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Identification
NameRisedronate
Accession NumberDB00884  (APRD00410, DB02782)
Typesmall molecule
Groupsapproved, investigational
Description

Risedronate is a bisphosphonate used to strengthen bone, treat or prevent osteoporosis, and treat Paget’s disease of bone.

Structure
Thumb
Synonyms
SynonymLanguageCode
Acide risédroniqeFrenchOS: DCF
Acido risedronicoSpanishNot Available
Acidum risedronicumLatinNot Available
Risedronic acidNot AvailableOS: BAN
RisedronsäureGermanNot Available
Salts
Name/CAS Structure Properties
Risedronate sodium
Thumb
  • InChI Key: DRFDPXKCEWYIAW-UHFFFAOYNA-M
  • Monoisotopic Mass: 304.983019378
  • Average Mass: 305.0941
DBSALT000494
Brand names
NameCompany
ActonelSanofi-Aventis
AtelviaWarner Chilcott
BenetTakeda
Brand mixtures
Brand NameIngredients
Actonal Plus Calcium (Warner Chilcott)risedronate sodium hemi-pentahydrate + calcium carbonate
Actonel with Calcium (Procter & Gamble)risedronate sodium + calcium carbonate
Categories
CAS number105462-24-6
WeightAverage: 283.1123
Monoisotopic: 283.001074735
Chemical FormulaC7H11NO7P2
InChI KeyIIDJRNMFWXDHID-UHFFFAOYSA-N
InChI
InChI=1S/C7H11NO7P2/c9-7(16(10,11)12,17(13,14)15)4-6-2-1-3-8-5-6/h1-3,5,9H,4H2,(H2,10,11,12)(H2,13,14,15)
IUPAC Name
[1-hydroxy-1-phosphono-2-(pyridin-3-yl)ethyl]phosphonic acid
SMILES
OC(CC1=CN=CC=C1)(P(O)(O)=O)P(O)(O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassPyridines and Derivatives
SubclassNot Available
Direct parentPyridines and Derivatives
Alternative parentsOrganic Phosphonic Acids; Polyamines
Substituentsphosphonic acid; phosphonic acid derivative; polyamine; organonitrogen compound
Classification descriptionThis compound belongs to the pyridines and derivatives. These are compounds containing a pyridine ring, which is a six-member aromatic heterocycle which consists of one nitrogen atom and five carbon atoms.
Pharmacology
IndicationFor the treatment of Paget's disease of the bone (osteitis deformans), postmenopausal and glucocorticoid-induced osteoporosis
PharmacodynamicsRisedronate is a pyridinyl bisphosphonate that inhibits osteoclast-mediated bone resorption and modulates bone metabolism and is indicated for the treatment and prevention of osteoporosis in postmenopausal women.
Mechanism of actionThe action of risedronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Risedronate 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.
AbsorptionRapid absorption (~1 hr) after an oral dose, occurs throughout the upper gastrointestinal tract
Volume of distribution
  • 13.8 L/kg
Protein binding~24%
Metabolism

No evidence found for metabolization of risedronate in humans or mammals

Route of eliminationRisedronate is excreted unchanged primarily via the kidney. Insignificant amounts (<0.1% of intravenous dose) of drug are excreted in the bile in rats.
Half life1.5 hours
Clearance
  • 122 mL/min
  • 73 mL/min [osteopenic postmenopausal women]
ToxicitySide effects include abdominal pain, anxiety, back pain, belching, bladder irritation, bone disorders and pain, bronchitis, bursitis, cataracts, chest pain, colitis, constipation, depression, diarrhea, difficulty breathing, dizziness, dry eyes, eye infection, flu-like symptoms, gas, headache, high blood pressure, infection, insomnia, itching, joint disorders and pain, leg cramps, muscle pain, muscle weakness, nausea, neck pain, nerve pain, pain, pneumonia, rash, ringing in ears, sinus problems, sore throat, stomach bleeding, stuffy or runny nose, swelling, tendon problems, tumor, ulcers, urinary tract infection, vertigo, vision problems, and weakness.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Risedronate Action PathwayDrug actionSMP00112
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.9357
Blood Brain Barrier + 0.9172
Caco-2 permeable - 0.6795
P-glycoprotein substrate Non-substrate 0.6846
P-glycoprotein inhibitor I Non-inhibitor 0.9582
P-glycoprotein inhibitor II Non-inhibitor 1.0
Renal organic cation transporter Non-inhibitor 0.9542
CYP450 2C9 substrate Non-substrate 0.8452
CYP450 2D6 substrate Non-substrate 0.8162
CYP450 3A4 substrate Non-substrate 0.7208
CYP450 1A2 substrate Non-inhibitor 0.8778
CYP450 2C9 substrate Non-inhibitor 0.8792
CYP450 2D6 substrate Non-inhibitor 0.9062
CYP450 2C19 substrate Non-inhibitor 0.8777
CYP450 3A4 substrate Non-inhibitor 0.9068
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.989
Ames test Non AMES toxic 0.7663
Carcinogenicity Non-carcinogens 0.8386
Biodegradation Not ready biodegradable 0.5058
Rat acute toxicity 2.1053 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9095
hERG inhibition (predictor II) Non-inhibitor 0.9303
Pharmacoeconomics
Manufacturers
  • Warner chilcott co llc
  • Teva pharmaceuticals usa
  • Procter & Gamble
Packagers
Dosage forms
FormRouteStrength
Tablet, film coatedOral150 mg
Tablet, film coatedOral30 mg
Tablet, film coatedOral35 mg
Tablet, film coatedOral5 mg
Tablet, film coatedOral75 mg
Prices
Unit descriptionCostUnit
Actonel 150 mg tablet125.1USDtablet
Actonel 4 35 mg tablet Disp Pack119.43USDdisp
Actonel 75 mg tablet54.83USDtablet
Actonel 30 mg tablet29.32USDtablet
Actonel 35 mg tablet28.75USDtablet
Actonel 5 mg tablet4.13USDtablet
Actonel with calcium tablet3.92USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States71929382003-11-062023-11-06
United States60963421994-11-222011-11-22
Canada22945952001-08-212018-07-17
Canada23999762007-03-272021-02-01
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP-3.6Not Available
Predicted Properties
PropertyValueSource
water solubility1.04e+01 g/lALOGPS
logP-0.75ALOGPS
logP-3.3ChemAxon
logS-1.4ALOGPS
pKa (strongest acidic)0.68ChemAxon
pKa (strongest basic)4.91ChemAxon
physiological charge-2ChemAxon
hydrogen acceptor count8ChemAxon
hydrogen donor count5ChemAxon
polar surface area148.18ChemAxon
rotatable bond count4ChemAxon
refractivity57.12ChemAxon
polarizability21.91ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Srinivasa Rao V.N Divvela, Lenin Racha, Sivakumaran Meenakshisunderam, Ramesh Dandala, “Process for the preparation of risedronate sodium hemi-pentahydrate.” U.S. Patent US20070173484, issued July 26, 2007.

US20070173484
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC08233
PubChem Compound5245
PubChem Substance46507526
ChemSpider5055
BindingDB12576
Therapeutic Targets DatabaseDAP000658
PharmGKBPA451255
HETRIS
Drug Product Database2242518
RxListhttp://www.rxlist.com/cgi/generic/risedronate.htm
Drugs.comhttp://www.drugs.com/cdi/risedronate-tablets.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/act1580.shtml
WikipediaRisedronate
ATC CodesM05BA07
AHFS Codes
  • 92:00.00
PDB Entries
FDA labelshow(1.52 MB)
MSDSshow(57 KB)
Interactions
Drug Interactions
Drug
CalciumFormation of non-absorbable complexes
Calcium AcetateCalcium Salts may decrease the serum concentration of Bisphosphonate Derivatives such as risedronate. Avoid administration of oral calcium supplements within or 30 minutes after risedronate.
Calcium ChlorideCalcium salts may decrease the serum concentration of bisphosphonate derivatives. Avoid administration of oral calcium supplements within 30 minutes after alendronate/risedronate.
Iron DextranFormation of non-absorbable complexes
MagnesiumFormation of non-absorbable complexes
Food InteractionsNot Available

Targets

1. Farnesyl pyrophosphate synthase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Farnesyl pyrophosphate synthase P14324 Details

References:

  1. 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
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  3. Coxon FP, Ebetino FH, Mules EH, Seabra MC, McKenna CE, Rogers MJ: Phosphonocarboxylate inhibitors of Rab geranylgeranyl transferase disrupt the prenylation and membrane localization of Rab proteins in osteoclasts in vitro and in vivo. Bone. 2005 Sep;37(3):349-58. Pubmed
  4. 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
  5. Ortiz-Gomez A, Jimenez C, Estevez AM, Carrero-Lerida J, Ruiz-Perez LM, Gonzalez-Pacanowska D: Farnesyl diphosphate synthase is a cytosolic enzyme in Leishmania major promastigotes and its overexpression confers resistance to risedronate. Eukaryot Cell. 2006 Jul;5(7):1057-64. Pubmed
  6. Russell RG, Xia Z, Dunford JE, Oppermann U, Kwaasi A, Hulley PA, Kavanagh KL, Triffitt JT, Lundy MW, Phipps RJ, Barnett BL, Coxon FP, Rogers MJ, Watts NB, Ebetino FH: Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann N Y Acad Sci. 2007 Nov;1117:209-57. Pubmed

2. Hydroxylapatite

Kind: small molecule

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details

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. Pubmed
  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

Enzymes

1. Prostaglandin G/H synthase 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Prostaglandin G/H synthase 2 P35354 Details

References:

  1. Valenti MT, Giannini S, Donatelli L, Zanatta M, Bertoldo F, Sella S, Vilei MT, Ossi E, Realdi G, Lo Cascio V, Dalle Carbonare L: The effect of risedronate on osteogenic lineage is mediated by cyclooxygenase-2 gene upregulation. Arthritis Res Ther. 2010;12(4):R163. Epub 2010 Aug 25. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12