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
Thumb
Synonyms
  • ácido ibandrónico
  • Ibandronic acid
External IDs
R484
Product Ingredients
IngredientUNIICASInChI Key
Ibandronate sodium23Y0B94E49138926-19-9LXLBEOAZMZAZND-UHFFFAOYSA-M
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BondronatLiquid1 mgIntravenousHoffmann La Roche2004-05-312006-05-17Canada
BonivaTablet, film coated150 mg/1OralGenentech, Inc.2005-03-24Not applicableUs
BonivaTablet, film coated2.5 mg/1OralRoche Pharmaceuticals2006-07-202006-10-05Us
BonivaInjection, solution3 mg/3mLIntravenousUNSPECIFIED2006-08-072006-08-07Us
BonivaInjection, solution3 mg/3mLIntravenousPhysicians Total Care, Inc.2007-10-162010-06-30Us
BonivaInjection, solution3 mg/3mLIntravenousGenentech, Inc.2006-01-06Not applicableUs
BonivaTablet, film coated150 mg/1OralPhysicians Total Care, Inc.2005-06-02Not applicableUs
BonvivaInjection, solution3 mgIntravenousAtnahs Pharma Uk Limited2004-02-23Not applicableEu
BonvivaTablet, film coated150 mgOralAtnahs Pharma Uk Limited2004-02-23Not applicableEu
BonvivaInjection, solution3 mgIntravenousAtnahs Pharma Uk Limited2004-02-23Not applicableEu
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
IasibonInjection, solution, concentrate2 mgIntravenousPharmathen S.A.2011-01-21Not applicableEu
IasibonTablet, film coated50 mgOralPharmathen S.A.2011-01-21Not applicableEu
IasibonTablet, film coated50 mgOralPharmathen S.A.2011-01-21Not applicableEu
IasibonInjection, solution, concentrate6 mgIntravenousPharmathen S.A.2011-01-21Not applicableEu
IasibonInjection, solution, concentrate1 mgIntravenousPharmathen S.A.2011-01-21Not applicableEu
IasibonTablet, film coated50 mgOralPharmathen S.A.2011-01-21Not applicableEu
IasibonInjection, solution, concentrate6 mgIntravenousPharmathen S.A.2011-01-21Not applicableEu
IasibonTablet, film coated50 mgOralPharmathen S.A.2011-01-21Not applicableEu
IasibonTablet, film coated50 mgOralPharmathen S.A.2011-01-21Not applicableEu
IasibonInjection, solution, concentrate6 mgIntravenousPharmathen S.A.2011-01-21Not applicableEu
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
BondenzaIbandronate (3 mg)Injection, solutionIntravenousRoche Registration Limited2004-02-232013-05-13Eu
BondenzaIbandronate (150 mg)Tablet, film coatedOralRoche Registration Limited2004-02-232013-05-13Eu
BondenzaIbandronate (3 mg)Injection, solutionIntravenousRoche Registration Limited2004-02-232013-05-13Eu
BondenzaIbandronate (150 mg)Tablet, film coatedOralRoche Registration Limited2004-02-232013-05-13Eu
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.

TargetActionsOrganism
AFarnesyl pyrophosphate synthase
inhibitor
Human
AHydroxylapatite
antagonist
Human
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
PathwayCategory
Ibandronate Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbexinostatThe risk or severity of QTc prolongation can be increased when Ibandronate is combined with Abexinostat.
AcebutololThe risk or severity of QTc prolongation can be increased when Ibandronate is combined with Acebutolol.
AceclofenacThe risk or severity of gastrointestinal bleeding can be increased when Aceclofenac is combined with Ibandronate.
AcemetacinThe risk or severity of gastrointestinal bleeding can be increased when Acemetacin is combined with Ibandronate.
AceprometazineThe risk or severity of QTc prolongation can be increased when Ibandronate is combined with Aceprometazine.
AcetyldigoxinThe risk or severity of QTc prolongation can be increased when Ibandronate is combined with Acetyldigoxin.
Acetylsalicylic acidThe risk or severity of gastrointestinal bleeding can be increased when Acetylsalicylic acid is combined with Ibandronate.
AcipimoxThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Ibandronate is combined with Acipimox.
AcrivastineThe risk or severity of QTc prolongation can be increased when Ibandronate is combined with Acrivastine.
AcyclovirThe 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
  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
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
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
1CompletedTreatmentHealthy Volunteers1
2CompletedTreatmentCancer, Breast1
2CompletedTreatmentPain; Bone Neoplasms; Neoplasm Metastasis1
2CompletedTreatmentPostmenopausal Osteoporosis (PMO)1
2RecruitingTreatmentOsteoporosis1
2Unknown StatusTreatmentCancer, Breast1
2WithdrawnTreatmentBone Neoplasms / Neoplasms Metastasis / Pain NOS1
2, 3CompletedTreatmentOsteoporosis1
2, 3Unknown StatusTreatmentTransplant, Kidney1
3Active Not RecruitingTreatmentCancer, Breast1
3CompletedSupportive CareMetastatic Cancers / Pain NOS / Prostate Cancer1
3CompletedTreatmentBone Marrow Edema of the Knee / Osteonecrosis of the Knee1
3CompletedTreatmentCancer, Breast1
3CompletedTreatmentHaematological Malignancies1
3CompletedTreatmentMale Osteoporosis1
3CompletedTreatmentOsteoporosis1
3CompletedTreatmentPain; Bone Neoplasms; Neoplasm Metastasis2
3CompletedTreatmentPost-Menopausal Osteopenia1
3CompletedTreatmentPostmenopausal Osteoporosis (PMO)6
3CompletedTreatmentPostmenopausal Women With Osteoporosis1
3CompletedTreatmentPrimary Osteoporosis1
3TerminatedTreatmentAseptic / Aseptic Hip Necrosis / Hip Necrosis1
3TerminatedTreatmentBone Neoplasms / Neoplasms Metastasis / Pain NOS2
3TerminatedTreatmentMultiple Myeloma (MM)1
3Unknown StatusTreatmentCancer, Breast / Hypercalcemia of Malignancy / Metastatic Cancers1
3WithdrawnSupportive CareCancer, Breast / Hypercalcemia of Malignancy / Metastatic Cancers / Pain NOS1
4CompletedPreventionOsteopenia / Osteoporosis / Rheumatoid Arthritis1
4CompletedTreatmentOsteoporosis3
4CompletedTreatmentPain; Bone Neoplasms; Neoplasm Metastasis2
4CompletedTreatmentPost-Menopausal Osteopenia1
4CompletedTreatmentPostmenopausal Osteoporosis (PMO)16
4CompletedTreatmentSystemic Lupus Erythematosus (SLE)1
4No Longer AvailableNot AvailablePostmenopausal Osteoporosis (PMO)1
4SuspendedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4TerminatedTreatmentLung Cancers1
4TerminatedTreatmentOsteoporosis1
Not AvailableCompletedNot AvailableAdenocarcinomas / Esophageal Cancers / Squamous Cell Carcinoma (SCC)1
Not AvailableCompletedNot AvailableOsteoporosis3
Not AvailableCompletedNot AvailablePostmenopausal Osteoporosis (PMO)1
Not AvailableEnrolling by InvitationNot AvailableAtypical Femoral Fractures / Bisphosphonate Therapy / Osteoporosis1
Not AvailableWithdrawnNot AvailableCancer, Breast1

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
FormRouteStrength
Injection, solutionIntravenous3 mg
Tablet, film coatedOral150 mg
LiquidIntravenous1 mg
Injection, solutionIntravenous3 mg/3mL
Tablet, film coatedOral150 mg/1
Tablet, film coatedOral2.5 mg/1
Injection, solution, concentrateIntravenous1 mg
Injection, solution, concentrateIntravenous2 mg
Injection, solution, concentrateIntravenous6 mg
Tablet, film coatedOral50 mg
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)
US4927814No1990-05-222012-03-17Us
CA2346662No2006-05-092019-10-01Canada
US7192938Yes2007-03-202023-11-06Us
US7718634Yes2010-05-182023-11-06Us
US7410957No2008-08-122023-05-06Us
US6294196No2001-09-252019-10-07Us
US6143326No2000-11-072017-04-21Us

Properties

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

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 / 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
  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]

Drug created on June 13, 2005 07:24 / Updated on November 03, 2018 15:26