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Identification
NameIbandronate
Accession NumberDB00710  (APRD00231, DB04635)
TypeSmall Molecule
GroupsApproved, 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
Thumb
Synonyms
Bondronat
Ibandronic Acid
External Identifiers
  • R484
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Bondronatliquid1 mgintravenousHoffmann La Roche Limited2004-05-312006-05-17Canada
Bonivatablet, film coated150 mg/1oralGenentech, Inc.2002-07-15Not applicableUs
Bonivatablet, film coated150 mg/1oralPhysicians Total Care, Inc.2005-06-02Not applicableUs
Bonivainjection, solution3 mg/3mLintravenousGenentech, Inc.2011-06-01Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ibandronate Sodiuminjection, solution3 mg/3mLintravenousSun Pharmaceutical Industries Limited2014-02-15Not applicableUs
Ibandronate Sodiumtablet150 mg/1oralWatson Laboratories, Inc.2012-03-20Not applicableUs
Ibandronate Sodiumtablet, film coated150 mg/1oralApotex Corp2012-03-19Not applicableUs
Ibandronate Sodiuminjection, solution3 mg/3mLintravenousAuro Medics Pharma Llc2015-08-19Not applicableUs
Ibandronate Sodiumtablet150 mg/1oralDr. Reddy's Laboratories Limited2012-06-21Not applicableUs
Ibandronate Sodiumtablet150 mg/1oralAlvogen Inc.2014-05-01Not applicableUs
Ibandronate Sodiumtablet, film coated150 mg/1oralAurobindo Pharma Limited2016-03-11Not applicableUs
Ibandronate Sodiumtablet150 mg/1oralAv Kare, Inc.2013-12-04Not applicableUs
Ibandronate Sodiuminjection3 mg/3mLintravenousApotex Corp.2016-01-13Not applicableUs
Ibandronate Sodiuminjection, solution3 mg/3mLintravenousSagent Pharmaceuticals2014-09-02Not applicableUs
Ibandronate Sodiuminjection, solution3 mg/3mLintravenousMylan Institutional LLC2014-09-02Not applicableUs
Ibandronate Sodiuminjection, solution3 mg/3mLintravenousHeritage Pharmaceuticals Inc.2014-09-04Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
ADRONiLNot Available
BonvivaNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Ibandronate sodium
Thumb
  • InChI Key: LXLBEOAZMZAZND-UHFFFAOYNA-M
  • Monoisotopic Mass: 341.076919762
  • Average Mass: 341.2108
DBSALT000246
Categories
UNIIUMD7G2653W
CAS number114084-78-5
WeightAverage: 319.2289
Monoisotopic: 319.094975119
Chemical FormulaC9H23NO7P2
InChI KeyInChIKey=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
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
  • Tertiary aliphatic amine
  • Tertiary amine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment and prevention of osteoporosis in postmenopausal women.
PharmacodynamicsIbandronate 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 actionThe 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.
Related Articles
AbsorptionPoorly 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 binding90.9 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 eliminationIbandronate is eliminated by renal excretion. Unabsorbed ibandronate is eliminated unchanged in the feces.
Half life10-60 hours
Clearance
  • 84 to 160 mL/min [IV administration]
ToxicityLD50 = 811 mg/kg (rat, oral), side effects include bronchitis, pneumonia and urinary tract infections.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Ibandronate Action PathwayDrug actionSMP00079
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9664
Blood Brain Barrier-0.5229
Caco-2 permeable-0.6012
P-glycoprotein substrateSubstrate0.6888
P-glycoprotein inhibitor INon-inhibitor0.8195
P-glycoprotein inhibitor IINon-inhibitor0.9838
Renal organic cation transporterNon-inhibitor0.9092
CYP450 2C9 substrateNon-substrate0.8376
CYP450 2D6 substrateNon-substrate0.7863
CYP450 3A4 substrateNon-substrate0.5504
CYP450 1A2 substrateNon-inhibitor0.832
CYP450 2C9 inhibitorNon-inhibitor0.8159
CYP450 2D6 inhibitorNon-inhibitor0.8987
CYP450 2C19 inhibitorNon-inhibitor0.8045
CYP450 3A4 inhibitorNon-inhibitor0.8901
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9945
Ames testNon AMES toxic0.6527
CarcinogenicityNon-carcinogens0.683
BiodegradationNot ready biodegradable0.8346
Rat acute toxicity2.4278 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6061
hERG inhibition (predictor II)Non-inhibitor0.6622
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Hoffmann la roche inc
Packagers
Dosage forms
FormRouteStrength
Liquidintravenous1 mg
Injection, solutionintravenous3 mg/3mL
Tablet, film coatedoral150 mg/1
Injectionintravenous3 mg/3mL
Tabletoral150 mg/1
Prices
Unit descriptionCostUnit
Boniva 3 mg/3ml Kit Box524.22USD box
Boniva 3 mg/3 ml syringe504.06USD syringe
Boniva 3 150 mg tablet Disp Pack388.93USD disp
Boniva 150 mg tablet124.66USD tablet
Boniva 2.5 mg tablet4.16USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2346662 No2006-05-092019-10-01Canada
US4927814 No1995-03-172012-03-17Us
US6143326 No1997-04-212017-04-21Us
US6294196 No1999-10-072019-10-07Us
US7192938 No2003-05-062023-05-06Us
US7410957 No2003-05-062023-05-06Us
US7718634 No2003-05-062023-05-06Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityFreely solubleNot Available
logP-2.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility13.4 mg/mLALOGPS
logP0.26ALOGPS
logP-2.5ChemAxon
logS-1.4ALOGPS
pKa (Strongest Acidic)0.66ChemAxon
pKa (Strongest Basic)9.93ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area138.53 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity71.16 m3·mol-1ChemAxon
Polarizability29.51 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

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
  1. 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
ATC CodesM05BA06
AHFS Codes
  • 92:00
PDB Entries
FDA labelDownload (296 KB)
MSDSDownload (16 KB)
Interactions
Drug Interactions
Drug
Aluminum hydroxideThe serum concentration of Ibandronate can be decreased when it is combined with Aluminum hydroxide.
AmikacinAmikacin may increase the activities of Ibandronate.
ArbekacinArbekacin may increase the activities of Ibandronate.
BevacizumabThe risk or severity of adverse effects can be increased when Bevacizumab is combined with Ibandronate.
Calcium carbonateThe serum concentration of Ibandronate can be decreased when it is combined with Calcium carbonate.
CitalopramIbandronate may increase the QTc-prolonging activities of Citalopram.
DeferasiroxThe risk or severity of adverse effects can be increased when Ibandronate is combined with Deferasirox.
DofetilideIbandronate may increase the QTc-prolonging activities of Dofetilide.
EsomeprazoleThe therapeutic efficacy of Ibandronate can be decreased when used in combination with Esomeprazole.
FramycetinFramycetin may increase the activities of Ibandronate.
GentamicinGentamicin may increase the activities of Ibandronate.
GoserelinIbandronate may increase the QTc-prolonging activities of Goserelin.
InfliximabThe risk or severity of adverse effects can be increased when Infliximab is combined with Ibandronate.
Iron DextranThe serum concentration of Ibandronate can be decreased when it is combined with Iron Dextran.
KanamycinKanamycin may increase the activities of Ibandronate.
LansoprazoleThe therapeutic efficacy of Ibandronate can be decreased when used in combination with Lansoprazole.
LeuprolideIbandronate may increase the QTc-prolonging activities of Leuprolide.
Magnesium oxideThe serum concentration of Ibandronate can be decreased when it is combined with Magnesium oxide.
Magnesium SulfateThe serum concentration of Ibandronate can be decreased when it is combined with Magnesium Sulfate.
MifepristoneMifepristone may increase the QTc-prolonging activities of Ibandronate.
NeomycinNeomycin may increase the activities of Ibandronate.
NetilmicinNetilmicin may increase the activities of Ibandronate.
OmeprazoleThe therapeutic efficacy of Ibandronate can be decreased when used in combination with Omeprazole.
PantoprazoleThe therapeutic efficacy of Ibandronate can be decreased when used in combination with Pantoprazole.
RibostamycinRibostamycin may increase the activities of Ibandronate.
SpectinomycinSpectinomycin may increase the activities of Ibandronate.
StreptomycinStreptomycin may increase the activities of Ibandronate.
TobramycinTobramycin may increase the activities of 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.

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. 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 ]
  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. 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 ]
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 ]
  2. 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 ]
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Drug created on June 13, 2005 07:24 / Updated on May 30, 2016 02:07