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

Similar Structures

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
Boniva	Injection, solution	3 mg/3mL	Intravenous	Physicians Total Care, Inc.	2007-10-16	2010-06-30
Boniva	Tablet, film coated	2.5 mg/1	Oral	Roche Pharmaceuticals	2006-07-20	2006-10-05
Boniva	Injection, solution	3 mg/3mL	Intravenous	Genentech, Inc.	2006-01-06	Not applicable
Boniva	Tablet, film coated	150 mg/1	Oral	Physicians Total Care, Inc.	2005-06-02	Not applicable
Boniva	Tablet, film coated	150 mg/1	Oral	Genentech, Inc.	2005-03-24	Not applicable
Boniva	Injection, solution	3 mg/3mL	Intravenous	UNSPECIFIED	2006-08-07	2006-08-07
Bonviva	Tablet, film coated	150 mg	Oral	Atnahs Pharma Uk Limited	2004-02-23	Not applicable
Bonviva	Injection, solution	3 mg	Intravenous	Atnahs Pharma Uk Limited	2004-02-23	Not applicable
Bonviva	Injection, solution	3 mg	Intravenous	Atnahs Pharma Uk Limited	2004-02-23	Not applicable

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Iasibon	Tablet, film coated	50 mg	Oral	Pharmathen S.A.	2011-01-21	Not applicable
Iasibon	Tablet, film coated	50 mg	Oral	Pharmathen S.A.	2011-01-21	Not applicable
Iasibon	Injection, solution, concentrate	6 mg	Intravenous	Pharmathen S.A.	2011-01-21	Not applicable
Iasibon	Injection, solution, concentrate	6 mg	Intravenous	Pharmathen S.A.	2011-01-21	Not applicable
Iasibon	Injection, solution, concentrate	6 mg	Intravenous	Pharmathen S.A.	2011-01-21	Not applicable
Iasibon	Tablet, film coated	50 mg	Oral	Pharmathen S.A.	2011-01-21	Not applicable
Iasibon	Tablet, film coated	50 mg	Oral	Pharmathen S.A.	2011-01-21	Not applicable
Iasibon	Injection, solution, concentrate	2 mg	Intravenous	Pharmathen S.A.	2011-01-21	Not applicable
Iasibon	Tablet, film coated	50 mg	Oral	Pharmathen S.A.	2011-01-21	Not applicable
Iasibon	Injection, solution, concentrate	1 mg	Intravenous	Pharmathen S.A.	2011-01-21	Not applicable

International/Other Brands

ADRONiL

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

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	inhibitor	Humans
AHydroxylapatite	antagonist	Humans

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

M05BB09 — Ibandronic acid and colecalciferol

PDB Entries

2f94 / 4umj

FDA label

Download (296 KB)

MSDS

Download (16 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Not Available	Healthy Volunteers	1
1	Completed	Treatment	Healthy Volunteers	1
2	Completed	Treatment	Cancer, Breast	1
2	Completed	Treatment	Pain; Bone Neoplasms; Neoplasm Metastasis	1
2	Completed	Treatment	Postmenopausal Osteoporosis (PMO)	1
2	Recruiting	Treatment	Osteoporosis	1
2	Unknown Status	Treatment	Cancer, Breast	1
2	Withdrawn	Treatment	Bone Neoplasms / Neoplasms Metastasis / Pain NOS	1
2, 3	Completed	Treatment	Osteoporosis	1
2, 3	Unknown Status	Treatment	Transplant, Kidney	1
3	Active Not Recruiting	Treatment	Cancer, Breast	1
3	Completed	Supportive Care	Metastatic Cancers / Pain NOS / Prostate Cancer	1
3	Completed	Treatment	Bone Marrow Edema of the Knee / Osteonecrosis of the Knee	1
3	Completed	Treatment	Cancer, Breast	1
3	Completed	Treatment	Haematological Malignancies	1
3	Completed	Treatment	Male Osteoporosis	1
3	Completed	Treatment	Osteoporosis	1
3	Completed	Treatment	Pain; Bone Neoplasms; Neoplasm Metastasis	2
3	Completed	Treatment	Post-Menopausal Osteopenia	1
3	Completed	Treatment	Postmenopausal Osteoporosis (PMO)	6
3	Completed	Treatment	Postmenopausal Women With Osteoporosis	1
3	Completed	Treatment	Primary Osteoporosis	1
3	Terminated	Treatment	Aseptic / Aseptic Hip Necrosis / Hip Necrosis	1
3	Terminated	Treatment	Bone Neoplasms / Neoplasms Metastasis / Pain NOS	2
3	Terminated	Treatment	Multiple Myeloma (MM)	1
3	Unknown Status	Treatment	Cancer, Breast / Hypercalcemia of Malignancy / Metastatic Cancers	1
3	Withdrawn	Supportive Care	Cancer, Breast / Hypercalcemia of Malignancy / Metastatic Cancers / Pain NOS	1
4	Completed	Prevention	Osteopenia / Osteoporosis / Rheumatoid Arthritis	1
4	Completed	Treatment	Osteoporosis	3
4	Completed	Treatment	Pain; Bone Neoplasms; Neoplasm Metastasis	2
4	Completed	Treatment	Post-Menopausal Osteopenia	1
4	Completed	Treatment	Postmenopausal Osteoporosis (PMO)	16
4	Completed	Treatment	Systemic Lupus Erythematosus (SLE)	1
4	No Longer Available	Not Available	Postmenopausal Osteoporosis (PMO)	1
4	Terminated	Treatment	Lung Cancers	1
4	Terminated	Treatment	Osteoporosis	1
4	Withdrawn	Treatment	Human Immunodeficiency Virus (HIV) Infections	1
Not Available	Completed	Not Available	Adenocarcinomas / Esophageal Cancers / Squamous Cell Carcinoma (SCC)	1
Not Available	Completed	Not Available	Osteoporosis	3
Not Available	Completed	Not Available	Postmenopausal Osteoporosis (PMO)	1
Not Available	Enrolling by Invitation	Not Available	Atypical Femoral Fractures / Bisphosphonate Therapy / Osteoporosis	1
Not Available	Withdrawn	Not Available	Cancer, Breast	1

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	1990-05-22	2012-03-17
CA2346662	No	2006-05-09	2019-10-01
US7192938	Yes	2007-03-20	2023-11-06
US7718634	Yes	2010-05-18	2023-11-06
US7410957	No	2008-08-12	2023-05-06
US6294196	No	2001-09-25	2019-10-07
US6143326	No	2000-11-07	2017-04-21

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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	1052	N/A	N/A	18327899
IC 50 (nM)	20	N/A	N/A	12014956
IC 50 (nM)	25.4	N/A	N/A	18327899
IC 50 (nM)	479	N/A	N/A	14613320
IC 50 (nM)	480	N/A	N/A	14613320
Ki (nM)	195	N/A	N/A	18327899
Ki (nM)	3.6	N/A	N/A	18327899
Ki (nM)	46	N/A	N/A	14613320

Details1. Farnesyl pyrophosphate synthase

Kind: Protein
Organism: Humans
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]

Details2. Hydroxylapatite

Kind

Small molecule

Organism

Humans

Pharmacological action

Yes

Actions

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 April 19, 2019 19:17

Ibandronate

Identification

Structure for Ibandronate (DB00710)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References