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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyIbandronate
Identification
- Name
- Ibandronate
- Accession Number
- DB00710 (APRD00231, DB04635)
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Description
Ibandronate is a nitrogen-containing bisphosphonate in the same class as alendronate and risedronate. Ibandronate inhibits osteoclast-mediated bone resorption. All of the bisphosphonates prevent the breakdown of bone by bone cells called osteoclasts. In persons who are at high risk for osteoporosis, bisphosphonates not only result in increased amounts of bone and bone strength, they also reduce the risk of hip fractures and other bone fractures.
- Structure
Structure for Ibandronate (DB00710)
- Synonyms
- ácido ibandrónico
- Ibandronic acid
- External IDs
- R484
- Product Ingredients
Ingredient UNII CAS InChI Key Ibandronate sodium 23Y0B94E49 138926-19-9 LXLBEOAZMZAZND-UHFFFAOYSA-M - Product Images
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Bondronat Liquid 1 mg Intravenous Hoffmann La Roche 2004-05-31 2006-05-17 Canada 
Boniva Tablet, film coated 150 mg/1 Oral Genentech, Inc. 2005-03-24 Not applicable US 
Boniva Tablet, film coated 2.5 mg/1 Oral Roche Pharmaceuticals 2006-07-20 2006-10-05 US Boniva Injection, solution 3 mg/3mL Intravenous UNSPECIFIED 2006-08-07 2006-08-07 US Boniva Injection, solution 3 mg/3mL Intravenous Physicians Total Care, Inc. 2007-10-16 2010-06-30 US Boniva Injection, solution 3 mg/3mL Intravenous Genentech, Inc. 2006-01-06 Not applicable US Boniva Tablet, film coated 150 mg/1 Oral Physicians Total Care, Inc. 2005-06-02 Not applicable US Bonviva Injection, solution 3 mg Intravenous Atnahs Pharma Uk Limited 2004-02-23 Not applicable EU 
Bonviva Tablet, film coated 150 mg Oral Atnahs Pharma Uk Limited 2004-02-23 Not applicable EU Bonviva Injection, solution 3 mg Intravenous Atnahs Pharma Uk Limited 2004-02-23 Not applicable EU - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Iasibon Injection, solution, concentrate 2 mg Intravenous Pharmathen S.A. 2011-01-21 Not applicable EU Iasibon Tablet, film coated 50 mg Oral Pharmathen S.A. 2011-01-21 Not applicable EU Iasibon Tablet, film coated 50 mg Oral Pharmathen S.A. 2011-01-21 Not applicable EU Iasibon Injection, solution, concentrate 6 mg Intravenous Pharmathen S.A. 2011-01-21 Not applicable EU Iasibon Injection, solution, concentrate 1 mg Intravenous Pharmathen S.A. 2011-01-21 Not applicable EU Iasibon Tablet, film coated 50 mg Oral Pharmathen S.A. 2011-01-21 Not applicable EU Iasibon Injection, solution, concentrate 6 mg Intravenous Pharmathen S.A. 2011-01-21 Not applicable EU Iasibon Tablet, film coated 50 mg Oral Pharmathen S.A. 2011-01-21 Not applicable EU Iasibon Tablet, film coated 50 mg Oral Pharmathen S.A. 2011-01-21 Not applicable EU Iasibon Injection, solution, concentrate 6 mg Intravenous Pharmathen S.A. 2011-01-21 Not applicable EU - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Bondenza Ibandronate (3 mg) Injection, solution Intravenous Roche Registration Limited 2004-02-23 2013-05-13 EU Bondenza Ibandronate (150 mg) Tablet, film coated Oral Roche Registration Limited 2004-02-23 2013-05-13 EU Bondenza Ibandronate (3 mg) Injection, solution Intravenous Roche Registration Limited 2004-02-23 2013-05-13 EU Bondenza Ibandronate (150 mg) Tablet, film coated Oral Roche Registration Limited 2004-02-23 2013-05-13 EU - International/Other Brands
- ADRONiL / Bondronat / Bonviva
- Categories
- UNII
- UMD7G2653W
- CAS number
- 114084-78-5
- Weight
- Average: 319.2289
Monoisotopic: 319.094975119 - Chemical Formula
- C9H23NO7P2
- InChI Key
- MPBVHIBUJCELCL-UHFFFAOYSA-N
- InChI
- InChI=1S/C9H23NO7P2/c1-3-4-5-7-10(2)8-6-9(11,18(12,13)14)19(15,16)17/h11H,3-8H2,1-2H3,(H2,12,13,14)(H2,15,16,17)
- IUPAC Name
- {1-hydroxy-3-[methyl(pentyl)amino]-1-phosphonopropyl}phosphonic acid
- SMILES
- CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O
Pharmacology
- Indication
For the treatment and prevention of osteoporosis in postmenopausal women.
- Associated Conditions
- Pharmacodynamics
Ibandronate is a nitrogen-containing bisphosphonate in the same class as alendronate and risedronate. Ibandronate inhibits osteoclast-mediated bone resorption. All of the bisphosphonates prevent the breakdown of bone by bone cells called osteoclasts. In persons who are at high risk for osteoporosis, bisphosphonates not only result in increased amounts of bone and bone strength, they also reduce the risk of hip fractures and other bone fractures.
- Mechanism of action
The action of ibandronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting farnesyl pyrophosphate (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 synthase inhibitorHuman AHydroxylapatite antagonistHuman - Absorption
Poorly absorbed (mean bioavailability following a 2.5 mg oral dose is about 0.6% compared to intravenous dosing). Absorption is impaired by any kind of food or drink other than plain water.
- Volume of distribution
- 90 L
- Protein binding
90.9 to 99.5% over an ibandronate concentration range of 2 to 10 ng/mL
- Metabolism
No evidence of ibandronate being metabolized in humans.
- Route of elimination
Ibandronate is eliminated by renal excretion. Unabsorbed ibandronate is eliminated unchanged in the feces.
- Half life
10-60 hours
- Clearance
- 84 to 160 mL/min [IV administration]
- Toxicity
LD50 = 811 mg/kg (rat, oral), side effects include bronchitis, pneumonia and urinary tract infections.
- Affected organisms
- Humans and other mammals
- Pathways
Pathway Category Ibandronate Action Pathway Drug action - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction Abexinostat The risk or severity of QTc prolongation can be increased when Ibandronate is combined with Abexinostat. Acebutolol The risk or severity of QTc prolongation can be increased when Ibandronate is combined with Acebutolol. Aceclofenac The risk or severity of gastrointestinal bleeding can be increased when Aceclofenac is combined with Ibandronate. Acemetacin The risk or severity of gastrointestinal bleeding can be increased when Acemetacin is combined with Ibandronate. Aceprometazine The risk or severity of QTc prolongation can be increased when Ibandronate is combined with Aceprometazine. Acetyldigoxin The risk or severity of QTc prolongation can be increased when Ibandronate is combined with Acetyldigoxin. Acetylsalicylic acid The risk or severity of gastrointestinal bleeding can be increased when Acetylsalicylic acid is combined with Ibandronate. Acipimox The risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Ibandronate is combined with Acipimox. Acrivastine The risk or severity of QTc prolongation can be increased when Ibandronate is combined with Acrivastine. Acyclovir The risk or severity of nephrotoxicity and hypocalcemia can be increased when Acyclovir is combined with Ibandronate. - Food Interactions
- Take on an empty stomach. All foods markedly reduce (up to 90%) ibandronate bioavailabilty. Take with plain water (not mineralized) at least 1 hour before any food. Bioavailability and effect on bone density are both impaired if the patient eats or drinks in less than 1 hour after taking this product. Drink a large glass of water and stay in an upright position for at least 60 minutes after taking this product.
References
- Synthesis Reference
Revital Lifshitz-Liron, Thomas Bayer, Judith Aronhime, Michael Pinchasov, "Solid and crystalline ibandronate sodium and processes for preparation thereof." U.S. Patent US20070179119, issued August 02, 2007.
US20070179119- General References
- Epstein S, Zaidi M: Biological properties and mechanism of action of ibandronate: application to the treatment of osteoporosis. Bone. 2005 Oct;37(4):433-40. [PubMed:16046205]
- External Links
- Human Metabolome Database
- HMDB0014848
- PubChem Compound
- 60852
- PubChem Substance
- 46508134
- ChemSpider
- 54839
- BindingDB
- 12577
- ChEMBL
- CHEMBL997
- Therapeutic Targets Database
- DAP001022
- PharmGKB
- PA10270
- HET
- BFQ
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Ibandronate
- ATC Codes
- M05BA06 — Ibandronic acid
- PDB Entries
- 2f94 / 4umj
- FDA label
- Download (296 KB)
- MSDS
- Download (16 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Hoffmann la roche inc
- Packagers
- Diversified Healthcare Services Inc.
- F Hoffmann La Roche Ltd.
- F Hoffmann-La Roche Ltd.
- Physicians Total Care Inc.
- Vetter Pharma Fertigung GmbH and Co. KG
- Dosage forms
Form Route Strength Injection, solution Intravenous 3 mg Tablet, film coated Oral 150 mg Liquid Intravenous 1 mg Injection, solution Intravenous 3 mg/3mL Tablet, film coated Oral 150 mg/1 Tablet, film coated Oral 2.5 mg/1 Injection, solution, concentrate Intravenous 1 mg Injection, solution, concentrate Intravenous 2 mg Injection, solution, concentrate Intravenous 6 mg Tablet, film coated Oral 50 mg Injection Intravenous 3 mg/3mL Tablet Oral 150 mg/1 - Prices
Unit description Cost Unit Boniva 3 mg/3ml Kit Box 524.22USD box Boniva 3 mg/3 ml syringe 504.06USD syringe Boniva 3 150 mg tablet Disp Pack 388.93USD disp Boniva 150 mg tablet 124.66USD tablet Boniva 2.5 mg tablet 4.16USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) US4927814 No 1995-03-17 2012-03-17 US CA2346662 No 2006-05-09 2019-10-01 Canada US7192938 Yes 2003-11-06 2023-11-06 US US7718634 Yes 2003-11-06 2023-11-06 US US7410957 No 2003-05-06 2023-05-06 US US6294196 No 1999-10-07 2019-10-07 US US6143326 No 1997-04-21 2017-04-21 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Freely soluble Not Available logP -2.1 Not Available - Predicted Properties
Property Value Source Water Solubility 13.4 mg/mL ALOGPS logP 0.26 ALOGPS logP -2.5 ChemAxon logS -1.4 ALOGPS pKa (Strongest Acidic) 0.66 ChemAxon pKa (Strongest Basic) 9.93 ChemAxon Physiological Charge -1 ChemAxon Hydrogen Acceptor Count 8 ChemAxon Hydrogen Donor Count 5 ChemAxon Polar Surface Area 138.53 Å2 ChemAxon Rotatable Bond Count 9 ChemAxon Refractivity 71.16 m3·mol-1 ChemAxon Polarizability 29.51 Å3 ChemAxon Number of Rings 0 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption - 0.9664 Blood Brain Barrier - 0.5229 Caco-2 permeable - 0.6012 P-glycoprotein substrate Substrate 0.6888 P-glycoprotein inhibitor I Non-inhibitor 0.8195 P-glycoprotein inhibitor II Non-inhibitor 0.9838 Renal organic cation transporter Non-inhibitor 0.9092 CYP450 2C9 substrate Non-substrate 0.8376 CYP450 2D6 substrate Non-substrate 0.7863 CYP450 3A4 substrate Non-substrate 0.5504 CYP450 1A2 substrate Non-inhibitor 0.832 CYP450 2C9 inhibitor Non-inhibitor 0.8159 CYP450 2D6 inhibitor Non-inhibitor 0.8987 CYP450 2C19 inhibitor Non-inhibitor 0.8045 CYP450 3A4 inhibitor Non-inhibitor 0.8901 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9945 Ames test Non AMES toxic 0.6527 Carcinogenicity Non-carcinogens 0.683 Biodegradation Not ready biodegradable 0.8346 Rat acute toxicity 2.4278 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.6061 hERG inhibition (predictor II) Non-inhibitor 0.6622
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
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
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 / Trialkylamines / Organopnictogen compounds / Organophosphorus compounds / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives
- Substituents
- Bisphosphonate / Organophosphonic acid / 1,3-aminoalcohol / Tertiary aliphatic amine / Tertiary amine / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound / Organic oxide / Hydrocarbon derivative
- 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
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- Chapurlat RD, Delmas PD: Drug insight: Bisphosphonates for postmenopausal osteoporosis. Nat Clin Pract Endocrinol Metab. 2006 Apr;2(4):211-9; quiz following 238. [PubMed:16932286]
- 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]
- Rondeau JM, Bitsch F, Bourgier E, Geiser M, Hemmig R, Kroemer M, Lehmann S, Ramage P, Rieffel S, Strauss A, Green JR, Jahnke W: Structural basis for the exceptional in vivo efficacy of bisphosphonate drugs. ChemMedChem. 2006 Feb;1(2):267-73. [PubMed:16892359]
Yes
Antagonist
References
- 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]
- Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, Mangood A, Russell RG, Ebetino FH: Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone. 2006 May;38(5):617-27. Epub 2005 Jul 20. [PubMed:16046206]
Drug created on June 13, 2005 07:24 / Updated on November 03, 2018 15:26