Details of the Drug

General Information of Drug (ID: DMIXC7G)

• Drug Name: Zoledronate
• Synonyms: Aclasta; Reclast; ZOL; Zometa; Novartis brand of zoledronic acid; Zoledronic acid; Zometa Concentrate; Bisphosphonate 3; CGP 42446; CGP 42446A; Aclasta (TN); CGP 42'446; CGP-42446; KS-1132; Reclast (TN); Zoledronic acid (INN); Zoledronic acid [USAN:INN]; Zomera (TN); Zometa (Novartis); Zometa (TN); CGP-42'446; Zometa, Zomera, Aclasta and Reclast, Zoledronic Acid; [1-hydroxy-2-(1H-imidazol-1-yl)ethane-1,1-diyl]bis(phosphonic acid); (1-Hydroxy-2-imidazol-1-ylethylidene)diphosphonic acid; (1-hydroxy-2-(1H-imidazol-1-yl)ethylidene)bisphosphonic acid; (1-hydroxy-2-imidazol-1-yl-1-phosphonoethyl)phosphonic acid; (1-hydroxy-2-imidazol-1-yl-phosphonoethyl)phosphonic acid monohydrate; 2-(imidazol-1-yl)-1-hydroxyethane-1,1-diphosphonic acid; 2-(imidazol-1-yl)-1-hydroxyethylidene-1,1-bisphosphonic acid

Indication

Disease Entry	ICD 11	Status	REF
Hypercalcaemia	5B91.0	Approved	[1]

• Therapeutic Class: Bone Density Conservation Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 272.09
  Topological Polar Surface Area (xlogp); -4.3
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 5
  Hydrogen Bond Acceptor Count (hbondacc); 8
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 788 +/- 181 mcgh/L [2]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 370 +/- 78.5 mcg/L [2]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 0.317 +/- 0.014 h [2]
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
  Clearance: The renal clearance of drug is 3.7 +/- 2.0 L/h [4]
  Elimination: The drug is 39 +/- 16% eliminated in the urine as the unmetabolized parent drug [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 146 hours [4]
  Metabolism: The drug is not metabolised [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.0075 micromolar/kg/day [5]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.78% [6]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.6 L/kg [6]
• Chemical Identifiers:
  Formula: C5H10N2O7P2
  IUPAC Name: (1-hydroxy-2-imidazol-1-yl-1-phosphonoethyl)phosphonic acid
  Canonical SMILES: C1=CN(C=N1)CC(O)(P(=O)(O)O)P(=O)(O)O
  InChI: InChI=1S/C5H10N2O7P2/c8-5(15(9,10)11,16(12,13)14)3-7-2-1-6-4-7/h1-2,4,8H,3H2,(H2,9,10,11)(H2,12,13,14)
  InChIKey: XRASPMIURGNCCH-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 68740
  ChEBI ID: CHEBI:46557
  CAS Number: 118072-93-8
  DrugBank ID: DB00399
  TTD ID: D0VM2L
  VARIDT ID: DR01473

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Geranyltranstransferase (FDPS)	TTIKWV4	FPPS_HUMAN	Modulator	[7]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[8]

Molecular Expression Atlas of This Drug

• The Studied Disease: Hypercalcaemia
• ICD Disease Classification: 5B91.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Geranyltranstransferase (FDPS)	DTT	FDPS	7.06E-03	-0.73	-2.57
Multidrug resistance-associated protein 1 (ABCC1)	DTP	MRP1	4.50E-01	2.98E-01	1.00E+00

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Zoledronate

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Gallium nitrate	DMF9O6B	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Gallium nitrate.	Mineral excesses [5B91]	[26]

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Decreased renal excretion of Zoledronate caused by Remdesivir mediated nephrotoxicity.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[27]
Framycetin	DMF8DNE	Moderate	Increased risk of hypocalcemia by the combination of Zoledronate and Framycetin.	Alcoholic liver disease [DB94]	[26]
Inotersen	DMJ93CT	Major	Increased risk of nephrotoxicity by the combination of Zoledronate and Inotersen.	Amyloidosis [5D00]	[28]
Kanamycin	DM2DMPO	Moderate	Increased risk of hypocalcemia by the combination of Zoledronate and Kanamycin.	Bacterial infection [1A00-1C4Z]	[26]
Amikacin	DM5PDRB	Moderate	Increased risk of hypocalcemia by the combination of Zoledronate and Amikacin.	Bacterial infection [1A00-1C4Z]	[26]
Streptomycin	DME1LQN	Moderate	Increased risk of hypocalcemia by the combination of Zoledronate and Streptomycin.	Bacterial infection [1A00-1C4Z]	[26]
Gentamicin	DMKINJO	Moderate	Increased risk of hypocalcemia by the combination of Zoledronate and Gentamicin.	Bacterial infection [1A00-1C4Z]	[26]
Netilmicin	DMRD1QK	Moderate	Increased risk of hypocalcemia by the combination of Zoledronate and Netilmicin.	Bacterial infection [1A00-1C4Z]	[26]
Tobramycin	DMUI0CH	Moderate	Increased risk of hypocalcemia by the combination of Zoledronate and Tobramycin.	Bacterial infection [1A00-1C4Z]	[26]
Iodipamide	DMXIQYS	Major	Increased risk of nephrotoxicity by the combination of Zoledronate and Iodipamide.	Cholelithiasis [DC11]	[29]
Ketoprofen	DMRKXPT	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Ketoprofen.	Chronic pain [MG30]	[28]
Oxaliplatin	DMQNWRD	Moderate	Decreased renal excretion of Zoledronate caused by Oxaliplatin mediated nephrotoxicity.	Colorectal cancer [2B91]	[30]
Methoxyflurane	DML0RAE	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Methoxyflurane.	Corneal disease [9A76-9A78]	[26]
Ethacrynic acid	DM60QMR	Moderate	Increased risk of hypocalcemia by the combination of Zoledronate and Ethacrynic acid.	Essential hypertension [BA00]	[31]
Mefenamic acid	DMK7HFI	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Zoledronate and Mefenamic acid.	Female pelvic pain [GA34]	[28]
Amphotericin B	DMTAJQE	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Amphotericin B.	Fungal infection [1F29-1F2F]	[26]
Furosemide	DMMQ8ZG	Moderate	Increased risk of hypocalcemia by the combination of Zoledronate and Furosemide.	Heart failure [BD10-BD1Z]	[32]
Bumetanide	DMRV7H0	Moderate	Increased risk of hypocalcemia by the combination of Zoledronate and Bumetanide.	Heart failure [BD10-BD1Z]	[32]
177Lu-DOTATATE	DMT8GVU	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and 177Lu-DOTATATE.	Hepatitis virus infection [1E50-1E51]	[26]
Etelcalcetide	DMHP9BL	Major	Increased risk of hypocalcemia by the combination of Zoledronate and Etelcalcetide.	Hyper-parathyroidism [5A51]	[28]
Givosiran	DM5PFIJ	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Givosiran.	Inborn porphyrin/heme metabolism error [5C58]	[26]
Balsalazide	DMO091F	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Balsalazide.	Indeterminate colitis [DD72]	[26]
Meclofenamic acid	DM05FXR	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Zoledronate and Meclofenamic acid.	Inflammatory spondyloarthritis [FA92]	[33]
Methotrexate	DM2TEOL	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Methotrexate.	Leukaemia [2A60-2B33]	[26]
Moxetumomab pasudotox	DMN63DZ	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Moxetumomab pasudotox.	Mature B-cell leukaemia [2A82]	[26]
Clofarabine	DMCVJ86	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Clofarabine.	Mature B-cell lymphoma [2A85]	[34]
Exjade	DMHPRWG	Major	Increased risk of nephrotoxicity by the combination of Zoledronate and Exjade.	Mineral absorption/transport disorder [5C64]	[35]
Thalidomide	DM70BU5	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Thalidomide.	Multiple myeloma [2A83]	[32]
Rofecoxib	DM3P5DA	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Rofecoxib.	Osteoarthritis [FA00-FA05]	[28]
Valdecoxib	DMAY7H4	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Zoledronate and Valdecoxib.	Osteoarthritis [FA00-FA05]	[28]
Diclofenac	DMPIHLS	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Zoledronate and Diclofenac.	Osteoarthritis [FA00-FA05]	[28]
Aspirin	DM672AH	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Zoledronate and Aspirin.	Pain [MG30-MG3Z]	[33]
Etodolac	DM6WJO9	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Etodolac.	Pain [MG30-MG3Z]	[28]
Diflunisal	DM7EN8I	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Diflunisal.	Pain [MG30-MG3Z]	[28]
Ibuprofen	DM8VCBE	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Zoledronate and Ibuprofen.	Pain [MG30-MG3Z]	[28]
Nabumetone	DMAT2XH	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Zoledronate and Nabumetone.	Pain [MG30-MG3Z]	[28]
Piroxicam	DMTK234	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Piroxicam.	Pain [MG30-MG3Z]	[28]
Choline salicylate	DM8P137	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[28]
Ketorolac	DMI4EL5	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Zoledronate and Ketorolac.	Postoperative inflammation [1A00-CA43]	[28]
Bromfenac	DMKB79O	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Zoledronate and Bromfenac.	Postoperative inflammation [1A00-CA43]	[28]
Temsirolimus	DMS104F	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Temsirolimus.	Renal cell carcinoma [2C90]	[26]
Colistimethate	DMZ9BMU	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Colistimethate.	Respiratory infection [CA07-CA4Z]	[26]
Salsalate	DM13P4C	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Zoledronate and Salsalate.	Rheumatoid arthritis [FA20]	[28]
Meloxicam	DM2AR7L	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Meloxicam.	Rheumatoid arthritis [FA20]	[28]
Sulindac	DM2QHZU	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Sulindac.	Rheumatoid arthritis [FA20]	[28]
Celecoxib	DM6LOQU	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Zoledronate and Celecoxib.	Rheumatoid arthritis [FA20]	[28]
Oxaprozin	DM9UB0P	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Zoledronate and Oxaprozin.	Rheumatoid arthritis [FA20]	[28]
Flurbiprofen	DMGN4BY	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Flurbiprofen.	Rheumatoid arthritis [FA20]	[28]
Fenoprofen	DML5VQ0	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Zoledronate and Fenoprofen.	Rheumatoid arthritis [FA20]	[28]
Tolmetin	DMWUIJE	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Tolmetin.	Rheumatoid arthritis [FA20]	[28]
Salicyclic acid	DM2F8XZ	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Zoledronate and Salicyclic acid.	Seborrhoeic dermatitis [EA81]	[33]
Bacitracin	DM5OHYE	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Bacitracin.	Skin and skin-structure infection [1F28-1G0Z]	[26]
Cisplatin	DMRHGI9	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Cisplatin.	Solid tumour/cancer [2A00-2F9Z]	[26]
Telavancin	DM58VQX	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Telavancin.	Staphylococcal/streptococcal disease [1B5Y]	[26]
Lenvatinib	DMB1IU4	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Lenvatinib.	Thyroid cancer [2D10]	[26]
Sirolimus	DMGW1ID	Major	Increased risk of nephrotoxicity by the combination of Zoledronate and Sirolimus.	Transplant rejection [NE84]	[36]
Tacrolimus	DMZ7XNQ	Major	Increased risk of nephrotoxicity by the combination of Zoledronate and Tacrolimus.	Transplant rejection [NE84]	[36]
Olsalazine	DMZW9HA	Moderate	Increased risk of nephrotoxicity by the combination of Zoledronate and Olsalazine.	Ulcerative colitis [DD71]	[26]
Plazomicin	DMKMBES	Moderate	Increased risk of hypocalcemia by the combination of Zoledronate and Plazomicin.	Urinary tract infection [GC08]	[26]

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