Identification

Name
Pamidronate
Accession Number
DB00282  (APRD01161)
Type
Small Molecule
Groups
Approved
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
Product Ingredients
IngredientUNIICASInChI Key
Pamidronate DisodiumC7S8VWP5DH109552-15-0CEYUIFJWVHOCPP-UHFFFAOYSA-L
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ArediaPowder, for solution60 mgIntravenousNovartis1994-12-312001-07-30Canada
ArediaInjection, powder, lyophilized, for solution90 mg/10mLIntravenousNovartis1991-10-032011-09-30Us
ArediaInjection, powder, lyophilized, for solution30 mg/10mLIntravenousNovartis1991-10-312012-02-29Us
Aredia 30mgPowder, for solution30 mgIntravenousNovartis1994-12-312016-02-23Canada
Aredia 90mgPowder, for solution90 mgIntravenousNovartis1994-12-312016-02-23Canada
Aredia Liq Inj 3mg/mlLiquid3 mgIntravenousGeigy Pharmaceuticals, Ciba Geigy Canada Ltd.1992-12-311996-09-09Canada
Pamidronate DisodiumInjection, solution3 mg/1mLIntravenousBedford Pharmaceuticals2002-03-282010-09-30Us
Pamidronate DisodiumInjection, solution9 mg/1mLIntravenousGeneraMedix, Inc.2009-02-04Not applicableUs
Pamidronate DisodiumInjection3 mg/1mLIntravenousAkorn-Strides, LLC2008-11-14Not applicableUs
Pamidronate DisodiumInjection, solution3 mg/1mLIntravenousGeneraMedix, Inc.2009-02-04Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Pamidronate DisodiumInjection, solution3 mg/1mLIntravenousAmerican Regent2010-07-162018-09-06Us
Pamidronate DisodiumInjection, solution9 mg/1mLIntravenousHospira, Inc.2005-10-01Not applicableUs
Pamidronate DisodiumInjection, powder, lyophilized, for solution90 mg/10mLIntravenousBedford Pharmaceuticals2001-12-032012-12-31Us
Pamidronate DisodiumInjection3 mg/1mLIntravenousMylan Institutional2011-05-102018-11-30Us
Pamidronate DisodiumInjection, powder, lyophilized, for solution90 mg/10mLIntravenousBedford Pharmaceuticals2002-06-122012-08-31Us
Pamidronate DisodiumInjection, solution3 mg/1mLIntravenousPfizer Laboratories Div Pfizer Inc.2011-05-102017-12-31Us
Pamidronate DisodiumInjection, powder, lyophilized, for solution6 mg/1mLIntravenousAreva Pharmaceuticals,Inc.2013-08-06Not applicableUs
Pamidronate DisodiumSolution6 mg/1mLIntravenousBarr Laboratories2008-09-112012-05-22Us
Pamidronate DisodiumInjection, solution3 mg/1mLIntravenousAPP Pharmaceuticals, Inc.2002-05-19Not applicableUs
Pamidronate DisodiumSolution, concentrate3 mg/1mLIntravenousSagent Pharmaceuticals2010-01-152014-12-31Us
International/Other Brands
Aminomux / Pamimed
Categories
UNII
OYY3447OMC
CAS number
40391-99-9
Weight
Average: 235.0695
Monoisotopic: 235.001074735
Chemical Formula
C3H11NO7P2
InChI Key
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

Pharmacology

Indication

For the treatment of moderate or severe hypercalcemia associated with malignancy

Associated Conditions
Pharmacodynamics

Pamidronate 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 action

The 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.

TargetActionsOrganism
AFarnesyl pyrophosphate synthase
inhibitor
Human
AHydroxylapatite
antagonist
Human
Absorption

Plasma concentration rises rapidly upon IV administration.

Volume of distribution
Not Available
Protein binding

Approximately 54% to human serum proteins.

Metabolism

Pamidronate is not metabolized and is exclusively eliminated by renal excretion

Route of elimination

Pamidronate is not metabolized and is exclusively eliminated by renal excretion.

Half life

The mean ± SD elimination half-life is 28 ± 7 hours

Clearance
  • 107 +/- 50 mlL/min
Toxicity

Side 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
PathwayCategory
Pamidronate Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbacavirPamidronate may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarbosePamidronate may decrease the excretion rate of Acarbose which could result in a higher serum level.
AceclofenacThe risk or severity of gastrointestinal bleeding can be increased when Aceclofenac is combined with Pamidronate.
AcemetacinThe risk or severity of gastrointestinal bleeding can be increased when Acemetacin is combined with Pamidronate.
AcetaminophenPamidronate may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Acetylsalicylic acidThe risk or severity of gastrointestinal bleeding can be increased when Acetylsalicylic acid is combined with Pamidronate.
AcipimoxThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Pamidronate is combined with Acipimox.
AclidiniumPamidronate may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastinePamidronate may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirThe risk or severity of nephrotoxicity and hypocalcemia can be increased when Acyclovir is combined with Pamidronate.
Food Interactions
Not 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
Human Metabolome Database
HMDB0014427
KEGG Compound
C07395
PubChem Compound
4674
PubChem Substance
46504823
ChemSpider
4512
BindingDB
12581
ChEMBL
CHEMBL834
Therapeutic Targets Database
DAP001416
PharmGKB
PA450767
HET
210
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pamidronate
ATC Codes
M05BA03 — Pamidronic acid
AHFS Codes
  • 92:24.00 — Bone Resorption Inhibitors
PDB Entries
2f89 / 3sdr / 4kpj / 4nkf / 4ogu / 5erm / 5ero
FDA label
Download (59.5 KB)
MSDS
Download (49.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentRefractory Multiple Myeloma / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentSAPHO Syndrome1
1Unknown StatusTreatmentArthroplasty / Mineral Density1
1Unknown StatusTreatmentBack Pain Lower Back1
1, 2CompletedTreatmentBack Pain Lower Back Chronic1
1, 2CompletedTreatmentMultiple Myeloma and Plasma Cell Neoplasm / Pain NOS1
1, 2TerminatedTreatmentOsteoporosis1
2CompletedTreatmentCancer, Breast1
2CompletedTreatmentMultiple Myeloma (MM)2
2CompletedTreatmentMultiple Myeloma and Plasma Cell Neoplasm1
2RecruitingPreventionOsteopenia / Osteoporosis1
2RecruitingTreatmentImmune System Disease / Musculoskeletal Disorders1
2TerminatedTreatmentBreast Cancer, Metastatic / Cancer treatment1
2Unknown StatusTreatmentBack Pain / Back Pain Lower Back / Intervertebral Disc Degeneration / Magnetic Resonance Imaging (MRI) / Modic I Discopathy1
3CompletedPreventionMultiple Myeloma (MM)1
3CompletedTreatmentMultiple Myeloma and Plasma Cell Neoplasm1
3CompletedTreatmentOsteogenesis Imperfecta1
4CompletedNot AvailableCancer, Breast / Neoplasms Metastasis1
4CompletedTreatmentBone Diseases, Metabolic1
4CompletedTreatmentBone Loss1
4CompletedTreatmentCancer, Breast1
4CompletedTreatmentOsteogenesis Imperfecta / Osteoporosis / Paget's Disease of Bone1
4CompletedTreatmentOsteopenia / Renal Osteodystrophy1
4CompletedTreatmentSpondyloarthropathies1
4Not Yet RecruitingPreventionAnkylosing Spondylitis (AS)1
4RecruitingTreatmentCancer, Breast / Metastasis / Prostate Cancer1
4WithdrawnNot AvailableMetastatic Bone Disease / Tumors, Solid1
Not AvailableCompletedPreventionCerebral Palsy (CP) / Osteogenesis Imperfecta / Osteopenia / Osteoporosis / Spina Bifida1
Not AvailableCompletedTreatmentTransplant Bone Disease1
Not AvailableTerminatedTreatmentFemoral Head Avascular Necrosis1
Not AvailableWithdrawnPreventionOssification, Heterotopic1

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
  • Akorn Inc.
  • American Regent
  • APP Pharmaceuticals
  • Barr Pharmaceuticals
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Hospira Inc.
  • Novartis AG
  • Otn Generics Inc.
  • Pharmaforce Inc.
  • Pliva Inc.
  • Sagent Pharmaceuticals
  • Sandoz
  • Strides Arcolab Limited
  • Teva Pharmaceutical Industries Ltd.
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous30 mg/10mL
Injection, powder, lyophilized, for solutionIntravenous90 mg/10mL
Powder, for solutionIntravenous60 mg
Powder, for solutionIntravenous30 mg
Powder, for solutionIntravenous90 mg
LiquidIntravenous3 mg
InjectionIntravenous3 mg/1mL
InjectionIntravenous9 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous3 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous6 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous9 mg/1mL
Injection, solutionIntravenous3 mg/1mL
Injection, solutionIntravenous6 mg/1mL
Injection, solutionIntravenous9 mg/1mL
SolutionIntravenous3 mg/1mL
SolutionIntravenous6 mg/1mL
SolutionIntravenous9 mg/1mL
Solution, concentrateIntravenous3 mg/1mL
Solution, concentrateIntravenous9 mg/1mL
SolutionIntravenous3 mg
SolutionIntravenous6 mg
SolutionIntravenous3.0 mg
SolutionIntravenous6.0 mg
SolutionIntravenous9.0 mg
Powder, for solutionIntravenous15 mg
SolutionIntravenous9 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.
Patents
Not Available

Properties

State
Solid
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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Organic phosphonic acids and derivatives
Sub Class
Bisphosphonates
Direct Parent
Bisphosphonates
Alternative Parents
Organic phosphonic acids / 1,3-aminoalcohols / Organopnictogen compounds / Organophosphorus compounds / Organooxygen compounds / Organic oxides / Monoalkylamines / Hydrocarbon derivatives
Substituents
Bisphosphonate / Organophosphonic acid / 1,3-aminoalcohol / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound / Organic oxide / Hydrocarbon derivative / Primary amine / Organophosphorus compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
Not 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...
Gene Name
FDPS
Uniprot ID
P14324
Uniprot Name
Farnesyl pyrophosphate synthase
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]

Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:40