- Pamidronic acid
- Accession Number
- DB00282 (APRD01161)
- Small Molecule
Pamidronic acid (INN) or pamidronate disodium (USAN), marketed as pamidronate disodium pentahydrate under the brand name Aredia, is a bisphosphonate.
- Acide pamidronique
- Acido pamidronico
- Acidum pamidronicum
- Pamidronic acid
- Product Ingredients
Ingredient UNII CAS InChI Key Pamidronate Disodium C7S8VWP5DH 109552-15-0 CEYUIFJWVHOCPP-UHFFFAOYSA-L
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Aredia Injection, powder, lyophilized, for solution 90 mg/10mL Intravenous Novartis 1991-10-03 2011-09-30 Aredia Powder, for solution 60 mg Intravenous Novartis 1994-12-31 2001-07-30 Aredia Injection, powder, lyophilized, for solution 30 mg/10mL Intravenous Novartis 1991-10-31 2012-02-29 Aredia 30mg Powder, for solution 30 mg Intravenous Novartis 1994-12-31 2016-02-23 Aredia 90mg Powder, for solution 90 mg Intravenous Novartis 1994-12-31 2016-02-23 Aredia Liq Inj 3mg/ml Liquid 3 mg Intravenous Geigy Pharmaceuticals, Ciba Geigy Canada Ltd. 1992-12-31 1996-09-09 Pamidronate Disodium Injection, solution 3 mg/1mL Intravenous Bedford Pharmaceuticals 2002-03-12 2012-12-31 Pamidronate Disodium Injection, solution 9 mg/1mL Intravenous GeneraMedix, Inc. 2009-02-04 Not applicable Pamidronate Disodium Injection 9 mg/1mL Intravenous Akorn-Strides, LLC 2008-11-14 Not applicable Pamidronate Disodium Injection, solution 3 mg/1mL Intravenous GeneraMedix, Inc. 2009-02-04 Not applicable
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Pamidronate Disodium Injection, solution 3 mg/1mL Intravenous Teva Parenteral Medicines, Inc. 2002-04-01 Not applicable Pamidronate Disodium Injection, powder, lyophilized, for solution 3 mg/1mL Intravenous Areva Pharmaceuticals Inc. 2013-08-06 Not applicable Pamidronate Disodium Solution 3 mg/1mL Intravenous Barr Laboratories 2008-09-11 2012-05-22 Pamidronate Disodium Injection, powder, lyophilized, for solution 90 mg/10mL Intravenous Bedford Pharmaceuticals 2001-12-03 2012-12-31 Pamidronate Disodium Injection, solution 3 mg/1mL Intravenous Pfizer Laboratories Div Pfizer Inc. 2011-05-10 2017-12-31 Pamidronate Disodium Injection, solution 3 mg/1mL Intravenous Hospira, Inc. 2005-10-01 Not applicable Pamidronate Disodium Injection, solution 3 mg/1mL Intravenous Fresenius Kabi USA, LLC 2002-05-19 2015-08-27 Pamidronate Disodium Injection, powder, lyophilized, for solution 90 mg/10mL Intravenous Bedford Pharmaceuticals 2002-06-12 2012-08-31 Pamidronate Disodium Solution, concentrate 9 mg/1mL Intravenous Sagent Pharmaceuticals 2010-01-15 2014-12-31 Pamidronate Disodium Injection, solution 6 mg/1mL Intravenous Hospira, Inc. 2003-07-28 Not applicable
- International/Other Brands
- Aminomux / Pamimed / Ribodroat
- CAS number
- Average: 235.0695
- Chemical Formula
- InChI Key
- IUPAC Name
- (3-amino-1-hydroxy-1-phosphonopropyl)phosphonic acid
For the treatment of moderate or severe hypercalcemia associated with malignancy
- Associated Conditions
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.
Target Actions Organism AFarnesyl pyrophosphate synthaseinhibitor Humans AHydroxylapatiteantagonist Humans
Plasma concentration rises rapidly upon IV administration.
- Volume of distribution
- Not Available
- Protein binding
Approximately 54% to human serum proteins.
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
- 107 +/- 50 mlL/min
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
Pathway Category Pamidronate Action Pathway Drug action
- Pharmacogenomic Effects/ADRs
- Not Available
- Drug Interactions
Drug Interaction Abacavir Pamidronic acid may decrease the excretion rate of Abacavir which could result in a higher serum level. Acarbose Pamidronic acid may decrease the excretion rate of Acarbose which could result in a higher serum level. Aceclofenac The risk or severity of gastrointestinal bleeding can be increased when Aceclofenac is combined with Pamidronic acid. Acemetacin The risk or severity of gastrointestinal bleeding can be increased when Acemetacin is combined with Pamidronic acid. Acetaminophen Pamidronic acid may decrease the excretion rate of Acetaminophen which could result in a higher serum level. Acetylsalicylic acid The risk or severity of gastrointestinal bleeding can be increased when Acetylsalicylic acid is combined with Pamidronic acid. Acipimox The risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Pamidronic acid is combined with Acipimox. Aclidinium Pamidronic acid may decrease the excretion rate of Aclidinium which could result in a higher serum level. Acrivastine Pamidronic acid may decrease the excretion rate of Acrivastine which could result in a higher serum level. Acyclovir The risk or severity of nephrotoxicity and hypocalcemia can be increased when Acyclovir is combined with Pamidronic acid.
- Food Interactions
- Not Available
- Synthesis Reference
Edward C. Shinal, "Method for preparation of disodium pamidronate." U.S. Patent US6268524, issued February, 1988.US6268524
- General References
- 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 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)
- Download (49.3 KB)
- Clinical Trials
- 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
- 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
- Strides Arcolab Limited
- Teva Pharmaceutical Industries Ltd.
- Dosage forms
Form Route Strength Injection, powder, lyophilized, for solution Intravenous 30 mg/10mL Injection, powder, lyophilized, for solution Intravenous 90 mg/10mL Powder, for solution Intravenous 60 mg Powder, for solution Intravenous 30 mg Powder, for solution Intravenous 90 mg Liquid Intravenous 3 mg Injection Intravenous 3 mg/1mL Injection Intravenous 9 mg/1mL Injection, powder, lyophilized, for solution Intravenous 3 mg/1mL Injection, powder, lyophilized, for solution Intravenous 6 mg/1mL Injection, powder, lyophilized, for solution Intravenous 9 mg/1mL Injection, solution Intravenous 3 mg/1mL Injection, solution Intravenous 6 mg/1mL Injection, solution Intravenous 9 mg/1mL Solution Intravenous 3 mg/1mL Solution Intravenous 6 mg/1mL Solution Intravenous 9 mg/1mL Solution, concentrate Intravenous 3 mg/1mL Solution, concentrate Intravenous 9 mg/1mL Solution Intravenous 3 mg Solution Intravenous 6 mg Solution Intravenous 3.0 mg Solution Intravenous 6.0 mg Solution Intravenous 9.0 mg Powder, for solution Intravenous 15 mg Solution Intravenous 9 mg
Unit description Cost Unit Aredia 90 mg vial 839.59USD each Pamidronate disod 90 mg vial 755.64USD each Aredia 90 mg/vial 548.05USD vial Aredia 30 mg vial 279.86USD each Pamidronate Disodium 90 mg/vial 258.28USD vial Pamidronate Disodium Omega 90 mg/vial 258.28USD vial Pms-Pamidronate 90 mg/vial 258.28USD vial Aredia 30 mg/vial 182.69USD vial Pamidronate Disodium 60 mg/vial 129.14USD vial Pamidronate disod 30 mg vial 111.94USD each Pamidronate Disodium 30 mg/vial 86.09USD vial Pamidronate Disodium Omega 30 mg/vial 86.09USD vialDrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
- Not Available
- Experimental Properties
Property Value Source logP -4.7 Not Available
- Predicted Properties
Property Value Source Water Solubility 15.8 mg/mL ALOGPS logP -1.4 ALOGPS logP -4.5 ChemAxon logS -1.2 ALOGPS pKa (Strongest Acidic) 0.67 ChemAxon pKa (Strongest Basic) 9.86 ChemAxon Physiological Charge -1 ChemAxon Hydrogen Acceptor Count 8 ChemAxon Hydrogen Donor Count 6 ChemAxon Polar Surface Area 161.31 Å2 ChemAxon Rotatable Bond Count 4 ChemAxon Refractivity 42.62 m3·mol-1 ChemAxon Polarizability 17.34 Å3 ChemAxon Number of Rings 0 ChemAxon Bioavailability 1 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon
- Predicted ADMET features
Property Value Probability Human Intestinal Absorption - 0.9635 Blood Brain Barrier + 0.6175 Caco-2 permeable - 0.6924 P-glycoprotein substrate Non-substrate 0.6937 P-glycoprotein inhibitor I Non-inhibitor 0.937 P-glycoprotein inhibitor II Non-inhibitor 0.9868 Renal organic cation transporter Non-inhibitor 0.9254 CYP450 2C9 substrate Non-substrate 0.8427 CYP450 2D6 substrate Non-substrate 0.7949 CYP450 3A4 substrate Non-substrate 0.6827 CYP450 1A2 substrate Non-inhibitor 0.7892 CYP450 2C9 inhibitor Non-inhibitor 0.9049 CYP450 2D6 inhibitor Non-inhibitor 0.9336 CYP450 2C19 inhibitor Non-inhibitor 0.9049 CYP450 3A4 inhibitor Non-inhibitor 0.8539 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9924 Ames test Non AMES toxic 0.6692 Carcinogenicity Non-carcinogens 0.7877 Biodegradation Ready biodegradable 0.6385 Rat acute toxicity 1.7722 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8231 hERG inhibition (predictor II) Non-inhibitor 0.8926
- Mass Spec (NIST)
- Not Available
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
- 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.
- Organic compounds
- Super Class
- Organic acids and derivatives
- Organic phosphonic acids and derivatives
- Sub Class
- Direct Parent
- Alternative Parents
- Organic phosphonic acids / 1,3-aminoalcohols / Organopnictogen compounds / Organophosphorus compounds / Organooxygen compounds / Organic oxides / Monoalkylamines / Hydrocarbon derivatives
- 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
- Pharmacological action
- 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
- Uniprot ID
- Uniprot Name
- Farnesyl pyrophosphate synthase
- Molecular Weight
- 48275.03 Da
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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 January 21, 2019 07:05