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Identification
NamePamidronate
Accession NumberDB00282  (APRD01161)
TypeSmall Molecule
GroupsApproved
Description

Pamidronic acid (INN) or pamidronate disodium (USAN), marketed as pamidronate disodium pentahydrate under the brand name Aredia, is a bisphosphonate. [Wikipedia]

Structure
Thumb
Synonyms
Acide pamidronique
Acido pamidronico
Acidum pamidronicum
Pamidronic acid
Ribodroat
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Arediapowder for solution60 mgintravenousNovartis Pharmaceuticals Canada Inc1994-12-312001-07-30Canada
Aredia 30mgpowder for solution30 mgintravenousNovartis Pharmaceuticals Canada Inc1994-12-312016-02-23Canada
Aredia 90mgpowder for solution90 mgintravenousNovartis Pharmaceuticals Canada Inc1994-12-312016-02-23Canada
Aredia Liq Inj 3mg/mlliquid3 mgintravenousGeigy Pharmaceuticals, Ciba Geigy Canada Ltd.1992-12-311996-09-09Canada
Pamidronate Disodium for Injectionsolution3 mgintravenousHospira Healthcare Corporation2001-08-31Not applicableCanada
Pamidronate Disodium for Injectionsolution9 mgintravenousFresenius Kabi Canada Ltd2004-03-01Not applicableCanada
Pamidronate Disodium for Injectionsolution6 mgintravenousFresenius Kabi Canada Ltd2004-03-02Not applicableCanada
Pamidronate Disodium for Injectionsolution9 mgintravenousSandoz Canada Incorporated2006-07-12Not applicableCanada
Pamidronate Disodium for Injectionsolution3 mgintravenousFresenius Kabi Canada Ltd2004-03-01Not applicableCanada
Pamidronate Disodium for Injectionsolution6 mgintravenousSandoz Canada Incorporated2006-07-12Not applicableCanada
Pamidronate Disodium for Injectionpowder for solution90 mgintravenousSandoz Canada IncorporatedNot applicableNot applicableCanada
Pamidronate Disodium for Injectionsolution3 mgintravenousSandoz Canada Incorporated2006-07-12Not applicableCanada
Pamidronate Disodium for Injectionsolution9 mgintravenousHospira Healthcare Corporation2001-08-31Not applicableCanada
Pamidronate Disodium for Injectionpowder for solution30 mgintravenousSandoz Canada IncorporatedNot applicableNot applicableCanada
Pamidronate Disodium for Injectionsolution6 mgintravenousHospira Healthcare Corporation2001-08-31Not applicableCanada
Pamidronate Disodium Omega 3 mg/mlsolution3.0 mgintravenousOmega Laboratories Ltd2007-04-18Not applicableCanada
Pamidronate Disodium Omega 6 mg/mlsolution6.0 mgintravenousOmega Laboratories Ltd2006-05-24Not applicableCanada
Pamidronate Disodium Omega 9 mg/mlsolution9.0 mgintravenousOmega Laboratories Ltd2005-07-27Not applicableCanada
PMS-pamidronatepowder for solution60 mgintravenousPharmascience IncNot applicableNot applicableCanada
PMS-pamidronatepowder for solution90 mgintravenousPharmascience Inc2003-04-23Not applicableCanada
PMS-pamidronatepowder for solution30 mgintravenousPharmascience Inc2003-04-23Not applicableCanada
PMS-pamidronatepowder for solution15 mgintravenousPharmascience IncNot applicableNot applicableCanada
Val-pamidronate Disodiumsolution9 mgintravenousValeo Pharma Inc2012-11-012015-07-17Canada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Pamidronate Disodiuminjection, solution9 mg/mLintravenousAPP Pharmaceuticals, LLC2002-05-19Not applicableUs
Pamidronate Disodiuminjection9 mg/mLintravenousSagent Pharmaceuticals2010-01-15Not applicableUs
Pamidronate Disodiuminjection, solution3 mg/mLintravenousPfizer Laboratories Div Pfizer Inc2011-05-10Not applicableUs
Pamidronate Disodiuminjection3 mg/mLintravenousMylan Institutional LLC2008-11-01Not applicableUs
Pamidronate Disodiuminjection, solution3 mg/mLintravenousAPP Pharmaceuticals, LLC2002-05-19Not applicableUs
Pamidronate Disodiuminjection3 mg/mLintravenousSagent Pharmaceuticals2010-01-15Not applicableUs
Pamidronate Disodiuminjection, solution9 mg/mLintravenousHospira Worldwide, Inc.2002-06-27Not applicableUs
Pamidronate Disodiuminjection, solution9 mg/mLintravenousTeva Parenteral Medicines, Inc.2002-04-01Not applicableUs
Pamidronate Disodiuminjection, solution6 mg/mLintravenousHospira Worldwide, Inc.2002-06-27Not applicableUs
Pamidronate Disodiuminjection, solution3 mg/mLintravenousTeva Parenteral Medicines, Inc.2002-04-01Not applicableUs
Pamidronate Disodiuminjection, solution3 mg/mLintravenousHospira Worldwide, Inc.2002-06-27Not applicableUs
Pamidronate Disodiuminjection, solution9 mg/mLintravenousAmerican Regent, Inc.2010-08-09Not applicableUs
Pamidronate Disodiuminjection3 mg/mLintravenousMylan Institutional LLC2008-11-01Not applicableUs
Pamidronate Disodiuminjection, powder, lyophilized, for solution9 mg/mLintravenousAreva Pharmaceuticals Inc.2013-08-06Not applicableUs
Pamidronate Disodiuminjection, solution3 mg/mLintravenousAmerican Regent, Inc.2010-07-16Not applicableUs
Pamidronate Disodiuminjection, powder, lyophilized, for solution6 mg/mLintravenousAreva Pharmaceuticals Inc.2013-08-06Not applicableUs
Pamidronate Disodiuminjection, solution3 mg/mLintravenousPfizer Laboratories Div Pfizer Inc2011-05-10Not applicableUs
Pamidronate Disodiuminjection9 mg/mLintravenousMylan Institutional LLC2008-11-01Not applicableUs
Pamidronate Disodiuminjection, powder, lyophilized, for solution3 mg/mLintravenousAreva Pharmaceuticals Inc.2013-08-06Not applicableUs
Pamidronate Disodiuminjection, solution9 mg/mLintravenousPfizer Laboratories Div Pfizer Inc2011-05-10Not applicableUs
Pamidronate Disodiuminjection9 mg/mLintravenousMylan Institutional LLC2008-11-01Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AminomuxNot Available
PamimedNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Pamidronate Disodium
Thumb
  • InChI Key: CEYUIFJWVHOCPP-UHFFFAOYNA-L
  • Monoisotopic Mass: 278.964964021
  • Average Mass: 279.0331
DBSALT000836
Categories
UNIIOYY3447OMC
CAS number40391-99-9
WeightAverage: 235.0695
Monoisotopic: 235.001074735
Chemical FormulaC3H11NO7P2
InChI KeyInChIKey=WRUUGTRCQOWXEG-UHFFFAOYSA-N
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)
IUPAC Name
(3-amino-1-hydroxy-1-phosphonopropyl)phosphonic acid
SMILES
NCCC(O)(P(O)(O)=O)P(O)(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as bisphosphonates. These are organic compounds containing two phosphonate groups linked together through a carbon atoms.
KingdomOrganic compounds
Super ClassOrganophosphorus compounds
ClassOrganic phosphonic acids and derivatives
Sub ClassBisphosphonates
Direct ParentBisphosphonates
Alternative Parents
Substituents
  • Bisphosphonate
  • Organophosphonic acid
  • 1,3-aminoalcohol
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Amine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of moderate or severe hypercalcemia associated with malignancy
PharmacodynamicsPamidronate is in a class of drugs called bisphosphonates. Pamidronate reduces breakdown of the bones. Pamidronate is used in the treatment of Paget's disease of bone; to reduce high levels of calcium in the blood associated with malignancy (cancer); and to reduce the breakdown of bone due to metastases of breast cancer or multiple myeloma.
Mechanism of actionThe mechanism of action of pamidronate is inhibition of bone resorption. Pamidronate adsorbs to calcium phosphate (hydroxyapatite) crystals in bone and may directly block dissolution of this mineral component of bone. In vitro studies also suggest that inhibition of osteoclast activity contributes to inhibition of bone resorption. Pamidronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.
Related Articles
AbsorptionPlasma concentration rises rapidly upon IV administration.
Volume of distributionNot Available
Protein bindingApproximately 54% to human serum proteins.
Metabolism

Pamidronate is not metabolized and is exclusively eliminated by renal excretion

Route of eliminationPamidronate is not metabolized and is exclusively eliminated by renal excretion.
Half lifeThe mean ± SD elimination half-life is 28 ± 7 hours
Clearance
  • 107 +/- 50 mlL/min
ToxicitySide effects include an allergic reaction, kidney problems, seizures, low levels of calcium, magnesium, or phosphorus in the blood
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Pamidronate Action PathwayDrug actionSMP00117
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9635
Blood Brain Barrier+0.6175
Caco-2 permeable-0.6924
P-glycoprotein substrateNon-substrate0.6937
P-glycoprotein inhibitor INon-inhibitor0.937
P-glycoprotein inhibitor IINon-inhibitor0.9868
Renal organic cation transporterNon-inhibitor0.9254
CYP450 2C9 substrateNon-substrate0.8427
CYP450 2D6 substrateNon-substrate0.7949
CYP450 3A4 substrateNon-substrate0.6827
CYP450 1A2 substrateNon-inhibitor0.7892
CYP450 2C9 inhibitorNon-inhibitor0.9049
CYP450 2D6 inhibitorNon-inhibitor0.9336
CYP450 2C19 inhibitorNon-inhibitor0.9049
CYP450 3A4 inhibitorNon-inhibitor0.8539
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9924
Ames testNon AMES toxic0.6692
CarcinogenicityNon-carcinogens0.7877
BiodegradationReady biodegradable0.6385
Rat acute toxicity1.7722 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8231
hERG inhibition (predictor II)Non-inhibitor0.8926
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
  • Aesgen inc
  • Akorn strides llc
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Cipla ltd
  • Generamedix inc
  • Hospira inc
  • Mn pharmaceuticals
  • Pharmaforce inc
  • Pliva lachema as
  • Sun pharma global inc
  • Teva parenteral medicines inc
Packagers
Dosage forms
FormRouteStrength
Powder for solutionintravenous60 mg
Liquidintravenous3 mg
Injectionintravenous3 mg/mL
Injectionintravenous9 mg/mL
Injection, powder, lyophilized, for solutionintravenous3 mg/mL
Injection, powder, lyophilized, for solutionintravenous6 mg/mL
Injection, powder, lyophilized, for solutionintravenous9 mg/mL
Injection, solutionintravenous3 mg/mL
Injection, solutionintravenous6 mg/mL
Injection, solutionintravenous9 mg/mL
Solutionintravenous3 mg
Solutionintravenous6 mg
Solutionintravenous9 mg
Solutionintravenous3.0 mg
Solutionintravenous6.0 mg
Solutionintravenous9.0 mg
Powder for solutionintravenous15 mg
Powder for solutionintravenous30 mg
Powder for solutionintravenous90 mg
Prices
Unit descriptionCostUnit
Aredia 90 mg vial839.59USD each
Pamidronate disod 90 mg vial755.64USD each
Aredia 90 mg/vial548.05USD vial
Aredia 30 mg vial279.86USD each
Pamidronate Disodium 90 mg/vial258.28USD vial
Pamidronate Disodium Omega 90 mg/vial258.28USD vial
Pms-Pamidronate 90 mg/vial258.28USD vial
Aredia 30 mg/vial182.69USD vial
Pamidronate Disodium 60 mg/vial129.14USD vial
Pamidronate disod 30 mg vial111.94USD each
Pamidronate Disodium 30 mg/vial86.09USD vial
Pamidronate Disodium Omega 30 mg/vial86.09USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP-4.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility15.8 mg/mLALOGPS
logP-1.4ALOGPS
logP-4.5ChemAxon
logS-1.2ALOGPS
pKa (Strongest Acidic)0.67ChemAxon
pKa (Strongest Basic)9.86ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area161.31 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity42.62 m3·mol-1ChemAxon
Polarizability17.34 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Edward C. Shinal, “Method for preparation of disodium pamidronate.” U.S. Patent US6268524, issued February, 1988.

US6268524
General References
  1. Zarychanski R, Elphee E, Walton P, Johnston J: Osteonecrosis of the jaw associated with pamidronate therapy. Am J Hematol. 2006 Jan;81(1):73-5. [PubMed:16369966 ]
External Links
ATC CodesM05BA03
AHFS Codes
  • 92:00.00
PDB EntriesNot Available
FDA labelDownload (59.5 KB)
MSDSDownload (49.3 KB)
Interactions
Drug Interactions
Drug
AmikacinAmikacin may increase the activities of Pamidronate.
ArbekacinArbekacin may increase the activities of Pamidronate.
AxitinibThe risk or severity of adverse effects can be increased when Axitinib is combined with Pamidronate.
BevacizumabThe risk or severity of adverse effects can be increased when Bevacizumab is combined with Pamidronate.
CabozantinibThe risk or severity of adverse effects can be increased when Cabozantinib is combined with Pamidronate.
CelecoxibThe risk or severity of adverse effects can be increased when Celecoxib is combined with Pamidronate.
DeferasiroxThe risk or severity of adverse effects can be increased when Pamidronate is combined with Deferasirox.
DiclofenacThe risk or severity of adverse effects can be increased when Diclofenac is combined with Pamidronate.
DiflunisalThe risk or severity of adverse effects can be increased when Diflunisal is combined with Pamidronate.
EsomeprazoleThe therapeutic efficacy of Pamidronate can be decreased when used in combination with Esomeprazole.
EtodolacThe risk or severity of adverse effects can be increased when Etodolac is combined with Pamidronate.
FenoprofenThe risk or severity of adverse effects can be increased when Fenoprofen is combined with Pamidronate.
FloctafenineThe risk or severity of adverse effects can be increased when Floctafenine is combined with Pamidronate.
FlurbiprofenThe risk or severity of adverse effects can be increased when Flurbiprofen is combined with Pamidronate.
FramycetinFramycetin may increase the activities of Pamidronate.
GentamicinGentamicin may increase the activities of Pamidronate.
IbuprofenThe risk or severity of adverse effects can be increased when Ibuprofen is combined with Pamidronate.
IndomethacinThe risk or severity of adverse effects can be increased when Indomethacin is combined with Pamidronate.
InfliximabThe risk or severity of adverse effects can be increased when Infliximab is combined with Pamidronate.
KanamycinKanamycin may increase the activities of Pamidronate.
KetoprofenThe risk or severity of adverse effects can be increased when Ketoprofen is combined with Pamidronate.
KetorolacThe risk or severity of adverse effects can be increased when Ketorolac is combined with Pamidronate.
LansoprazoleThe therapeutic efficacy of Pamidronate can be decreased when used in combination with Lansoprazole.
LenalidomideThe risk or severity of adverse effects can be increased when Lenalidomide is combined with Pamidronate.
Mefenamic acidThe risk or severity of adverse effects can be increased when Mefenamic acid is combined with Pamidronate.
MeloxicamThe risk or severity of adverse effects can be increased when Meloxicam is combined with Pamidronate.
NabumetoneThe risk or severity of adverse effects can be increased when Nabumetone is combined with Pamidronate.
NaproxenThe risk or severity of adverse effects can be increased when Naproxen is combined with Pamidronate.
NeomycinNeomycin may increase the activities of Pamidronate.
NetilmicinNetilmicin may increase the activities of Pamidronate.
OmeprazoleThe therapeutic efficacy of Pamidronate can be decreased when used in combination with Omeprazole.
OxaprozinThe risk or severity of adverse effects can be increased when Oxaprozin is combined with Pamidronate.
PantoprazoleThe therapeutic efficacy of Pamidronate can be decreased when used in combination with Pantoprazole.
PazopanibThe risk or severity of adverse effects can be increased when Pazopanib is combined with Pamidronate.
PiroxicamThe risk or severity of adverse effects can be increased when Piroxicam is combined with Pamidronate.
PomalidomideThe risk or severity of adverse effects can be increased when Pomalidomide is combined with Pamidronate.
RabeprazoleThe therapeutic efficacy of Pamidronate can be decreased when used in combination with Rabeprazole.
RamucirumabThe risk or severity of adverse effects can be increased when Ramucirumab is combined with Pamidronate.
RegorafenibThe risk or severity of adverse effects can be increased when Regorafenib is combined with Pamidronate.
RibostamycinRibostamycin may increase the activities of Pamidronate.
SorafenibThe risk or severity of adverse effects can be increased when Sorafenib is combined with Pamidronate.
SpectinomycinSpectinomycin may increase the activities of Pamidronate.
StreptomycinStreptomycin may increase the activities of Pamidronate.
SulindacThe risk or severity of adverse effects can be increased when Sulindac is combined with Pamidronate.
SunitinibThe risk or severity of adverse effects can be increased when Sunitinib is combined with Pamidronate.
ThalidomideThalidomide may increase the nephrotoxic activities of Pamidronate.
Tiaprofenic acidThe risk or severity of adverse effects can be increased when Tiaprofenic acid is combined with Pamidronate.
TobramycinTobramycin may increase the activities of Pamidronate.
TolmetinThe risk or severity of adverse effects can be increased when Tolmetin is combined with Pamidronate.
VandetanibThe risk or severity of adverse effects can be increased when Vandetanib is combined with Pamidronate.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Poly(a) rna binding
Specific Function:
Key enzyme in isoprenoid biosynthesis which catalyzes the formation of farnesyl diphosphate (FPP), a precursor for several classes of essential metabolites including sterols, dolichols, carotenoids, and ubiquinones. FPP also serves as substrate for protein farnesylation and geranylgeranylation. Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, d...
Gene Name:
FDPS
Uniprot ID:
P14324
Molecular Weight:
48275.03 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Bergstrom JD, Bostedor RG, Masarachia PJ, Reszka AA, Rodan G: Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase. Arch Biochem Biophys. 2000 Jan 1;373(1):231-41. [PubMed:10620343 ]
  3. Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD, Ebetino FH, Rogers MJ: Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther. 2001 Feb;296(2):235-42. [PubMed:11160603 ]
  4. Notarnicola M, Messa C, Cavallini A, Bifulco M, Tecce MF, Eletto D, Di Leo A, Montemurro S, Laezza C, Caruso MG: Higher farnesyl diphosphate synthase activity in human colorectal cancer inhibition of cellular apoptosis. Oncology. 2004;67(5-6):351-8. [PubMed:15713990 ]
  5. Riebeling C, Forsea AM, Raisova M, Orfanos CE, Geilen CC: The bisphosphonate pamidronate induces apoptosis in human melanoma cells in vitro. Br J Cancer. 2002 Jul 29;87(3):366-71. [PubMed:12177810 ]
  6. Zhang PL, Lun M, Siegelmann-Danieli N, Blasick TM, Brown RE: Pamidronate resistance and associated low ras levels in breast cancer cells: a role for combinatorial therapy. Ann Clin Lab Sci. 2004 Summer;34(3):263-70. [PubMed:15487700 ]
Kind
Small molecule
Organism
Human
Pharmacological action
yes
Actions
antagonist
References
  1. Jahnke W, Henry C: An in vitro assay to measure targeted drug delivery to bone mineral. ChemMedChem. 2010 May 3;5(5):770-6. doi: 10.1002/cmdc.201000016. [PubMed:20209564 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:09