Jump to section
IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyClodronic Acid
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
Structure for DB00720 (Clodronic Acid)
- 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
Ingredient UNII CAS InChI Key Clodronate disodium N030400H8J 88416-50-6 XWHPUCFOTRBMGS-UHFFFAOYSA-L Clodronate disodium tetrahydrate Not Available Not Available Not applicable - Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Bonefos Solution 60 mg Intravenous Bayer 1992-12-31 Not applicable Canada 
Bonefos Capsule 400 mg Oral Bayer 1992-12-31 Not applicable Canada Clasteon Capsule 400 mg Oral Sunovion 2004-05-13 Not applicable Canada Ostac Cap 400mg Capsule 400 mg Oral Hoffmann La Roche 1994-12-31 2006-10-11 Canada - 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.
Target Actions Organism AADP/ATP translocase 1 inhibitorHuman AADP/ATP translocase 2 inhibitorHuman AADP/ATP translocase 3 inhibitorHuman AHydroxylapatite antagonistHuman - 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
Drug Interaction Drug group 16-Bromoepiandrosterone The risk or severity of adverse effects can be increased when 16-Bromoepiandrosterone is combined with Clodronic Acid. Investigational 19-norandrostenedione The risk or severity of adverse effects can be increased when 19-norandrostenedione is combined with Clodronic Acid. Experimental, Illicit 5-androstenedione The risk or severity of adverse effects can be increased when 5-androstenedione is combined with Clodronic Acid. Experimental, Illicit Acenocoumarol Clodronic Acid may increase the anticoagulant activities of Acenocoumarol. Approved, Investigational Alaproclate Alaproclate may increase the antiplatelet activities of Clodronic Acid. Experimental Alclometasone The risk or severity of adverse effects can be increased when Alclometasone is combined with Clodronic Acid. Approved Aldosterone The risk or severity of adverse effects can be increased when Aldosterone is combined with Clodronic Acid. Experimental, Investigational Almasilate The serum concentration of Clodronic Acid can be decreased when it is combined with Almasilate. Approved, Experimental Aloglutamol The serum concentration of Clodronic Acid can be decreased when it is combined with Aloglutamol. Approved Aluminium The serum concentration of Clodronic Acid can be decreased when it is combined with Aluminium. Approved, Investigational Aluminium acetoacetate The serum concentration of Clodronic Acid can be decreased when it is combined with Aluminium acetoacetate. Experimental Aluminium glycinate The serum concentration of Clodronic Acid can be decreased when it is combined with Aluminium glycinate. Experimental Aluminum hydroxide The serum concentration of Clodronic Acid can be decreased when it is combined with Aluminum hydroxide. Approved, Investigational Amcinonide The risk or severity of adverse effects can be increased when Amcinonide is combined with Clodronic Acid. Approved Amikacin Amikacin may increase the hypocalcemic activities of Clodronic Acid. Approved, Investigational, Vet Approved Androstenedione The risk or severity of adverse effects can be increased when Androstenedione is combined with Clodronic Acid. Experimental, Illicit Anecortave The risk or severity of adverse effects can be increased when Anecortave is combined with Clodronic Acid. Investigational anecortave acetate The risk or severity of adverse effects can be increased when anecortave acetate is combined with Clodronic Acid. Investigational Apramycin Apramycin may increase the hypocalcemic activities of Clodronic Acid. Experimental, Vet Approved Arbekacin Arbekacin may increase the hypocalcemic activities of Clodronic Acid. Approved, Investigational Atamestane The risk or severity of adverse effects can be increased when Atamestane is combined with Clodronic Acid. Investigational Bazedoxifene Clodronic Acid may increase the thrombogenic activities of Bazedoxifene. Approved, Investigational Beclomethasone dipropionate The risk or severity of adverse effects can be increased when Beclomethasone dipropionate is combined with Clodronic Acid. Approved, Investigational Bekanamycin Bekanamycin may increase the hypocalcemic activities of Clodronic Acid. Experimental Betamethasone The risk or severity of adverse effects can be increased when Betamethasone is combined with Clodronic Acid. Approved, Vet Approved Bismuth Subcitrate The serum concentration of Clodronic Acid can be decreased when it is combined with Bismuth Subcitrate. Approved, Investigational Bismuth subnitrate The serum concentration of Clodronic Acid can be decreased when it is combined with Bismuth subnitrate. Approved Budesonide The risk or severity of adverse effects can be increased when Budesonide is combined with Clodronic Acid. Approved Calcium Acetate The serum concentration of Clodronic Acid can be decreased when it is combined with Calcium Acetate. Approved, Investigational Calcium Carbonate The serum concentration of Clodronic Acid can be decreased when it is combined with Calcium Carbonate. Approved, Investigational Calcium Chloride The serum concentration of Clodronic Acid can be decreased when it is combined with Calcium Chloride. Approved Calcium Citrate The serum concentration of Clodronic Acid can be decreased when it is combined with Calcium Citrate. Approved Calcium glubionate The serum concentration of Clodronic Acid can be decreased when it is combined with Calcium glubionate. Approved Calcium Gluceptate The serum concentration of Clodronic Acid can be decreased when it is combined with Calcium Gluceptate. Approved Calcium gluconate The serum concentration of Clodronic Acid can be decreased when it is combined with Calcium gluconate. Approved, Vet Approved Calcium lactate The serum concentration of Clodronic Acid can be decreased when it is combined with Calcium lactate. Approved, Investigational, Vet Approved Calcium lactate gluconate The serum concentration of Clodronic Acid can be decreased when it is combined with Calcium lactate gluconate. Experimental Calcium levulinate The serum concentration of Clodronic Acid can be decreased when it is combined with Calcium levulinate. Approved, Experimental Calcium pangamate The serum concentration of Clodronic Acid can be decreased when it is combined with Calcium pangamate. Experimental Calcium Phosphate The serum concentration of Clodronic Acid can be decreased when it is combined with Calcium Phosphate. Approved Calcium silicate The serum concentration of Clodronic Acid can be decreased when it is combined with Calcium silicate. Experimental Casein The serum concentration of Clodronic Acid can be decreased when it is combined with Casein. Approved Chlorotrianisene Clodronic Acid may increase the thrombogenic activities of Chlorotrianisene. Investigational, Withdrawn Ciclesonide The risk or severity of adverse effects can be increased when Ciclesonide is combined with Clodronic Acid. Approved, Investigational Citalopram Citalopram may increase the antiplatelet activities of Clodronic Acid. Approved Clobetasol The risk or severity of adverse effects can be increased when Clobetasol is combined with Clodronic Acid. Approved, Investigational Clobetasol propionate The risk or severity of adverse effects can be increased when Clobetasol propionate is combined with Clodronic Acid. Approved Clobetasone The risk or severity of adverse effects can be increased when Clobetasone is combined with Clodronic Acid. Approved Clocortolone The risk or severity of adverse effects can be increased when Clocortolone is combined with Clodronic Acid. Approved Clorindione Clodronic Acid may increase the anticoagulant activities of Clorindione. Experimental Conjugated estrogens Clodronic Acid may increase the thrombogenic activities of Conjugated estrogens. Approved Cortexolone 17α-propionate The risk or severity of adverse effects can be increased when Cortexolone 17α-propionate is combined with Clodronic Acid. Investigational Corticosterone The risk or severity of adverse effects can be increased when Corticosterone is combined with Clodronic Acid. Experimental Cortisone acetate The risk or severity of adverse effects can be increased when Cortisone acetate is combined with Clodronic Acid. Approved, Investigational Daidzein Clodronic Acid may increase the thrombogenic activities of Daidzein. Experimental Dapoxetine Dapoxetine may increase the antiplatelet activities of Clodronic Acid. Investigational Deferasirox The risk or severity of adverse effects can be increased when Clodronic Acid is combined with Deferasirox. Approved, Investigational Deflazacort The risk or severity of adverse effects can be increased when Deflazacort is combined with Clodronic Acid. Approved, Investigational Desonide The risk or severity of adverse effects can be increased when Desonide is combined with Clodronic Acid. Approved, Investigational Desoximetasone The risk or severity of adverse effects can be increased when Desoximetasone is combined with Clodronic Acid. Approved Desoxycorticosterone acetate The risk or severity of adverse effects can be increased when Desoxycorticosterone acetate is combined with Clodronic Acid. Approved Desoxycorticosterone Pivalate The risk or severity of adverse effects can be increased when Desoxycorticosterone Pivalate is combined with Clodronic Acid. Experimental, Vet Approved Desvenlafaxine Desvenlafaxine may increase the antiplatelet activities of Clodronic Acid. Approved, Investigational Dexamethasone The risk or severity of adverse effects can be increased when Dexamethasone is combined with Clodronic Acid. Approved, Investigational, Vet Approved Dexamethasone isonicotinate The risk or severity of adverse effects can be increased when Dexamethasone isonicotinate is combined with Clodronic Acid. Vet Approved Dexlansoprazole The therapeutic efficacy of Clodronic Acid can be decreased when used in combination with Dexlansoprazole. Approved, Investigational Dexrabeprazole The therapeutic efficacy of Clodronic Acid can be decreased when used in combination with Dexrabeprazole. Experimental Dibekacin Dibekacin may increase the hypocalcemic activities of Clodronic Acid. Experimental Dicoumarol Clodronic Acid may increase the anticoagulant activities of Dicoumarol. Approved Dienestrol Clodronic Acid may increase the thrombogenic activities of Dienestrol. Approved, Investigational Diethylstilbestrol Clodronic Acid may increase the thrombogenic activities of Diethylstilbestrol. Approved, Investigational Diflorasone The risk or severity of adverse effects can be increased when Diflorasone is combined with Clodronic Acid. Approved Difluocortolone The risk or severity of adverse effects can be increased when Difluocortolone is combined with Clodronic Acid. Approved, Investigational, Withdrawn Difluprednate The risk or severity of adverse effects can be increased when Difluprednate is combined with Clodronic Acid. Approved Dihydrostreptomycin Dihydrostreptomycin may increase the hypocalcemic activities of Clodronic Acid. Investigational, Vet Approved Diphenadione Clodronic Acid may increase the anticoagulant activities of Diphenadione. Experimental Duloxetine Duloxetine may increase the antiplatelet activities of Clodronic Acid. Approved Epimestrol Clodronic Acid may increase the thrombogenic activities of Epimestrol. Experimental Equilenin The risk or severity of adverse effects can be increased when Equilenin is combined with Clodronic Acid. Experimental Equilin The risk or severity of adverse effects can be increased when Equilin is combined with Clodronic Acid. Approved Equol Clodronic Acid may increase the thrombogenic activities of Equol. Investigational Escitalopram Escitalopram may increase the antiplatelet activities of Clodronic Acid. Approved, Investigational Esomeprazole The therapeutic efficacy of Clodronic Acid can be decreased when used in combination with Esomeprazole. Approved, Investigational Estradiol Clodronic Acid may increase the thrombogenic activities of Estradiol. Approved, Investigational, Vet Approved Estradiol acetate Clodronic Acid may increase the thrombogenic activities of Estradiol acetate. Approved, Investigational, Vet Approved Estradiol cypionate Clodronic Acid may increase the thrombogenic activities of Estradiol cypionate. Approved, Investigational, Vet Approved Estradiol valerate Clodronic Acid may increase the thrombogenic activities of Estradiol valerate. Approved, Investigational, Vet Approved Estramustine The serum concentration of Estramustine can be increased when it is combined with Clodronic Acid. Approved, Investigational Estriol Clodronic Acid may increase the thrombogenic activities of Estriol. Approved, Investigational, Vet Approved Estrogens, esterified Clodronic Acid may increase the thrombogenic activities of Estrogens, esterified. Approved Estrone Clodronic Acid may increase the thrombogenic activities of Estrone. Approved Estrone sulfate The risk or severity of adverse effects can be increased when Estrone sulfate is combined with Clodronic Acid. Approved Ethinyl Estradiol Clodronic Acid may increase the thrombogenic activities of Ethinyl Estradiol. Approved Ethyl biscoumacetate Clodronic Acid may increase the anticoagulant activities of Ethyl biscoumacetate. Withdrawn Etoperidone Etoperidone may increase the antiplatelet activities of Clodronic Acid. Withdrawn Fluasterone The risk or severity of adverse effects can be increased when Fluasterone is combined with Clodronic Acid. Investigational Fludrocortisone The risk or severity of adverse effects can be increased when Fludrocortisone is combined with Clodronic Acid. Approved, Investigational Fluindione Clodronic Acid may increase the anticoagulant activities of Fluindione. Approved, Investigational Flumethasone The risk or severity of adverse effects can be increased when Flumethasone is combined with Clodronic Acid. Approved, Vet Approved Flunisolide The risk or severity of adverse effects can be increased when Flunisolide is combined with Clodronic Acid. Approved, Investigational Fluocinolone Acetonide The risk or severity of adverse effects can be increased when Fluocinolone Acetonide is combined with Clodronic Acid. Approved, Investigational, Vet Approved Fluocinonide The risk or severity of adverse effects can be increased when Fluocinonide is combined with Clodronic Acid. Approved, Investigational Fluocortolone The risk or severity of adverse effects can be increased when Fluocortolone is combined with Clodronic Acid. Approved, Withdrawn Fluorometholone The risk or severity of adverse effects can be increased when Fluorometholone is combined with Clodronic Acid. Approved, Investigational Fluoxetine Fluoxetine may increase the antiplatelet activities of Clodronic Acid. Approved, Vet Approved Fluprednidene The risk or severity of adverse effects can be increased when Fluprednidene is combined with Clodronic Acid. Approved, Withdrawn Fluprednisolone The risk or severity of adverse effects can be increased when Fluprednisolone is combined with Clodronic Acid. Approved Flurandrenolide The risk or severity of adverse effects can be increased when Flurandrenolide is combined with Clodronic Acid. Approved Fluticasone The risk or severity of adverse effects can be increased when Fluticasone is combined with Clodronic Acid. Approved, Experimental, Investigational Fluticasone furoate The risk or severity of adverse effects can be increased when Fluticasone furoate is combined with Clodronic Acid. Approved Fluticasone propionate The risk or severity of adverse effects can be increased when Fluticasone propionate is combined with Clodronic Acid. Approved Fluvoxamine Fluvoxamine may increase the antiplatelet activities of Clodronic Acid. Approved, Investigational Formestane The risk or severity of adverse effects can be increased when Formestane is combined with Clodronic Acid. Approved, Investigational, Withdrawn Framycetin Framycetin may increase the hypocalcemic activities of Clodronic Acid. Approved Geneticin Geneticin may increase the hypocalcemic activities of Clodronic Acid. Experimental Genistein Clodronic Acid may increase the thrombogenic activities of Genistein. Investigational Gentamicin Gentamicin may increase the hypocalcemic activities of Clodronic Acid. Approved, Vet Approved GENTAMICIN C1A GENTAMICIN C1A may increase the hypocalcemic activities of Clodronic Acid. Experimental Halcinonide The risk or severity of adverse effects can be increased when Halcinonide is combined with Clodronic Acid. Approved, Investigational, Withdrawn HE3286 The risk or severity of adverse effects can be increased when HE3286 is combined with Clodronic Acid. Investigational Hexestrol Clodronic Acid may increase the thrombogenic activities of Hexestrol. Withdrawn Hydrocortisone The risk or severity of adverse effects can be increased when Hydrocortisone is combined with Clodronic Acid. Approved, Vet Approved Hydrotalcite The serum concentration of Clodronic Acid can be decreased when it is combined with Hydrotalcite. Approved, Experimental, Investigational Hygromycin B Hygromycin B may increase the hypocalcemic activities of Clodronic Acid. Vet Approved Indalpine Indalpine may increase the antiplatelet activities of Clodronic Acid. Investigational, Withdrawn Iron saccharate The serum concentration of Clodronic Acid can be decreased when it is combined with Iron saccharate. Approved Isepamicin Isepamicin may increase the hypocalcemic activities of Clodronic Acid. Experimental Istaroxime The risk or severity of adverse effects can be increased when Istaroxime is combined with Clodronic Acid. Investigational Kanamycin Kanamycin may increase the hypocalcemic activities of Clodronic Acid. Approved, Investigational, Vet Approved Lansoprazole The therapeutic efficacy of Clodronic Acid can be decreased when used in combination with Lansoprazole. Approved, Investigational Levomilnacipran Levomilnacipran may increase the antiplatelet activities of Clodronic Acid. Approved, Investigational Loteprednol The risk or severity of adverse effects can be increased when Loteprednol is combined with Clodronic Acid. Approved Magnesium carbonate The serum concentration of Clodronic Acid can be decreased when it is combined with Magnesium carbonate. Approved, Investigational Magnesium hydroxide The serum concentration of Clodronic Acid can be decreased when it is combined with Magnesium hydroxide. Approved, Investigational Magnesium oxide The serum concentration of Clodronic Acid can be decreased when it is combined with Magnesium oxide. Approved Magnesium peroxide The serum concentration of Clodronic Acid can be decreased when it is combined with Magnesium peroxide. Experimental Magnesium silicate The serum concentration of Clodronic Acid can be decreased when it is combined with Magnesium silicate. Approved Magnesium sulfate The serum concentration of Clodronic Acid can be decreased when it is combined with Magnesium sulfate. Approved, Investigational, Vet Approved Magnesium Trisilicate The serum concentration of Clodronic Acid can be decreased when it is combined with Magnesium Trisilicate. Approved ME-609 The risk or severity of adverse effects can be increased when ME-609 is combined with Clodronic Acid. Investigational Medrysone The risk or severity of adverse effects can be increased when Medrysone is combined with Clodronic Acid. Approved Melengestrol The risk or severity of adverse effects can be increased when Melengestrol is combined with Clodronic Acid. Vet Approved Mestranol Clodronic Acid may increase the thrombogenic activities of Mestranol. Approved Methallenestril Clodronic Acid may increase the thrombogenic activities of Methallenestril. Experimental Methylprednisolone The risk or severity of adverse effects can be increased when Methylprednisolone is combined with Clodronic Acid. Approved, Vet Approved Micronomicin Micronomicin may increase the hypocalcemic activities of Clodronic Acid. Experimental Milnacipran Milnacipran may increase the antiplatelet activities of Clodronic Acid. Approved, Investigational Mometasone The risk or severity of adverse effects can be increased when Mometasone is combined with Clodronic Acid. Approved, Vet Approved Moxestrol Clodronic Acid may increase the thrombogenic activities of Moxestrol. Experimental NCX 1022 The risk or severity of adverse effects can be increased when NCX 1022 is combined with Clodronic Acid. Investigational Neamine Neamine may increase the hypocalcemic activities of Clodronic Acid. Experimental Nefazodone Nefazodone may increase the antiplatelet activities of Clodronic Acid. Approved, Withdrawn Neomycin Neomycin may increase the hypocalcemic activities of Clodronic Acid. Approved, Vet Approved Netilmicin Netilmicin may increase the hypocalcemic activities of Clodronic Acid. Approved, Investigational Oleoyl-estrone The risk or severity of adverse effects can be increased when Oleoyl-estrone is combined with Clodronic Acid. Investigational Omeprazole The therapeutic efficacy of Clodronic Acid can be decreased when used in combination with Omeprazole. Approved, Investigational, Vet Approved Pantoprazole The therapeutic efficacy of Clodronic Acid can be decreased when used in combination with Pantoprazole. Approved Paramethasone The risk or severity of adverse effects can be increased when Paramethasone is combined with Clodronic Acid. Approved Paromomycin Paromomycin may increase the hypocalcemic activities of Clodronic Acid. Approved, Investigational Paroxetine Paroxetine may increase the antiplatelet activities of Clodronic Acid. Approved, Investigational Phenindione Clodronic Acid may increase the anticoagulant activities of Phenindione. Approved, Investigational Phenprocoumon Clodronic Acid may increase the anticoagulant activities of Phenprocoumon. Approved, Investigational Plazomicin Plazomicin may increase the hypocalcemic activities of Clodronic Acid. Investigational Polyestradiol phosphate Clodronic Acid may increase the thrombogenic activities of Polyestradiol phosphate. Approved Prasterone The risk or severity of adverse effects can be increased when Prasterone is combined with Clodronic Acid. Approved, Investigational, Nutraceutical Prasterone sulfate The risk or severity of adverse effects can be increased when Prasterone sulfate is combined with Clodronic Acid. Investigational Prednicarbate The risk or severity of adverse effects can be increased when Prednicarbate is combined with Clodronic Acid. Approved, Investigational Prednisolone The risk or severity of adverse effects can be increased when Prednisolone is combined with Clodronic Acid. Approved, Vet Approved Prednisone The risk or severity of adverse effects can be increased when Prednisone is combined with Clodronic Acid. Approved, Vet Approved Pregnenolone The risk or severity of adverse effects can be increased when Pregnenolone is combined with Clodronic Acid. Approved, Experimental, Investigational Promestriene Clodronic Acid may increase the thrombogenic activities of Promestriene. Investigational Puromycin Puromycin may increase the hypocalcemic activities of Clodronic Acid. Experimental Quinestrol Clodronic Acid may increase the thrombogenic activities of Quinestrol. Approved Rabeprazole The therapeutic efficacy of Clodronic Acid can be decreased when used in combination with Rabeprazole. Approved, Investigational Ribostamycin Ribostamycin may increase the hypocalcemic activities of Clodronic Acid. Approved, Investigational Rimexolone The risk or severity of adverse effects can be increased when Rimexolone is combined with Clodronic Acid. Approved Secoisolariciresinol Clodronic Acid may increase the thrombogenic activities of Secoisolariciresinol. Investigational Sertraline Sertraline may increase the antiplatelet activities of Clodronic Acid. Approved Sisomicin Sisomicin may increase the hypocalcemic activities of Clodronic Acid. Investigational Streptomycin Streptomycin may increase the hypocalcemic activities of Clodronic Acid. Approved, Vet Approved Synthetic Conjugated Estrogens, A Clodronic Acid may increase the thrombogenic activities of Synthetic Conjugated Estrogens, A. Approved Synthetic Conjugated Estrogens, B Clodronic Acid may increase the thrombogenic activities of Synthetic Conjugated Estrogens, B. Approved Tibolone Clodronic Acid may increase the thrombogenic activities of Tibolone. Approved, Investigational Tioclomarol Clodronic Acid may increase the anticoagulant activities of Tioclomarol. Experimental Tixocortol The risk or severity of adverse effects can be increased when Tixocortol is combined with Clodronic Acid. Approved, Withdrawn Tobramycin Tobramycin may increase the hypocalcemic activities of Clodronic Acid. Approved, Investigational Triamcinolone The risk or severity of adverse effects can be increased when Triamcinolone is combined with Clodronic Acid. Approved, Vet Approved Tromethamine The serum concentration of Clodronic Acid can be decreased when it is combined with Tromethamine. Approved Ulobetasol The risk or severity of adverse effects can be increased when Ulobetasol is combined with Clodronic Acid. Approved Venlafaxine Venlafaxine may increase the antiplatelet activities of Clodronic Acid. Approved Warfarin Clodronic Acid may increase the anticoagulant activities of Warfarin. Approved Zeranol Clodronic Acid may increase the thrombogenic activities of Zeranol. Vet Approved Zimelidine Zimelidine 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
Phase Status Purpose Conditions Count 2 Unknown Status Treatment Aseptic Loosening of the Hip Prosthesis 1 3 Active Not Recruiting Treatment Cancer, Breast 1 3 Completed Treatment Cancer, Breast 1 3 Completed Treatment Pain / Prostate Cancer / Quality of Life 1 3 Completed Treatment Postmenopausal Osteoporosis (PMO) 1 3 Completed Treatment Radiation Induced Brachial Plexopathy 1 Not Available Completed Not Available Bone Neoplasms 1 Not Available Completed Not Available Multiple Myeloma (MM) / Neoplasms, Breast / Osteolysis / Prostatic Neoplasms 1 Not Available Completed Treatment Bone destruction 1 Not Available Withdrawn Not Available Cancer, Breast 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage forms
Form Route Strength Solution Intravenous 60 mg Capsule Oral 400 mg - Prices
Unit description Cost Unit Bonefos 60 mg/ml 13.69USD ml Bonefos 400 mg Capsule 2.04USD capsule Clasteon 400 mg Capsule 1.36USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 250 °C PhysProp water solubility 395 mg/L Not Available logP -2.4 Not Available - Predicted Properties
Property Value Source Water Solubility 7.47 mg/mL ALOGPS logP 0.16 ALOGPS logP -0.067 ChemAxon logS -1.5 ALOGPS pKa (Strongest Acidic) 0.62 ChemAxon Physiological Charge -2 ChemAxon Hydrogen Acceptor Count 6 ChemAxon Hydrogen Donor Count 4 ChemAxon Polar Surface Area 115.06 Å2 ChemAxon Rotatable Bond Count 2 ChemAxon Refractivity 38.21 m3·mol-1 ChemAxon Polarizability 15.3 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 - 0.8406 Blood Brain Barrier + 0.9481 Caco-2 permeable - 0.8956 P-glycoprotein substrate Non-substrate 0.8597 P-glycoprotein inhibitor I Non-inhibitor 0.9701 P-glycoprotein inhibitor II Non-inhibitor 0.9903 Renal organic cation transporter Non-inhibitor 0.958 CYP450 2C9 substrate Non-substrate 0.7693 CYP450 2D6 substrate Non-substrate 0.8234 CYP450 3A4 substrate Non-substrate 0.697 CYP450 1A2 substrate Non-inhibitor 0.8539 CYP450 2C9 inhibitor Non-inhibitor 0.8878 CYP450 2D6 inhibitor Non-inhibitor 0.9091 CYP450 2C19 inhibitor Non-inhibitor 0.8449 CYP450 3A4 inhibitor Non-inhibitor 0.9061 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9743 Ames test Non AMES toxic 0.7328 Carcinogenicity Carcinogens 0.6575 Biodegradation Not ready biodegradable 0.927 Rat acute toxicity 2.6142 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9321 hERG inhibition (predictor II) Non-inhibitor 0.9427
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 / 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
- 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]
- 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
- 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
- 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]
Yes
Antagonist
References
- 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]
- 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
- 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