Details of the Drug

General Information of Drug (ID: DMB4AVP)

Drug Name
Pamidronate
Synonyms
AHPrBP; Amidronate; Aminomux; Aminopropanehydroxydiphosphonate; Aredia; Ribodroat; Acide pamidronique; Acido pamidronico; Acidum pamidronicum; Aminohydroxypropylidene diphosphonate; Novartis brand of pamidronate disodium salt; PAMIDRONATE DISODIUM; PAMIDRONIC ACID; Pamidronate calcium; Pamidronate monosodium; Bisphosphonate 6; Acide pamidronique [INN-French]; Acido pamidronico [INN-Spanish]; Acidum pamidronicum [INN-Latin]; Pamidronic acid (INN); Pamidronic acid [INN:BAN]; Ribodroat (TN); Amino-1-hydroxypropane-1,1-diphosphonate; (3-AMINO-1-HYDROXY-1-PHOSPHONO-PROPYL)PHOSPHONIC ACID; (3-Amino-1-hydroxypropylidene)bisphosphonic acid; (3-Amino-1-hydroxypropylidene)diphosphonic acid; (3-amino-1-hydroxy-1-phosphonopropyl)phosphonic acid; (3-amino-1-hydroxypropane-1,1-diyl)bis(phosphonic acid); (3-amino-1-hydroxypropylidene)-1,1-biphosphonate; (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate; 1-hydroxy-3-aminopropane-1,1-diphosphonic acid; 3-Amino-1-hydroxypropylidene-1,1-diphosphonate
Indication
Disease Entry ICD 11 Status REF
Bone Paget disease N.A. Approved [1]
Hypercalcaemia 5B91.0 Approved [2]
Therapeutic Class
Antiinflammatory Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 2 Molecular Weight (mw) 235.07
Logarithm of the Partition Coefficient (xlogp) -6.9
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 6
Hydrogen Bond Acceptor Count (hbondacc) 8
ADMET Property
Absorption AUC
The area under the plot of plasma concentration (AUC) of drug is 10.2 +/- 6.95 mgh/L [3]
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 1.92 +/- 1.08mg/L [3]
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 4 h [3]
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [4]
Clearance
The renal clearance of drug is 49 +/- 28 mL/min [5]
Elimination
Pamidronate is exclusively eliminated in the urine, 46 +/- 16% of the dose has been eliminated in the urine [5]
Half-life
The concentration or amount of drug in body reduced by one-half in 28 +/- 7 hours [5]
Metabolism
The drug is not metabolised [5]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 5.47 micromolar/kg/day [6]
Unbound Fraction
The unbound fraction of drug in plasma is 0.7% [7]
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 1.8 L/kg [7]
Chemical Identifiers
Formula
C3H11NO7P2
IUPAC Name
(3-amino-1-hydroxy-1-phosphonopropyl)phosphonic acid
Canonical SMILES
C(CN)C(O)(P(=O)(O)O)P(=O)(O)O
InChI
InChI=1S/C3H11NO7P2/c4-2-1-3(5,12(6,7)8)13(9,10)11/h5H,1-2,4H2,(H2,6,7,8)(H2,9,10,11)
InChIKey
WRUUGTRCQOWXEG-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
4674
ChEBI ID
CHEBI:7903
CAS Number
40391-99-9
DrugBank ID
DB00282
TTD ID
D0BF8G
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
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
Geranyltranstransferase (FDPS) TTIKWV4 FPPS_HUMAN Inhibitor [8]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL) OTG7J4BP PPBT_HUMAN Gene/Protein Processing [9]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Gene/Protein Processing [10]
Bcl-2-interacting killer (BIK) OTTH1T3D BIK_HUMAN Drug Response [11]
Beta-2-microglobulin (B2M) OTDWN6NX B2MG_HUMAN Gene/Protein Processing [9]
C-reactive protein (CRP) OT0RFT8F CRP_HUMAN Gene/Protein Processing [9]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Protein Interaction/Cellular Processes [12]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Protein Interaction/Cellular Processes [12]
Collagen alpha-1(I) chain (COL1A1) OTI31178 CO1A1_HUMAN Gene/Protein Processing [13]
Fibroblast growth factor 23 (FGF23) OTZT523D FGF23_HUMAN Gene/Protein Processing [14]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Gene/Protein Processing [9]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Bone Paget disease
ICD Disease Classification
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Geranyltranstransferase (FDPS) DTT FDPS 7.06E-03 -0.73 -2.57
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Pamidronate
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
Gallium nitrate DMF9O6B Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Gallium nitrate. Mineral excesses [5B91] [15]
Coadministration of a Drug Treating the Disease Different from Pamidronate (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Remdesivir DMBFZ6L Moderate Decreased renal excretion of Pamidronate caused by Remdesivir mediated nephrotoxicity. 1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019] [16]
Framycetin DMF8DNE Moderate Increased risk of hypocalcemia by the combination of Pamidronate and Framycetin. Alcoholic liver disease [DB94] [15]
Inotersen DMJ93CT Major Increased risk of nephrotoxicity by the combination of Pamidronate and Inotersen. Amyloidosis [5D00] [16]
Kanamycin DM2DMPO Moderate Increased risk of hypocalcemia by the combination of Pamidronate and Kanamycin. Bacterial infection [1A00-1C4Z] [15]
Amikacin DM5PDRB Moderate Increased risk of hypocalcemia by the combination of Pamidronate and Amikacin. Bacterial infection [1A00-1C4Z] [15]
Streptomycin DME1LQN Moderate Increased risk of hypocalcemia by the combination of Pamidronate and Streptomycin. Bacterial infection [1A00-1C4Z] [15]
Gentamicin DMKINJO Moderate Increased risk of hypocalcemia by the combination of Pamidronate and Gentamicin. Bacterial infection [1A00-1C4Z] [15]
Capreomycin DMNZBRY Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Capreomycin. Bacterial infection [1A00-1C4Z] [15]
Netilmicin DMRD1QK Moderate Increased risk of hypocalcemia by the combination of Pamidronate and Netilmicin. Bacterial infection [1A00-1C4Z] [15]
Tobramycin DMUI0CH Moderate Increased risk of hypocalcemia by the combination of Pamidronate and Tobramycin. Bacterial infection [1A00-1C4Z] [15]
Iodipamide DMXIQYS Major Increased risk of nephrotoxicity by the combination of Pamidronate and Iodipamide. Cholelithiasis [DC11] [17]
Phenylbutazone DMAYL0T Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Phenylbutazone. Chronic pain [MG30] [18]
Ketoprofen DMRKXPT Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Ketoprofen. Chronic pain [MG30] [18]
Oxaliplatin DMQNWRD Moderate Decreased renal excretion of Pamidronate caused by Oxaliplatin mediated nephrotoxicity. Colorectal cancer [2B91] [19]
Methoxyflurane DML0RAE Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Methoxyflurane. Corneal disease [9A76-9A78] [15]
Cidofovir DMA13GD Major Increased risk of nephrotoxicity by the combination of Pamidronate and Cidofovir. Cytomegaloviral disease [1D82] [20]
Ethacrynic acid DM60QMR Moderate Increased risk of hypocalcemia by the combination of Pamidronate and Ethacrynic acid. Essential hypertension [BA00] [21]
Mefenamic acid DMK7HFI Moderate Increased risk of GI mucosal injury/bleeding risk by the combination of Pamidronate and Mefenamic acid. Female pelvic pain [GA34] [18]
Pentamidine DMHZJCG Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Pentamidine. Fungal infection [1F29-1F2F] [15]
Amphotericin B DMTAJQE Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Amphotericin B. Fungal infection [1F29-1F2F] [15]
Furosemide DMMQ8ZG Moderate Increased risk of hypocalcemia by the combination of Pamidronate and Furosemide. Heart failure [BD10-BD1Z] [21]
Bumetanide DMRV7H0 Moderate Increased risk of hypocalcemia by the combination of Pamidronate and Bumetanide. Heart failure [BD10-BD1Z] [21]
177Lu-DOTATATE DMT8GVU Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and 177Lu-DOTATATE. Hepatitis virus infection [1E50-1E51] [15]
Etelcalcetide DMHP9BL Major Increased risk of hypocalcemia by the combination of Pamidronate and Etelcalcetide. Hyper-parathyroidism [5A51] [16]
Givosiran DM5PFIJ Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Givosiran. Inborn porphyrin/heme metabolism error [5C58] [15]
Balsalazide DM7I1T9 Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Balsalazide. Indeterminate colitis [DD72] [15]
Meclofenamic acid DM05FXR Moderate Increased risk of GI mucosal injury/bleeding risk by the combination of Pamidronate and Meclofenamic acid. Inflammatory spondyloarthritis [FA92] [18]
Methotrexate DM2TEOL Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Methotrexate. Leukaemia [2A60-2B33] [15]
Moxetumomab pasudotox DMN63DZ Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Moxetumomab pasudotox. Mature B-cell leukaemia [2A82] [15]
Clofarabine DMCVJ86 Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Clofarabine. Mature B-cell lymphoma [2A85] [22]
Exjade DMHPRWG Major Increased risk of nephrotoxicity by the combination of Pamidronate and Exjade. Mineral absorption/transport disorder [5C64] [23]
Rofecoxib DM3P5DA Moderate Increased risk of GI mucosal injury/bleeding risk by the combination of Pamidronate and Rofecoxib. Osteoarthritis [FA00-FA05] [18]
Valdecoxib DMAY7H4 Moderate Increased risk of GI mucosal injury/bleeding risk by the combination of Pamidronate and Valdecoxib. Osteoarthritis [FA00-FA05] [18]
Diclofenac DMPIHLS Moderate Increased risk of GI mucosal injury/bleeding risk by the combination of Pamidronate and Diclofenac. Osteoarthritis [FA00-FA05] [18]
Naproxen DMZ5RGV Moderate Increased risk of GI mucosal injury/bleeding risk by the combination of Pamidronate and Naproxen. Osteoarthritis [FA00-FA05] [18]
Aspirin DM672AH Moderate Increased risk of GI mucosal injury/bleeding risk by the combination of Pamidronate and Aspirin. Pain [MG30-MG3Z] [18]
Diflunisal DM7EN8I Moderate Increased risk of GI mucosal injury/bleeding risk by the combination of Pamidronate and Diflunisal. Pain [MG30-MG3Z] [18]
Ibuprofen DM8VCBE Moderate Increased risk of GI mucosal injury/bleeding risk by the combination of Pamidronate and Ibuprofen. Pain [MG30-MG3Z] [18]
Nabumetone DMAT2XH Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Nabumetone. Pain [MG30-MG3Z] [18]
Piroxicam DMTK234 Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Piroxicam. Pain [MG30-MG3Z] [18]
Pemetrexed DMMX2E6 Moderate Decreased renal excretion of Pamidronate caused by Pemetrexed mediated nephrotoxicity. Pleural mesothelioma [2C26] [24]
Choline salicylate DM8P137 Moderate Increased risk of GI mucosal injury/bleeding risk by the combination of Pamidronate and Choline salicylate. Postoperative inflammation [1A00-CA43] [18]
Ketorolac DMI4EL5 Moderate Increased risk of GI mucosal injury/bleeding risk by the combination of Pamidronate and Ketorolac. Postoperative inflammation [1A00-CA43] [18]
Bromfenac DMKB79O Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Bromfenac. Postoperative inflammation [1A00-CA43] [18]
Temsirolimus DMS104F Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Temsirolimus. Renal cell carcinoma [2C90] [15]
Colistimethate DMZ9BMU Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Colistimethate. Respiratory infection [CA07-CA4Z] [15]
Salsalate DM13P4C Moderate Increased risk of GI mucosal injury/bleeding risk by the combination of Pamidronate and Salsalate. Rheumatoid arthritis [FA20] [18]
Meloxicam DM2AR7L Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Meloxicam. Rheumatoid arthritis [FA20] [18]
Sulindac DM2QHZU Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Sulindac. Rheumatoid arthritis [FA20] [18]
Celecoxib DM6LOQU Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Celecoxib. Rheumatoid arthritis [FA20] [18]
Oxaprozin DM9UB0P Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Oxaprozin. Rheumatoid arthritis [FA20] [18]
Flurbiprofen DMGN4BY Moderate Increased risk of GI mucosal injury/bleeding risk by the combination of Pamidronate and Flurbiprofen. Rheumatoid arthritis [FA20] [18]
Sulfasalazine DMICA9H Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Sulfasalazine. Rheumatoid arthritis [FA20] [15]
Fenoprofen DML5VQ0 Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Fenoprofen. Rheumatoid arthritis [FA20] [18]
Indomethacin DMSC4A7 Moderate Increased risk of GI mucosal injury/bleeding risk by the combination of Pamidronate and Indomethacin. Rheumatoid arthritis [FA20] [18]
Tolmetin DMWUIJE Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Tolmetin. Rheumatoid arthritis [FA20] [18]
Salicyclic acid DM2F8XZ Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Salicyclic acid. Seborrhoeic dermatitis [EA81] [18]
Bacitracin DM5OHYE Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Bacitracin. Skin and skin-structure infection [1F28-1G0Z] [15]
Cisplatin DMRHGI9 Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Cisplatin. Solid tumour/cancer [2A00-2F9Z] [15]
Telavancin DM58VQX Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Telavancin. Staphylococcal/streptococcal disease [1B5Y] [15]
Lenvatinib DMB1IU4 Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Lenvatinib. Thyroid cancer [2D10] [15]
Sirolimus DMGW1ID Major Increased risk of nephrotoxicity by the combination of Pamidronate and Sirolimus. Transplant rejection [NE84] [25]
Tacrolimus DMZ7XNQ Major Increased risk of nephrotoxicity by the combination of Pamidronate and Tacrolimus. Transplant rejection [NE84] [25]
Olsalazine DMZW9HA Moderate Increased risk of nephrotoxicity by the combination of Pamidronate and Olsalazine. Ulcerative colitis [DD71] [15]
Plazomicin DMKMBES Moderate Increased risk of hypocalcemia by the combination of Pamidronate and Plazomicin. Urinary tract infection [GC08] [15]
⏷ Show the Full List of 65 DDI Information of This Drug

References

1 Pamidronate FDA Label
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: 7259).
3 Berenson JR, Rosen L, Vescio R, Lau HS, Woo M, Sioufi A, Kowalski MO, Knight RD, Seaman JJ: Pharmacokinetics of pamidronate disodium in patients with cancer with normal or impaired renal function. J Clin Pharmacol. 1997 Apr;37(4):285-90. doi: 10.1002/j.1552-4604.1997.tb04304.x.
4 BDDCS applied to over 900 drugs
5 FDA Approved Drug Products: Aredia Pamidronate Intravenous Injection
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 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
8 Detection of nonsterol isoprenoids by HPLC-MS/MS. Anal Biochem. 2008 Dec 1;383(1):18-24.
9 Pamidronate increases markers of bone formation in patients with multiple myeloma in plateau phase under interferon-alpha treatment. Calcif Tissue Int. 2001 May;68(5):285-90.
10 Bisphosphonates induce apoptosis in human breast cancer cell lines. Br J Cancer. 2000 Apr;82(8):1459-68. doi: 10.1054/bjoc.1999.1131.
11 Caspase-independent induction of apoptosis in human melanoma cells by the proapoptotic Bcl-2-related protein Nbk / Bik. Oncogene. 2005 Nov 10;24(49):7369-80. doi: 10.1038/sj.onc.1208890.
12 Pamidronate induced anti-proliferative, apoptotic, and anti-migratory effects in hepatocellular carcinoma. J Hepatol. 2006 Jan;44(1):142-50. doi: 10.1016/j.jhep.2005.09.022. Epub 2005 Nov 9.
13 Expression profile and synthesis of different collagen types I, II, III, and V of human gingival fibroblasts, osteoblasts, and SaOS-2 cells after bisphosphonate treatment. Clin Oral Investig. 2010 Feb;14(1):51-8. doi: 10.1007/s00784-009-0312-2. Epub 2009 Jul 14.
14 The role of fibroblast growth factor 23 for hypophosphatemia and abnormal regulation of vitamin D metabolism in patients with McCune-Albright syndrome. J Bone Miner Metab. 2005;23(3):231-7. doi: 10.1007/s00774-004-0589-9.
15 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]
16 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
17 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]
18 Product Information. Actonel (risedronate). Procter and Gamble Pharmaceuticals, Cincinnati, OH.
19 Product Information. Eloxatin (oxaliplatin). Sanofi Winthrop Pharmaceuticals, New York, NY.
20 Product Information. Vistide (cidofovir). Gilead Sciences, Foster City, CA.
21 Product Information. Skelid (tilundronate). Sanofi Winthrop Pharmaceuticals, New York, NY.
22 Product Information. Clolar (clofarabine). sanofi-aventis, Bridgewater, NJ.
23 Product Information. Exjade (deferasirox). Novartis Pharmaceuticals, East Hanover, NJ.
24 Product Information. Alimta (pemetrexed). Lilly, Eli and Company, Indianapolis, IN.
25 Product Information. Prograf (tacrolimus). Fujisawa, Deerfield, IL.