)
  InChIKey: DBVJJBKOTRCVKF-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 3305
  ChEBI ID: CHEBI:4907
  CAS Number: 2809-21-4
  DrugBank ID: DB01077
  TTD ID: D00NNC
  ACDINA ID: D00256
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Protein-tyrosine phosphatase sigma (R-PTP-sigma)	TTCWXFA	PTPRS_HUMAN	Inhibitor	[5]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Gene/Protein Processing	[6]

Molecular Expression Atlas of This Drug

• The Studied Disease: Bone Paget disease

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Protein-tyrosine phosphatase sigma (R-PTP-sigma)	DTT	PTPRS	1.17E-01	0.21	0.65

Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Decreased renal excretion of Etidronic acid caused by Remdesivir mediated nephrotoxicity.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[7]
Inotersen	DMJ93CT	Major	Increased risk of nephrotoxicity by the combination of Etidronic acid and Inotersen.	Amyloidosis [5D00]	[7]
Kanamycin	DM2DMPO	Moderate	Increased risk of hypocalcemia by the combination of Etidronic acid and Kanamycin.	Bacterial infection [1A00-1C4Z]	[8]
Streptomycin	DME1LQN	Moderate	Increased risk of hypocalcemia by the combination of Etidronic acid and Streptomycin.	Bacterial infection [1A00-1C4Z]	[8]
Iodipamide	DMXIQYS	Major	Increased risk of nephrotoxicity by the combination of Etidronic acid and Iodipamide.	Cholelithiasis [DC11]	[9]
177Lu-DOTATATE	DMT8GVU	Moderate	Increased risk of nephrotoxicity by the combination of Etidronic acid and 177Lu-DOTATATE.	Hepatitis virus infection [1E50-1E51]	[8]
Etelcalcetide	DMHP9BL	Major	Increased risk of hypocalcemia by the combination of Etidronic acid and Etelcalcetide.	Hyper-parathyroidism [5A51]	[7]
Givosiran	DM5PFIJ	Moderate	Increased risk of nephrotoxicity by the combination of Etidronic acid and Givosiran.	Inborn porphyrin/heme metabolism error [5C58]	[8]
Iron	DMAP8MV	Moderate	Decreased absorption of Etidronic acid due to formation of complexes caused by Iron.	Iron deficiency anaemia [3A00]	[10]
Moxetumomab pasudotox	DMN63DZ	Moderate	Increased risk of nephrotoxicity by the combination of Etidronic acid and Moxetumomab pasudotox.	Mature B-cell leukaemia [2A82]	[8]
Exjade	DMHPRWG	Major	Increased risk of GI mucosal injury/bleeding risk by the combination of Etidronic acid and Exjade.	Mineral absorption/transport disorder [5C64]	[11]
Lanthanum carbonate	DMMJQSH	Moderate	Decreased absorption of Etidronic acid due to formation of complexes caused by Lanthanum carbonate.	Mineral absorption/transport disorder [5C64]	[12]
Gallium nitrate	DMF9O6B	Moderate	Increased risk of nephrotoxicity by the combination of Etidronic acid and Gallium nitrate.	Mineral excesses [5B91]	[8]
Choline salicylate	DM8P137	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Etidronic acid and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[13]
Temsirolimus	DMS104F	Moderate	Increased risk of nephrotoxicity by the combination of Etidronic acid and Temsirolimus.	Renal cell carcinoma [2C90]	[8]
Colistimethate	DMZ9BMU	Moderate	Increased risk of nephrotoxicity by the combination of Etidronic acid and Colistimethate.	Respiratory infection [CA07-CA4Z]	[8]
Salsalate	DM13P4C	Moderate	Increased risk of nephrotoxicity by the combination of Etidronic acid and Salsalate.	Rheumatoid arthritis [FA20]	[13]
Telavancin	DM58VQX	Moderate	Increased risk of nephrotoxicity by the combination of Etidronic acid and Telavancin.	Staphylococcal/streptococcal disease [1B5Y]	[8]
Lenvatinib	DMB1IU4	Moderate	Increased risk of nephrotoxicity by the combination of Etidronic acid and Lenvatinib.	Thyroid cancer [2D10]	[8]
Olsalazine	DMZW9HA	Moderate	Increased risk of nephrotoxicity by the combination of Etidronic acid and Olsalazine.	Ulcerative colitis [DD71]	[8]
Plazomicin	DMKMBES	Moderate	Increased risk of hypocalcemia by the combination of Etidronic acid and Plazomicin.	Urinary tract infection [GC08]	[8]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Magnesium stearate	E00208	11177	lubricant

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Etidronic acid 200 mg tablet	200 mg	Oral Tablet	Oral
Etidronic acid 400 mg tablet	400 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] Etidronic acid. A review of its pharmacological properties and therapeutic efficacy in resorptive bone disease. Drugs Aging. 1994 Dec;5(6):446-74. doi: 10.2165/00002512-199405060-00006.
• [2] 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: 7184).
• [3] BDDCS applied to over 900 drugs
• [4] 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
• [5] Human protein tyrosine phosphatase-sigma: alternative splicing and inhibition by bisphosphonates. J Bone Miner Res. 1996 Apr;11(4):535-43.
• [6] Screening of a chemical library reveals novel PXR-activating pharmacologic compounds. Toxicol Lett. 2015 Jan 5;232(1):193-202. doi: 10.1016/j.toxlet.2014.10.009. Epub 2014 Oct 16.
• [7] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [8] Chang JT, Green L, Beitz J "Renal failure with the use of zoledronic acid." N Engl J Med 349 (2003): 1676-9 discussion 1676-9. [PMID: 14573746]
• [9] Bentley ML, Corwin HL, Dasta J "Drug-induced acute kidney injury in the critically ill adult: recognition and prevention strategies." Crit Care Med 38(6 Suppl) (2010): S169-74. [PMID: 20502171]
• [10] Product Information. Boniva (ibandronate). Roche Laboratories, Nutley, NJ.
• [11] Product Information. Exjade (deferasirox). Novartis Pharmaceuticals, East Hanover, NJ.
• [12] Canadian Pharmacists Association.
• [13] Product Information. Actonel (risedronate). Procter and Gamble Pharmaceuticals, Cincinnati, OH.