Identification

Name
Clodronic Acid
Accession Number
DB00720  (APRD00639)
Type
Small Molecule
Groups
Approved, Investigational, Vet approved
Description

A diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification.

Structure
Thumb
Synonyms
  • (Dichloro-phosphono-methyl)-phosphonic acid
  • (Dichloromethylene)bisphosphonic acid
  • (Dichloromethylene)diphosphonic acid
  • Acide Clodronique
  • Acido Clodronico
  • Acidum Clodronicum
  • Clodronate
  • Clodronsaeure
  • Clodronsäure
  • Dichloromethanediphosphonic acid
  • Dichloromethylene-1,1-bisphosphonic acid
  • Dichloromethylene-1,1-diphosphonic acid
  • Dichloromethylidene diphosphonate
External IDs
BM 06.011
Product Ingredients
IngredientUNIICASInChI Key
Clodronate disodiumN030400H8J88416-50-6XWHPUCFOTRBMGS-UHFFFAOYSA-L
Clodronate disodium tetrahydrateNot AvailableNot AvailableNot applicable
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BonefosSolution60 mgIntravenousBayer1992-12-31Not applicableCanada
BonefosCapsule400 mgOralBayer1992-12-31Not applicableCanada
ClasteonCapsule400 mgOralSunovion2004-05-13Not applicableCanada
Ostac Cap 400mgCapsule400 mgOralHoffmann La Roche1994-12-312006-10-11Canada
International/Other Brands
Lodronat (Boehringer Ingelheim) / Loron (Roche) / Lytos (Roche) / Ostac (Roche) / Sindronat (Sindan)
Categories
UNII
0813BZ6866
CAS number
10596-23-3
Weight
Average: 244.892
Monoisotopic: 243.886016298
Chemical Formula
CH4Cl2O6P2
InChI Key
ACSIXWWBWUQEHA-UHFFFAOYSA-N
InChI
InChI=1S/CH4Cl2O6P2/c2-1(3,10(4,5)6)11(7,8)9/h(H2,4,5,6)(H2,7,8,9)
IUPAC Name
[dichloro(phosphono)methyl]phosphonic acid
SMILES
OP(O)(=O)C(Cl)(Cl)P(O)(O)=O

Pharmacology

Indication

For the management of hypercalcemia of malignancy and as an adjunct in the management of osteolysis resulting from bone metastases of malignant tumors.

Associated Conditions
Pharmacodynamics

Clodronate is a first generation (non-nitrogenous) bisphosphonate in the same family as etidronate and tiludronate. Clodronate affects calcium metabolism and inhibits bone resorption and soft tissue calcification. Of the clodronate that is resorbed (from oral preparation) or infused (for intravenous drugs), about 50% is excreted unchanged by the kidney. The remainder has a very high affinity for bone tissue, and is rapidly absorbed onto the bone surface. Clodronate has been shown to prevent or delay skeletal-related events and decrease bone pain as well as normalize calcium levels in the presence of hypercalcemia.

Mechanism of action

The bisphosphonate group binds strongly to the bone mineral, hydroxyapatite. This explains the specific pharmacological action of these compounds on mineralized tissues, especially bone. The exact mechanism of action of clodronate is not known, however it is known that it does not inhibit protein isoprenylation but can be metabolized intracellularly to a β-γ-methylene (AppCp-type) analog of ATP (AppCCl2p), which is cytotoxic to macrophages in vitro. Inhibition of the ADP/ATP translocase by the metabolite AppCCl2p is a likely route by which clodronate causes osteoclast apoptosis and inhibits bone resorption. Recently, the slime mold Dictyostelium discoideum was shown to take up bisphosphonates by pinocytosis. In these cells, clodronate, but not other pharmacologically active bisphosphonates, was incorporated into adenine nucleotides, which could potentially explain why this bisphosphonate sometimes seems to act differently than the other bisphosphonates. Clodronate, like all biphosphonates, also binds protein-tyrosine-phosphatase.

TargetActionsOrganism
AADP/ATP translocase 1
inhibitor
Human
AADP/ATP translocase 2
inhibitor
Human
AADP/ATP translocase 3
inhibitor
Human
AHydroxylapatite
antagonist
Human
Absorption

After oral administration, absorption is estimated at 1–3% of the ingested dose because of the low uptake from the gastrointestinal tract.

Volume of distribution
Not Available
Protein binding

2%-36%

Metabolism

Clodronate is not metabolized in humans.

Route of elimination
Not Available
Half life

Approximately 13 hours.

Clearance
Not Available
Toxicity

Decreases in serum calcium following substantial overdosage may be expected in some patients. Signs and symptoms of hypocalcemia also may occur in some of these patients.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
16-BromoepiandrosteroneThe risk or severity of adverse effects can be increased when 16-Bromoepiandrosterone is combined with Clodronic Acid.Investigational
19-norandrostenedioneThe risk or severity of adverse effects can be increased when 19-norandrostenedione is combined with Clodronic Acid.Experimental, Illicit
5-androstenedioneThe risk or severity of adverse effects can be increased when 5-androstenedione is combined with Clodronic Acid.Experimental, Illicit
AcenocoumarolClodronic Acid may increase the anticoagulant activities of Acenocoumarol.Approved, Investigational
AlaproclateAlaproclate may increase the antiplatelet activities of Clodronic Acid.Experimental
AlclometasoneThe risk or severity of adverse effects can be increased when Alclometasone is combined with Clodronic Acid.Approved
AldosteroneThe risk or severity of adverse effects can be increased when Aldosterone is combined with Clodronic Acid.Experimental, Investigational
AlmasilateThe serum concentration of Clodronic Acid can be decreased when it is combined with Almasilate.Approved, Experimental
AloglutamolThe serum concentration of Clodronic Acid can be decreased when it is combined with Aloglutamol.Approved
AluminiumThe serum concentration of Clodronic Acid can be decreased when it is combined with Aluminium.Approved, Investigational
Aluminium acetoacetateThe serum concentration of Clodronic Acid can be decreased when it is combined with Aluminium acetoacetate.Experimental
Aluminium glycinateThe serum concentration of Clodronic Acid can be decreased when it is combined with Aluminium glycinate.Experimental
Aluminum hydroxideThe serum concentration of Clodronic Acid can be decreased when it is combined with Aluminum hydroxide.Approved, Investigational
AmcinonideThe risk or severity of adverse effects can be increased when Amcinonide is combined with Clodronic Acid.Approved
AmikacinAmikacin may increase the hypocalcemic activities of Clodronic Acid.Approved, Investigational, Vet Approved
AndrostenedioneThe risk or severity of adverse effects can be increased when Androstenedione is combined with Clodronic Acid.Experimental, Illicit
AnecortaveThe risk or severity of adverse effects can be increased when Anecortave is combined with Clodronic Acid.Investigational
anecortave acetateThe risk or severity of adverse effects can be increased when anecortave acetate is combined with Clodronic Acid.Investigational
ApramycinApramycin may increase the hypocalcemic activities of Clodronic Acid.Experimental, Vet Approved
ArbekacinArbekacin may increase the hypocalcemic activities of Clodronic Acid.Approved, Investigational
AtamestaneThe risk or severity of adverse effects can be increased when Atamestane is combined with Clodronic Acid.Investigational
BazedoxifeneClodronic Acid may increase the thrombogenic activities of Bazedoxifene.Approved, Investigational
Beclomethasone dipropionateThe risk or severity of adverse effects can be increased when Beclomethasone dipropionate is combined with Clodronic Acid.Approved, Investigational
BekanamycinBekanamycin may increase the hypocalcemic activities of Clodronic Acid.Experimental
BetamethasoneThe risk or severity of adverse effects can be increased when Betamethasone is combined with Clodronic Acid.Approved, Vet Approved
Bismuth SubcitrateThe serum concentration of Clodronic Acid can be decreased when it is combined with Bismuth Subcitrate.Approved, Investigational
Bismuth subnitrateThe serum concentration of Clodronic Acid can be decreased when it is combined with Bismuth subnitrate.Approved
BudesonideThe risk or severity of adverse effects can be increased when Budesonide is combined with Clodronic Acid.Approved
Calcium AcetateThe serum concentration of Clodronic Acid can be decreased when it is combined with Calcium Acetate.Approved, Investigational
Calcium CarbonateThe serum concentration of Clodronic Acid can be decreased when it is combined with Calcium Carbonate.Approved, Investigational
Calcium ChlorideThe serum concentration of Clodronic Acid can be decreased when it is combined with Calcium Chloride.Approved
Calcium CitrateThe serum concentration of Clodronic Acid can be decreased when it is combined with Calcium Citrate.Approved
Calcium glubionateThe serum concentration of Clodronic Acid can be decreased when it is combined with Calcium glubionate.Approved
Calcium GluceptateThe serum concentration of Clodronic Acid can be decreased when it is combined with Calcium Gluceptate.Approved
Calcium gluconateThe serum concentration of Clodronic Acid can be decreased when it is combined with Calcium gluconate.Approved, Vet Approved
Calcium lactateThe serum concentration of Clodronic Acid can be decreased when it is combined with Calcium lactate.Approved, Investigational, Vet Approved
Calcium lactate gluconateThe serum concentration of Clodronic Acid can be decreased when it is combined with Calcium lactate gluconate.Experimental
Calcium levulinateThe serum concentration of Clodronic Acid can be decreased when it is combined with Calcium levulinate.Approved, Experimental
Calcium pangamateThe serum concentration of Clodronic Acid can be decreased when it is combined with Calcium pangamate.Experimental
Calcium PhosphateThe serum concentration of Clodronic Acid can be decreased when it is combined with Calcium Phosphate.Approved
Calcium silicateThe serum concentration of Clodronic Acid can be decreased when it is combined with Calcium silicate.Experimental
CaseinThe serum concentration of Clodronic Acid can be decreased when it is combined with Casein.Approved
ChlorotrianiseneClodronic Acid may increase the thrombogenic activities of Chlorotrianisene.Investigational, Withdrawn
CiclesonideThe risk or severity of adverse effects can be increased when Ciclesonide is combined with Clodronic Acid.Approved, Investigational
CitalopramCitalopram may increase the antiplatelet activities of Clodronic Acid.Approved
ClobetasolThe risk or severity of adverse effects can be increased when Clobetasol is combined with Clodronic Acid.Approved, Investigational
Clobetasol propionateThe risk or severity of adverse effects can be increased when Clobetasol propionate is combined with Clodronic Acid.Approved
ClobetasoneThe risk or severity of adverse effects can be increased when Clobetasone is combined with Clodronic Acid.Approved
ClocortoloneThe risk or severity of adverse effects can be increased when Clocortolone is combined with Clodronic Acid.Approved
ClorindioneClodronic Acid may increase the anticoagulant activities of Clorindione.Experimental
Conjugated estrogensClodronic Acid may increase the thrombogenic activities of Conjugated estrogens.Approved
Cortexolone 17α-propionateThe risk or severity of adverse effects can be increased when Cortexolone 17α-propionate is combined with Clodronic Acid.Investigational
CorticosteroneThe risk or severity of adverse effects can be increased when Corticosterone is combined with Clodronic Acid.Experimental
Cortisone acetateThe risk or severity of adverse effects can be increased when Cortisone acetate is combined with Clodronic Acid.Approved, Investigational
DaidzeinClodronic Acid may increase the thrombogenic activities of Daidzein.Experimental
DapoxetineDapoxetine may increase the antiplatelet activities of Clodronic Acid.Investigational
DeferasiroxThe risk or severity of adverse effects can be increased when Clodronic Acid is combined with Deferasirox.Approved, Investigational
DeflazacortThe risk or severity of adverse effects can be increased when Deflazacort is combined with Clodronic Acid.Approved, Investigational
DesonideThe risk or severity of adverse effects can be increased when Desonide is combined with Clodronic Acid.Approved, Investigational
DesoximetasoneThe risk or severity of adverse effects can be increased when Desoximetasone is combined with Clodronic Acid.Approved
Desoxycorticosterone acetateThe risk or severity of adverse effects can be increased when Desoxycorticosterone acetate is combined with Clodronic Acid.Approved
Desoxycorticosterone PivalateThe risk or severity of adverse effects can be increased when Desoxycorticosterone Pivalate is combined with Clodronic Acid.Experimental, Vet Approved
DesvenlafaxineDesvenlafaxine may increase the antiplatelet activities of Clodronic Acid.Approved, Investigational
DexamethasoneThe risk or severity of adverse effects can be increased when Dexamethasone is combined with Clodronic Acid.Approved, Investigational, Vet Approved
Dexamethasone isonicotinateThe risk or severity of adverse effects can be increased when Dexamethasone isonicotinate is combined with Clodronic Acid.Vet Approved
DexlansoprazoleThe therapeutic efficacy of Clodronic Acid can be decreased when used in combination with Dexlansoprazole.Approved, Investigational
DexrabeprazoleThe therapeutic efficacy of Clodronic Acid can be decreased when used in combination with Dexrabeprazole.Experimental
DibekacinDibekacin may increase the hypocalcemic activities of Clodronic Acid.Experimental
DicoumarolClodronic Acid may increase the anticoagulant activities of Dicoumarol.Approved
DienestrolClodronic Acid may increase the thrombogenic activities of Dienestrol.Approved, Investigational
DiethylstilbestrolClodronic Acid may increase the thrombogenic activities of Diethylstilbestrol.Approved, Investigational
DiflorasoneThe risk or severity of adverse effects can be increased when Diflorasone is combined with Clodronic Acid.Approved
DifluocortoloneThe risk or severity of adverse effects can be increased when Difluocortolone is combined with Clodronic Acid.Approved, Investigational, Withdrawn
DifluprednateThe risk or severity of adverse effects can be increased when Difluprednate is combined with Clodronic Acid.Approved
DihydrostreptomycinDihydrostreptomycin may increase the hypocalcemic activities of Clodronic Acid.Investigational, Vet Approved
DiphenadioneClodronic Acid may increase the anticoagulant activities of Diphenadione.Experimental
DuloxetineDuloxetine may increase the antiplatelet activities of Clodronic Acid.Approved
EpimestrolClodronic Acid may increase the thrombogenic activities of Epimestrol.Experimental
EquileninThe risk or severity of adverse effects can be increased when Equilenin is combined with Clodronic Acid.Experimental
EquilinThe risk or severity of adverse effects can be increased when Equilin is combined with Clodronic Acid.Approved
EquolClodronic Acid may increase the thrombogenic activities of Equol.Investigational
EscitalopramEscitalopram may increase the antiplatelet activities of Clodronic Acid.Approved, Investigational
EsomeprazoleThe therapeutic efficacy of Clodronic Acid can be decreased when used in combination with Esomeprazole.Approved, Investigational
EstradiolClodronic Acid may increase the thrombogenic activities of Estradiol.Approved, Investigational, Vet Approved
Estradiol acetateClodronic Acid may increase the thrombogenic activities of Estradiol acetate.Approved, Investigational, Vet Approved
Estradiol cypionateClodronic Acid may increase the thrombogenic activities of Estradiol cypionate.Approved, Investigational, Vet Approved
Estradiol valerateClodronic Acid may increase the thrombogenic activities of Estradiol valerate.Approved, Investigational, Vet Approved
EstramustineThe serum concentration of Estramustine can be increased when it is combined with Clodronic Acid.Approved, Investigational
EstriolClodronic Acid may increase the thrombogenic activities of Estriol.Approved, Investigational, Vet Approved
Estrogens, esterifiedClodronic Acid may increase the thrombogenic activities of Estrogens, esterified.Approved
EstroneClodronic Acid may increase the thrombogenic activities of Estrone.Approved
Estrone sulfateThe risk or severity of adverse effects can be increased when Estrone sulfate is combined with Clodronic Acid.Approved
Ethinyl EstradiolClodronic Acid may increase the thrombogenic activities of Ethinyl Estradiol.Approved
Ethyl biscoumacetateClodronic Acid may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
EtoperidoneEtoperidone may increase the antiplatelet activities of Clodronic Acid.Withdrawn
FluasteroneThe risk or severity of adverse effects can be increased when Fluasterone is combined with Clodronic Acid.Investigational
FludrocortisoneThe risk or severity of adverse effects can be increased when Fludrocortisone is combined with Clodronic Acid.Approved, Investigational
FluindioneClodronic Acid may increase the anticoagulant activities of Fluindione.Approved, Investigational
FlumethasoneThe risk or severity of adverse effects can be increased when Flumethasone is combined with Clodronic Acid.Approved, Vet Approved
FlunisolideThe risk or severity of adverse effects can be increased when Flunisolide is combined with Clodronic Acid.Approved, Investigational
Fluocinolone AcetonideThe risk or severity of adverse effects can be increased when Fluocinolone Acetonide is combined with Clodronic Acid.Approved, Investigational, Vet Approved
FluocinonideThe risk or severity of adverse effects can be increased when Fluocinonide is combined with Clodronic Acid.Approved, Investigational
FluocortoloneThe risk or severity of adverse effects can be increased when Fluocortolone is combined with Clodronic Acid.Approved, Withdrawn
FluorometholoneThe risk or severity of adverse effects can be increased when Fluorometholone is combined with Clodronic Acid.Approved, Investigational
FluoxetineFluoxetine may increase the antiplatelet activities of Clodronic Acid.Approved, Vet Approved
FluprednideneThe risk or severity of adverse effects can be increased when Fluprednidene is combined with Clodronic Acid.Approved, Withdrawn
FluprednisoloneThe risk or severity of adverse effects can be increased when Fluprednisolone is combined with Clodronic Acid.Approved
FlurandrenolideThe risk or severity of adverse effects can be increased when Flurandrenolide is combined with Clodronic Acid.Approved
FluticasoneThe risk or severity of adverse effects can be increased when Fluticasone is combined with Clodronic Acid.Approved, Experimental, Investigational
Fluticasone furoateThe risk or severity of adverse effects can be increased when Fluticasone furoate is combined with Clodronic Acid.Approved
Fluticasone propionateThe risk or severity of adverse effects can be increased when Fluticasone propionate is combined with Clodronic Acid.Approved
FluvoxamineFluvoxamine may increase the antiplatelet activities of Clodronic Acid.Approved, Investigational
FormestaneThe risk or severity of adverse effects can be increased when Formestane is combined with Clodronic Acid.Approved, Investigational, Withdrawn
FramycetinFramycetin may increase the hypocalcemic activities of Clodronic Acid.Approved
GeneticinGeneticin may increase the hypocalcemic activities of Clodronic Acid.Experimental
GenisteinClodronic Acid may increase the thrombogenic activities of Genistein.Investigational
GentamicinGentamicin may increase the hypocalcemic activities of Clodronic Acid.Approved, Vet Approved
GENTAMICIN C1AGENTAMICIN C1A may increase the hypocalcemic activities of Clodronic Acid.Experimental
HalcinonideThe risk or severity of adverse effects can be increased when Halcinonide is combined with Clodronic Acid.Approved, Investigational, Withdrawn
HE3286The risk or severity of adverse effects can be increased when HE3286 is combined with Clodronic Acid.Investigational
HexestrolClodronic Acid may increase the thrombogenic activities of Hexestrol.Withdrawn
HydrocortisoneThe risk or severity of adverse effects can be increased when Hydrocortisone is combined with Clodronic Acid.Approved, Vet Approved
HydrotalciteThe serum concentration of Clodronic Acid can be decreased when it is combined with Hydrotalcite.Approved, Experimental, Investigational
Hygromycin BHygromycin B may increase the hypocalcemic activities of Clodronic Acid.Vet Approved
IndalpineIndalpine may increase the antiplatelet activities of Clodronic Acid.Investigational, Withdrawn
Iron saccharateThe serum concentration of Clodronic Acid can be decreased when it is combined with Iron saccharate.Approved
IsepamicinIsepamicin may increase the hypocalcemic activities of Clodronic Acid.Experimental
IstaroximeThe risk or severity of adverse effects can be increased when Istaroxime is combined with Clodronic Acid.Investigational
KanamycinKanamycin may increase the hypocalcemic activities of Clodronic Acid.Approved, Investigational, Vet Approved
LansoprazoleThe therapeutic efficacy of Clodronic Acid can be decreased when used in combination with Lansoprazole.Approved, Investigational
LevomilnacipranLevomilnacipran may increase the antiplatelet activities of Clodronic Acid.Approved, Investigational
LoteprednolThe risk or severity of adverse effects can be increased when Loteprednol is combined with Clodronic Acid.Approved
Magnesium carbonateThe serum concentration of Clodronic Acid can be decreased when it is combined with Magnesium carbonate.Approved, Investigational
Magnesium hydroxideThe serum concentration of Clodronic Acid can be decreased when it is combined with Magnesium hydroxide.Approved, Investigational
Magnesium oxideThe serum concentration of Clodronic Acid can be decreased when it is combined with Magnesium oxide.Approved
Magnesium peroxideThe serum concentration of Clodronic Acid can be decreased when it is combined with Magnesium peroxide.Experimental
Magnesium silicateThe serum concentration of Clodronic Acid can be decreased when it is combined with Magnesium silicate.Approved
Magnesium sulfateThe serum concentration of Clodronic Acid can be decreased when it is combined with Magnesium sulfate.Approved, Investigational, Vet Approved
Magnesium TrisilicateThe serum concentration of Clodronic Acid can be decreased when it is combined with Magnesium Trisilicate.Approved
ME-609The risk or severity of adverse effects can be increased when ME-609 is combined with Clodronic Acid.Investigational
MedrysoneThe risk or severity of adverse effects can be increased when Medrysone is combined with Clodronic Acid.Approved
MelengestrolThe risk or severity of adverse effects can be increased when Melengestrol is combined with Clodronic Acid.Vet Approved
MestranolClodronic Acid may increase the thrombogenic activities of Mestranol.Approved
MethallenestrilClodronic Acid may increase the thrombogenic activities of Methallenestril.Experimental
MethylprednisoloneThe risk or severity of adverse effects can be increased when Methylprednisolone is combined with Clodronic Acid.Approved, Vet Approved
MicronomicinMicronomicin may increase the hypocalcemic activities of Clodronic Acid.Experimental
MilnacipranMilnacipran may increase the antiplatelet activities of Clodronic Acid.Approved, Investigational
MometasoneThe risk or severity of adverse effects can be increased when Mometasone is combined with Clodronic Acid.Approved, Vet Approved
MoxestrolClodronic Acid may increase the thrombogenic activities of Moxestrol.Experimental
NCX 1022The risk or severity of adverse effects can be increased when NCX 1022 is combined with Clodronic Acid.Investigational
NeamineNeamine may increase the hypocalcemic activities of Clodronic Acid.Experimental
NefazodoneNefazodone may increase the antiplatelet activities of Clodronic Acid.Approved, Withdrawn
NeomycinNeomycin may increase the hypocalcemic activities of Clodronic Acid.Approved, Vet Approved
NetilmicinNetilmicin may increase the hypocalcemic activities of Clodronic Acid.Approved, Investigational
Oleoyl-estroneThe risk or severity of adverse effects can be increased when Oleoyl-estrone is combined with Clodronic Acid.Investigational
OmeprazoleThe therapeutic efficacy of Clodronic Acid can be decreased when used in combination with Omeprazole.Approved, Investigational, Vet Approved
PantoprazoleThe therapeutic efficacy of Clodronic Acid can be decreased when used in combination with Pantoprazole.Approved
ParamethasoneThe risk or severity of adverse effects can be increased when Paramethasone is combined with Clodronic Acid.Approved
ParomomycinParomomycin may increase the hypocalcemic activities of Clodronic Acid.Approved, Investigational
ParoxetineParoxetine may increase the antiplatelet activities of Clodronic Acid.Approved, Investigational
PhenindioneClodronic Acid may increase the anticoagulant activities of Phenindione.Approved, Investigational
PhenprocoumonClodronic Acid may increase the anticoagulant activities of Phenprocoumon.Approved, Investigational
PlazomicinPlazomicin may increase the hypocalcemic activities of Clodronic Acid.Investigational
Polyestradiol phosphateClodronic Acid may increase the thrombogenic activities of Polyestradiol phosphate.Approved
PrasteroneThe risk or severity of adverse effects can be increased when Prasterone is combined with Clodronic Acid.Approved, Investigational, Nutraceutical
Prasterone sulfateThe risk or severity of adverse effects can be increased when Prasterone sulfate is combined with Clodronic Acid.Investigational
PrednicarbateThe risk or severity of adverse effects can be increased when Prednicarbate is combined with Clodronic Acid.Approved, Investigational
PrednisoloneThe risk or severity of adverse effects can be increased when Prednisolone is combined with Clodronic Acid.Approved, Vet Approved
PrednisoneThe risk or severity of adverse effects can be increased when Prednisone is combined with Clodronic Acid.Approved, Vet Approved
PregnenoloneThe risk or severity of adverse effects can be increased when Pregnenolone is combined with Clodronic Acid.Approved, Experimental, Investigational
PromestrieneClodronic Acid may increase the thrombogenic activities of Promestriene.Investigational
PuromycinPuromycin may increase the hypocalcemic activities of Clodronic Acid.Experimental
QuinestrolClodronic Acid may increase the thrombogenic activities of Quinestrol.Approved
RabeprazoleThe therapeutic efficacy of Clodronic Acid can be decreased when used in combination with Rabeprazole.Approved, Investigational
RibostamycinRibostamycin may increase the hypocalcemic activities of Clodronic Acid.Approved, Investigational
RimexoloneThe risk or severity of adverse effects can be increased when Rimexolone is combined with Clodronic Acid.Approved
SecoisolariciresinolClodronic Acid may increase the thrombogenic activities of Secoisolariciresinol.Investigational
SertralineSertraline may increase the antiplatelet activities of Clodronic Acid.Approved
SisomicinSisomicin may increase the hypocalcemic activities of Clodronic Acid.Investigational
StreptomycinStreptomycin may increase the hypocalcemic activities of Clodronic Acid.Approved, Vet Approved
Synthetic Conjugated Estrogens, AClodronic Acid may increase the thrombogenic activities of Synthetic Conjugated Estrogens, A.Approved
Synthetic Conjugated Estrogens, BClodronic Acid may increase the thrombogenic activities of Synthetic Conjugated Estrogens, B.Approved
TiboloneClodronic Acid may increase the thrombogenic activities of Tibolone.Approved, Investigational
TioclomarolClodronic Acid may increase the anticoagulant activities of Tioclomarol.Experimental
TixocortolThe risk or severity of adverse effects can be increased when Tixocortol is combined with Clodronic Acid.Approved, Withdrawn
TobramycinTobramycin may increase the hypocalcemic activities of Clodronic Acid.Approved, Investigational
TriamcinoloneThe risk or severity of adverse effects can be increased when Triamcinolone is combined with Clodronic Acid.Approved, Vet Approved
TromethamineThe serum concentration of Clodronic Acid can be decreased when it is combined with Tromethamine.Approved
UlobetasolThe risk or severity of adverse effects can be increased when Ulobetasol is combined with Clodronic Acid.Approved
VenlafaxineVenlafaxine may increase the antiplatelet activities of Clodronic Acid.Approved
WarfarinClodronic Acid may increase the anticoagulant activities of Warfarin.Approved
ZeranolClodronic Acid may increase the thrombogenic activities of Zeranol.Vet Approved
ZimelidineZimelidine may increase the antiplatelet activities of Clodronic Acid.Withdrawn
Food Interactions
  • Food decreases absorption. Take on an empty stomach.

References

Synthesis Reference

Fritz Demmer, Berthold Stemmle, "Clodronate-containing medicaments and a process for the preparation thereof." U.S. Patent US4859472, issued September, 1980.

US4859472
General References
Not Available
External Links
Human Metabolome Database
HMDB0014858
PubChem Compound
25419
PubChem Substance
46508646
ChemSpider
23731
BindingDB
50216172
ChEBI
110423
ChEMBL
CHEMBL12318
Therapeutic Targets Database
DAP000564
PharmGKB
PA10239
Wikipedia
Clodronate
ATC Codes
M05BA02 — Clodronic acid
AHFS Codes
  • 92:24.00 — Bone Resorption Inhibitors
MSDS
Download (120 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Unknown StatusTreatmentAseptic Loosening of the Hip Prosthesis1
3Active Not RecruitingTreatmentCancer, Breast1
3CompletedTreatmentCancer, Breast1
3CompletedTreatmentPain / Prostate Cancer / Quality of Life1
3CompletedTreatmentPostmenopausal Osteoporosis (PMO)1
3CompletedTreatmentRadiation Induced Brachial Plexopathy1
Not AvailableCompletedNot AvailableBone Neoplasms1
Not AvailableCompletedNot AvailableMultiple Myeloma (MM) / Neoplasms, Breast / Osteolysis / Prostatic Neoplasms1
Not AvailableCompletedTreatmentBone destruction1
Not AvailableWithdrawnNot AvailableCancer, Breast1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionIntravenous60 mg
CapsuleOral400 mg
Prices
Unit descriptionCostUnit
Bonefos 60 mg/ml13.69USD ml
Bonefos 400 mg Capsule2.04USD capsule
Clasteon 400 mg Capsule1.36USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)250 °CPhysProp
water solubility395 mg/LNot Available
logP-2.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility7.47 mg/mLALOGPS
logP0.16ALOGPS
logP-0.067ChemAxon
logS-1.5ALOGPS
pKa (Strongest Acidic)0.62ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area115.06 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity38.21 m3·mol-1ChemAxon
Polarizability15.3 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8406
Blood Brain Barrier+0.9481
Caco-2 permeable-0.8956
P-glycoprotein substrateNon-substrate0.8597
P-glycoprotein inhibitor INon-inhibitor0.9701
P-glycoprotein inhibitor IINon-inhibitor0.9903
Renal organic cation transporterNon-inhibitor0.958
CYP450 2C9 substrateNon-substrate0.7693
CYP450 2D6 substrateNon-substrate0.8234
CYP450 3A4 substrateNon-substrate0.697
CYP450 1A2 substrateNon-inhibitor0.8539
CYP450 2C9 inhibitorNon-inhibitor0.8878
CYP450 2D6 inhibitorNon-inhibitor0.9091
CYP450 2C19 inhibitorNon-inhibitor0.8449
CYP450 3A4 inhibitorNon-inhibitor0.9061
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9743
Ames testNon AMES toxic0.7328
CarcinogenicityCarcinogens 0.6575
BiodegradationNot ready biodegradable0.927
Rat acute toxicity2.6142 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9321
hERG inhibition (predictor II)Non-inhibitor0.9427
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 / Organopnictogen compounds / Organophosphorus compounds / Organochlorides / Organic oxides / Hydrocarbon derivatives / Alkyl chlorides
Substituents
Bisphosphonate / Organophosphonic acid / Organic oxygen compound / Organopnictogen compound / Organic oxide / Hydrocarbon derivative / Organophosphorus compound / Organochloride / Organohalogen compound / Alkyl halide
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
one-carbon compound, organochlorine compound, 1,1-bis(phosphonic acid) (CHEBI:110423)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Adenine transmembrane transporter activity
Specific Function
Catalyzes the exchange of cytoplasmic ADP with mitochondrial ATP across the mitochondrial inner membrane.
Gene Name
SLC25A4
Uniprot ID
P12235
Uniprot Name
ADP/ATP translocase 1
Molecular Weight
33064.265 Da
References
  1. Lehenkari PP, Kellinsalmi M, Napankangas JP, Ylitalo KV, Monkkonen J, Rogers MJ, Azhayev A, Vaananen HK, Hassinen IE: Further insight into mechanism of action of clodronate: inhibition of mitochondrial ADP/ATP translocase by a nonhydrolyzable, adenine-containing metabolite. Mol Pharmacol. 2002 May;61(5):1255-62. [PubMed:11961144]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquitin protein ligase binding
Specific Function
Catalyzes the exchange of cytoplasmic ADP with mitochondrial ATP across the mitochondrial inner membrane. As part of the mitotic spindle-associated MMXD complex it may play a role in chromosome seg...
Gene Name
SLC25A5
Uniprot ID
P05141
Uniprot Name
ADP/ATP translocase 2
Molecular Weight
32851.965 Da
References
  1. Lehenkari PP, Kellinsalmi M, Napankangas JP, Ylitalo KV, Monkkonen J, Rogers MJ, Azhayev A, Vaananen HK, Hassinen IE: Further insight into mechanism of action of clodronate: inhibition of mitochondrial ADP/ATP translocase by a nonhydrolyzable, adenine-containing metabolite. Mol Pharmacol. 2002 May;61(5):1255-62. [PubMed:11961144]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Atp:adp antiporter activity
Specific Function
Catalyzes the exchange of cytoplasmic ADP with mitochondrial ATP across the mitochondrial inner membrane. May participate in the formation of the permeability transition pore complex (PTPC) respons...
Gene Name
SLC25A6
Uniprot ID
P12236
Uniprot Name
ADP/ATP translocase 3
Molecular Weight
32866.025 Da
References
  1. Lehenkari PP, Kellinsalmi M, Napankangas JP, Ylitalo KV, Monkkonen J, Rogers MJ, Azhayev A, Vaananen HK, Hassinen IE: Further insight into mechanism of action of clodronate: inhibition of mitochondrial ADP/ATP translocase by a nonhydrolyzable, adenine-containing metabolite. Mol Pharmacol. 2002 May;61(5):1255-62. [PubMed:11961144]
Kind
Small molecule
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
References
  1. Ganguli A, Steward C, Butler SL, Philips GJ, Meikle ST, Lloyd AW, Grant MH: Bacterial adhesion to bisphosphonate coated hydroxyapatite. J Mater Sci Mater Med. 2005 Apr;16(4):283-7. [PubMed:15803271]
  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]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Liu L, Igarashi K, Kanzaki H, Chiba M, Shinoda H, Mitani H: Clodronate inhibits PGE(2) production in compressed periodontal ligament cells. J Dent Res. 2006 Aug;85(8):757-60. [PubMed:16861295]

Drug created on June 13, 2005 07:24 / Updated on June 21, 2018 22:13