Identification

Name
Tiludronic acid
Accession Number
DB01133  (APRD01259)
Type
Small Molecule
Groups
Approved, Investigational, Vet Approved
Description

Tiludronic acid is a bisphosphonate characterized by a (4-chlorophenylthio) group on the carbon atom of the basic P-C-P structure common to all bisphosphonates.

Structure
Thumb
Synonyms
  • Acide tiludronique
  • Acido tiludronico
  • Acidum tiludronicum
  • Tiludronate
External IDs
SR 41319 / SR-41319
Product Ingredients
IngredientUNIICASInChI Key
Tiludronate DisodiumBH6M93CIA0149845-07-8SKUHWSDHMJMHIW-UHFFFAOYSA-L
International/Other Brands
Skelid
Categories
UNII
6PNS59HP4Y
CAS number
89987-06-4
Weight
Average: 318.608
Monoisotopic: 317.928359441
Chemical Formula
C7H9ClO6P2S
InChI Key
DKJJVAGXPKPDRL-UHFFFAOYSA-N
InChI
InChI=1S/C7H9ClO6P2S/c8-5-1-3-6(4-2-5)17-7(15(9,10)11)16(12,13)14/h1-4,7H,(H2,9,10,11)(H2,12,13,14)
IUPAC Name
{[(4-chlorophenyl)sulfanyl](phosphono)methyl}phosphonic acid
SMILES
OP(O)(=O)C(SC1=CC=C(Cl)C=C1)P(O)(O)=O

Pharmacology

Indication

For treatment of Paget's disease of bone (osteitis deformans).

Structured Indications
Not Available
Pharmacodynamics

Tiludronate is a first generation (non-nitrogenous) bisphosphonate in the same family as etidronate and clodronate. Tiludronate affects calcium metabolism and inhibits bone resorption and soft tissue calcification. Of the tiludronate 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.

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. In vitro studies indicate that tiludronate acts primarily on bone through a mechanism that involves inhibition of osteoclastic activity with a probable reduction in the enzymatic and transport processes that lead to resorption of the mineralized matrix. Bone resorption occurs following recruitment, activation, and polarization of osteoclasts. Tiludronate appears to inhibit osteoclasts by at least two mechanisms: disruption of the cytoskeletal ring structure, possibly by inhibition of protein-tyrosine-phosphatase, thus leading to detachment of osteoclasts from the bone surface and the inhibition of the osteoclastic proton pump.

TargetActionsOrganism
AAdenosine triphosphate (ATP)
inhibitor
Human
AHydroxylapatite
antagonist
Human
UV-type proton ATPase catalytic subunit A
inhibitor
Human
UTyrosine-protein phosphatase non-receptor type 1
inhibitor
Human
Absorption

The mean oral bioavailability in healthy male subjects is 6% after an oral dose equivalent to 400 mg tiludronic acid administered after an overnight fast and 4 hours before a standard breakfast. In single-dose studies, bioavailability was reduced by 90% when an oral dose equivalent to 400 mg tiludronic acid was administered with, or 2 hours after, a standard breakfast compared to the same dose administered after an overnight fast and 4 hours before a standard breakfast.

Volume of distribution
Not Available
Protein binding

Approximately 90% bound to human serum protein (mainly albumin) at plasma concentrations between 1 and 10 mg/L.

Metabolism

In vitro, tiludronic acid is not metabolized in human liver microsomes and hepatocytes. There is no evidence that tiludronate is metabolized in humans.

Route of elimination

The principal route of elimination of tiludronic acid is in the urine.

Half life

Half-life in healthy subjects is 50 hours following administration of a 400 mg single oral dose. Half-life in pagetic patients is about 150 hours following administration of 400 mg tiludronate a day for 12 days. In patients with renal insufficiency (creatinine clearance between 11 and 18 mL per minute [mL/min]), half-life is 205 hours from plasma after administration of a single, oral dose equivalent to 400 mg tiludronate.

Clearance
  • renal cl=10 mL/min [IV administration of 20-mg dose]
Toxicity

Based on the known action of tiludronate, hypocalcemia is a potential consequence of overdose. In one patient with hypercalcemia of malignancy, intravenous administration of high doses (800 mg/day total dose, 6 mg/kg/day for 2 days) was associated with acute renal failure and death.

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

Interactions

Drug Interactions
DrugInteractionDrug group
AceclofenacThe risk or severity of adverse effects can be increased when Aceclofenac is combined with Tiludronic acid.Approved, Investigational
AcemetacinThe risk or severity of adverse effects can be increased when Acemetacin is combined with Tiludronic acid.Approved, Experimental, Investigational
Acetylsalicylic acidThe serum concentration of Tiludronic acid can be decreased when it is combined with Acetylsalicylic acid.Approved, Vet Approved
AclarubicinAclarubicin may increase the hypocalcemic activities of Tiludronic acid.Investigational
AdapaleneThe risk or severity of adverse effects can be increased when Adapalene is combined with Tiludronic acid.Approved
AlclofenacThe risk or severity of adverse effects can be increased when Alclofenac is combined with Tiludronic acid.Approved, Withdrawn
AldoxorubicinAldoxorubicin may increase the hypocalcemic activities of Tiludronic acid.Investigational
AlmasilateThe serum concentration of Tiludronic acid can be decreased when it is combined with Almasilate.Approved, Experimental
AlminoprofenThe risk or severity of adverse effects can be increased when Alminoprofen is combined with Tiludronic acid.Experimental
AloglutamolThe serum concentration of Tiludronic acid can be decreased when it is combined with Aloglutamol.Experimental
AluminiumThe serum concentration of Tiludronic acid can be decreased when it is combined with Aluminium.Approved
Aluminium acetoacetateThe serum concentration of Tiludronic acid can be decreased when it is combined with Aluminium acetoacetate.Experimental
Aluminium glycinateThe serum concentration of Tiludronic acid can be decreased when it is combined with Aluminium glycinate.Experimental
Aluminum hydroxideThe serum concentration of Tiludronic acid can be decreased when it is combined with Aluminum hydroxide.Approved
AmikacinAmikacin may increase the hypocalcemic activities of Tiludronic acid.Approved, Vet Approved
AmrubicinAmrubicin may increase the hypocalcemic activities of Tiludronic acid.Approved, Investigational
AndrographolideThe risk or severity of adverse effects can be increased when Andrographolide is combined with Tiludronic acid.Investigational
AnisodamineThe risk or severity of adverse effects can be increased when Anisodamine is combined with Tiludronic acid.Investigational
AnnamycinAnnamycin may increase the hypocalcemic activities of Tiludronic acid.Investigational
AntipyrineThe risk or severity of adverse effects can be increased when Antipyrine is combined with Tiludronic acid.Approved
ApocyninThe risk or severity of adverse effects can be increased when Apocynin is combined with Tiludronic acid.Investigational
ApramycinApramycin may increase the hypocalcemic activities of Tiludronic acid.Experimental, Vet Approved
ApremilastThe risk or severity of adverse effects can be increased when Apremilast is combined with Tiludronic acid.Approved, Investigational
ArbekacinArbekacin may increase the hypocalcemic activities of Tiludronic acid.Approved, Investigational
AzapropazoneThe risk or severity of adverse effects can be increased when Azapropazone is combined with Tiludronic acid.Withdrawn
AzelastineThe risk or severity of adverse effects can be increased when Azelastine is combined with Tiludronic acid.Approved
BalsalazideThe risk or severity of adverse effects can be increased when Balsalazide is combined with Tiludronic acid.Approved, Investigational
BekanamycinBekanamycin may increase the hypocalcemic activities of Tiludronic acid.Experimental
BendazacThe risk or severity of adverse effects can be increased when Bendazac is combined with Tiludronic acid.Experimental
BenorilateThe risk or severity of adverse effects can be increased when Benorilate is combined with Tiludronic acid.Experimental
BenoxaprofenThe risk or severity of adverse effects can be increased when Benoxaprofen is combined with Tiludronic acid.Withdrawn
BenzydamineThe risk or severity of adverse effects can be increased when Benzydamine is combined with Tiludronic acid.Approved
BevoniumThe risk or severity of adverse effects can be increased when Bevonium is combined with Tiludronic acid.Experimental
Bismuth SubcitrateThe serum concentration of Tiludronic acid can be decreased when it is combined with Bismuth Subcitrate.Approved
Bismuth subnitrateThe serum concentration of Tiludronic acid can be decreased when it is combined with Bismuth subnitrate.Experimental
BromfenacThe risk or severity of adverse effects can be increased when Bromfenac is combined with Tiludronic acid.Approved
BucillamineThe risk or severity of adverse effects can be increased when Bucillamine is combined with Tiludronic acid.Investigational
BufexamacThe risk or severity of adverse effects can be increased when Bufexamac is combined with Tiludronic acid.Experimental
BumadizoneThe risk or severity of adverse effects can be increased when Bumadizone is combined with Tiludronic acid.Experimental
Calcium AcetateThe serum concentration of Tiludronic acid can be decreased when it is combined with Calcium Acetate.Approved
Calcium CarbonateThe serum concentration of Tiludronic acid can be decreased when it is combined with Calcium Carbonate.Approved
Calcium ChlorideThe serum concentration of Tiludronic acid can be decreased when it is combined with Calcium Chloride.Approved
Calcium CitrateThe serum concentration of Tiludronic acid can be decreased when it is combined with Calcium Citrate.Approved
Calcium glubionateThe serum concentration of Tiludronic acid can be decreased when it is combined with Calcium glubionate.Approved
Calcium GluceptateThe serum concentration of Tiludronic acid can be decreased when it is combined with Calcium Gluceptate.Approved
Calcium gluconateThe serum concentration of Tiludronic acid can be decreased when it is combined with Calcium gluconate.Approved, Vet Approved
Calcium lactateThe serum concentration of Tiludronic acid can be decreased when it is combined with Calcium lactate.Approved, Experimental, Investigational, Vet Approved
Calcium lactate gluconateThe serum concentration of Tiludronic acid can be decreased when it is combined with Calcium lactate gluconate.Experimental
Calcium laevulateThe serum concentration of Tiludronic acid can be decreased when it is combined with Calcium laevulate.Experimental
Calcium pangamateThe serum concentration of Tiludronic acid can be decreased when it is combined with Calcium pangamate.Experimental
Calcium PhosphateThe serum concentration of Tiludronic acid can be decreased when it is combined with Calcium Phosphate.Approved
Calcium silicateThe serum concentration of Tiludronic acid can be decreased when it is combined with Calcium silicate.Experimental
Carbaspirin calciumThe risk or severity of adverse effects can be increased when Carbaspirin calcium is combined with Tiludronic acid.Experimental, Investigational
CarprofenThe risk or severity of adverse effects can be increased when Carprofen is combined with Tiludronic acid.Approved, Vet Approved, Withdrawn
CaseinThe serum concentration of Tiludronic acid can be decreased when it is combined with Casein.Approved
CastanospermineThe risk or severity of adverse effects can be increased when Castanospermine is combined with Tiludronic acid.Experimental
CelecoxibThe risk or severity of adverse effects can be increased when Celecoxib is combined with Tiludronic acid.Approved, Investigational
ChloroquineThe risk or severity of adverse effects can be increased when Chloroquine is combined with Tiludronic acid.Approved, Vet Approved
Choline magnesium trisalicylateThe risk or severity of adverse effects can be increased when Choline magnesium trisalicylate is combined with Tiludronic acid.Approved
ClonixinThe risk or severity of adverse effects can be increased when Clonixin is combined with Tiludronic acid.Approved
CurcuminThe risk or severity of adverse effects can be increased when Curcumin is combined with Tiludronic acid.Investigational
DaunorubicinDaunorubicin may increase the hypocalcemic activities of Tiludronic acid.Approved
DeferasiroxThe risk or severity of adverse effects can be increased when Tiludronic acid is combined with Deferasirox.Approved, Investigational
DexlansoprazoleThe therapeutic efficacy of Tiludronic acid can be decreased when used in combination with Dexlansoprazole.Approved
DexrabeprazoleThe therapeutic efficacy of Tiludronic acid can be decreased when used in combination with Dexrabeprazole.Experimental
DibekacinDibekacin may increase the hypocalcemic activities of Tiludronic acid.Experimental
DiclofenacThe risk or severity of adverse effects can be increased when Diclofenac is combined with Tiludronic acid.Approved, Vet Approved
DifenpiramideThe risk or severity of adverse effects can be increased when Difenpiramide is combined with Tiludronic acid.Experimental
DiflunisalThe risk or severity of adverse effects can be increased when Diflunisal is combined with Tiludronic acid.Approved
DihydrostreptomycinDihydrostreptomycin may increase the hypocalcemic activities of Tiludronic acid.Investigational, Vet Approved
DoxorubicinDoxorubicin may increase the hypocalcemic activities of Tiludronic acid.Approved, Investigational
DroxicamThe risk or severity of adverse effects can be increased when Droxicam is combined with Tiludronic acid.Withdrawn
DuvelisibThe risk or severity of adverse effects can be increased when Duvelisib is combined with Tiludronic acid.Investigational
E-6201The risk or severity of adverse effects can be increased when E-6201 is combined with Tiludronic acid.Investigational
EpirizoleThe risk or severity of adverse effects can be increased when Epirizole is combined with Tiludronic acid.Approved
EpirubicinEpirubicin may increase the hypocalcemic activities of Tiludronic acid.Approved
EsomeprazoleThe therapeutic efficacy of Tiludronic acid can be decreased when used in combination with Esomeprazole.Approved, Investigational
EtanerceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Tiludronic acid.Approved, Investigational
EthenzamideThe risk or severity of adverse effects can be increased when Ethenzamide is combined with Tiludronic acid.Experimental
EtodolacThe risk or severity of adverse effects can be increased when Etodolac is combined with Tiludronic acid.Approved, Investigational, Vet Approved
EtofenamateThe risk or severity of adverse effects can be increased when Etofenamate is combined with Tiludronic acid.Approved, Investigational
EtoricoxibThe risk or severity of adverse effects can be increased when Etoricoxib is combined with Tiludronic acid.Approved, Investigational
Evening primrose oilThe risk or severity of adverse effects can be increased when Evening primrose oil is combined with Tiludronic acid.Approved, Investigational
ExisulindThe risk or severity of adverse effects can be increased when Exisulind is combined with Tiludronic acid.Investigational
FelbinacThe risk or severity of adverse effects can be increased when Felbinac is combined with Tiludronic acid.Experimental
FenbufenThe risk or severity of adverse effects can be increased when Fenbufen is combined with Tiludronic acid.Approved
FenoprofenThe risk or severity of adverse effects can be increased when Fenoprofen is combined with Tiludronic acid.Approved
FentiazacThe risk or severity of adverse effects can be increased when Fentiazac is combined with Tiludronic acid.Experimental
FeprazoneThe risk or severity of adverse effects can be increased when Feprazone is combined with Tiludronic acid.Experimental
Ferulic acidThe risk or severity of adverse effects can be increased when Ferulic acid is combined with Tiludronic acid.Experimental
FloctafenineThe risk or severity of adverse effects can be increased when Floctafenine is combined with Tiludronic acid.Approved, Withdrawn
FlunixinThe risk or severity of adverse effects can be increased when Flunixin is combined with Tiludronic acid.Vet Approved
FlunoxaprofenThe risk or severity of adverse effects can be increased when Flunoxaprofen is combined with Tiludronic acid.Experimental
FlurbiprofenThe risk or severity of adverse effects can be increased when Flurbiprofen is combined with Tiludronic acid.Approved, Investigational
FramycetinFramycetin may increase the hypocalcemic activities of Tiludronic acid.Approved
GeneticinGeneticin may increase the hypocalcemic activities of Tiludronic acid.Experimental
GentamicinGentamicin may increase the hypocalcemic activities of Tiludronic acid.Approved, Vet Approved
GENTAMICIN C1AGENTAMICIN C1A may increase the hypocalcemic activities of Tiludronic acid.Experimental
GPX-150GPX-150 may increase the hypocalcemic activities of Tiludronic acid.Investigational
GuacetisalThe risk or severity of adverse effects can be increased when Guacetisal is combined with Tiludronic acid.Experimental
HigenamineThe risk or severity of adverse effects can be increased when Higenamine is combined with Tiludronic acid.Investigational
HydrotalciteThe serum concentration of Tiludronic acid can be decreased when it is combined with Hydrotalcite.Experimental, Investigational
Hygromycin BHygromycin B may increase the hypocalcemic activities of Tiludronic acid.Vet Approved
IbuprofenThe risk or severity of adverse effects can be increased when Ibuprofen is combined with Tiludronic acid.Approved
IbuproxamThe risk or severity of adverse effects can be increased when Ibuproxam is combined with Tiludronic acid.Withdrawn
IcatibantThe risk or severity of adverse effects can be increased when Icatibant is combined with Tiludronic acid.Approved
IdarubicinIdarubicin may increase the hypocalcemic activities of Tiludronic acid.Approved
Imidazole salicylateThe risk or severity of adverse effects can be increased when Imidazole salicylate is combined with Tiludronic acid.Experimental
IndobufenThe risk or severity of adverse effects can be increased when Indobufen is combined with Tiludronic acid.Investigational
IndomethacinThe serum concentration of Tiludronic acid can be increased when it is combined with Indomethacin.Approved, Investigational
IndoprofenThe risk or severity of adverse effects can be increased when Indoprofen is combined with Tiludronic acid.Withdrawn
IsepamicinIsepamicin may increase the hypocalcemic activities of Tiludronic acid.Experimental
IsoxicamThe risk or severity of adverse effects can be increased when Isoxicam is combined with Tiludronic acid.Withdrawn
KanamycinKanamycin may increase the hypocalcemic activities of Tiludronic acid.Approved, Investigational, Vet Approved
KebuzoneThe risk or severity of adverse effects can be increased when Kebuzone is combined with Tiludronic acid.Experimental
KetoprofenThe risk or severity of adverse effects can be increased when Ketoprofen is combined with Tiludronic acid.Approved, Vet Approved
KetorolacThe risk or severity of adverse effects can be increased when Ketorolac is combined with Tiludronic acid.Approved
LansoprazoleThe therapeutic efficacy of Tiludronic acid can be decreased when used in combination with Lansoprazole.Approved, Investigational
LeflunomideThe risk or severity of adverse effects can be increased when Leflunomide is combined with Tiludronic acid.Approved, Investigational
LisofyllineThe risk or severity of adverse effects can be increased when Lisofylline is combined with Tiludronic acid.Investigational
LonazolacThe risk or severity of adverse effects can be increased when Lonazolac is combined with Tiludronic acid.Experimental
LornoxicamThe risk or severity of adverse effects can be increased when Lornoxicam is combined with Tiludronic acid.Approved, Investigational
LoxoprofenThe risk or severity of adverse effects can be increased when Loxoprofen is combined with Tiludronic acid.Approved, Investigational
LumiracoxibThe risk or severity of adverse effects can be increased when Lumiracoxib is combined with Tiludronic acid.Approved, Investigational
Magnesium HydroxideThe serum concentration of Tiludronic acid can be decreased when it is combined with Magnesium Hydroxide.Approved
Magnesium oxideThe serum concentration of Tiludronic acid can be decreased when it is combined with Magnesium oxide.Approved
Magnesium peroxideThe serum concentration of Tiludronic acid can be decreased when it is combined with Magnesium peroxide.Experimental
Magnesium salicylateThe risk or severity of adverse effects can be increased when Magnesium salicylate is combined with Tiludronic acid.Approved
Magnesium silicateThe serum concentration of Tiludronic acid can be decreased when it is combined with Magnesium silicate.Approved, Experimental
Magnesium TrisilicateThe serum concentration of Tiludronic acid can be decreased when it is combined with Magnesium Trisilicate.Approved
MasoprocolThe risk or severity of adverse effects can be increased when Masoprocol is combined with Tiludronic acid.Approved, Investigational
Meclofenamic acidThe risk or severity of adverse effects can be increased when Meclofenamic acid is combined with Tiludronic acid.Approved, Vet Approved
Mefenamic acidThe risk or severity of adverse effects can be increased when Mefenamic acid is combined with Tiludronic acid.Approved
MeloxicamThe risk or severity of adverse effects can be increased when Meloxicam is combined with Tiludronic acid.Approved, Vet Approved
MesalazineThe risk or severity of adverse effects can be increased when Mesalazine is combined with Tiludronic acid.Approved
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Tiludronic acid.Investigational, Withdrawn
MetrizamideMetrizamide may increase the hypocalcemic activities of Tiludronic acid.Approved
MicronomicinMicronomicin may increase the hypocalcemic activities of Tiludronic acid.Experimental
MizoribineThe risk or severity of adverse effects can be increased when Mizoribine is combined with Tiludronic acid.Investigational
MofebutazoneThe risk or severity of adverse effects can be increased when Mofebutazone is combined with Tiludronic acid.Experimental
Mycophenolate mofetilThe risk or severity of adverse effects can be increased when Mycophenolate mofetil is combined with Tiludronic acid.Approved, Investigational
Mycophenolic acidThe risk or severity of adverse effects can be increased when Mycophenolic acid is combined with Tiludronic acid.Approved
NabumetoneThe risk or severity of adverse effects can be increased when Nabumetone is combined with Tiludronic acid.Approved
NafamostatThe risk or severity of adverse effects can be increased when Nafamostat is combined with Tiludronic acid.Approved, Investigational
NaftifineThe risk or severity of adverse effects can be increased when Naftifine is combined with Tiludronic acid.Approved
NaproxenThe risk or severity of adverse effects can be increased when Naproxen is combined with Tiludronic acid.Approved, Vet Approved
NeamineNeamine may increase the hypocalcemic activities of Tiludronic acid.Experimental
NeomycinNeomycin may increase the hypocalcemic activities of Tiludronic acid.Approved, Vet Approved
NepafenacThe risk or severity of adverse effects can be increased when Nepafenac is combined with Tiludronic acid.Approved
NetilmicinNetilmicin may increase the hypocalcemic activities of Tiludronic acid.Approved, Investigational
NifenazoneThe risk or severity of adverse effects can be increased when Nifenazone is combined with Tiludronic acid.Experimental
Niflumic AcidThe risk or severity of adverse effects can be increased when Niflumic Acid is combined with Tiludronic acid.Approved
NimesulideThe risk or severity of adverse effects can be increased when Nimesulide is combined with Tiludronic acid.Approved, Investigational, Withdrawn
NitroaspirinThe risk or severity of adverse effects can be increased when Nitroaspirin is combined with Tiludronic acid.Investigational
OlopatadineThe risk or severity of adverse effects can be increased when Olopatadine is combined with Tiludronic acid.Approved
OlsalazineThe risk or severity of adverse effects can be increased when Olsalazine is combined with Tiludronic acid.Approved
OmeprazoleThe therapeutic efficacy of Tiludronic acid can be decreased when used in combination with Omeprazole.Approved, Investigational, Vet Approved
OrgoteinThe risk or severity of adverse effects can be increased when Orgotein is combined with Tiludronic acid.Vet Approved
OxaprozinThe risk or severity of adverse effects can be increased when Oxaprozin is combined with Tiludronic acid.Approved
OxyphenbutazoneThe risk or severity of adverse effects can be increased when Oxyphenbutazone is combined with Tiludronic acid.Approved, Withdrawn
PantoprazoleThe therapeutic efficacy of Tiludronic acid can be decreased when used in combination with Pantoprazole.Approved
ParecoxibThe risk or severity of adverse effects can be increased when Parecoxib is combined with Tiludronic acid.Approved
ParomomycinParomomycin may increase the hypocalcemic activities of Tiludronic acid.Approved, Investigational
ParthenolideThe risk or severity of adverse effects can be increased when Parthenolide is combined with Tiludronic acid.Investigational
PhenylbutazoneThe risk or severity of adverse effects can be increased when Phenylbutazone is combined with Tiludronic acid.Approved, Vet Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Tiludronic acid.Approved, Investigational
PirarubicinPirarubicin may increase the hypocalcemic activities of Tiludronic acid.Investigational
PirfenidoneThe risk or severity of adverse effects can be increased when Pirfenidone is combined with Tiludronic acid.Approved, Investigational
PiroxicamThe risk or severity of adverse effects can be increased when Piroxicam is combined with Tiludronic acid.Approved, Investigational
PirprofenThe risk or severity of adverse effects can be increased when Pirprofen is combined with Tiludronic acid.Experimental
PlazomicinPlazomicin may increase the hypocalcemic activities of Tiludronic acid.Investigational
PlicamycinPlicamycin may increase the hypocalcemic activities of Tiludronic acid.Approved, Investigational, Withdrawn
PranoprofenThe risk or severity of adverse effects can be increased when Pranoprofen is combined with Tiludronic acid.Experimental, Investigational
ProglumetacinThe risk or severity of adverse effects can be increased when Proglumetacin is combined with Tiludronic acid.Experimental
PropacetamolThe risk or severity of adverse effects can be increased when Propacetamol is combined with Tiludronic acid.Approved, Investigational
PropyphenazoneThe risk or severity of adverse effects can be increased when Propyphenazone is combined with Tiludronic acid.Experimental
ProquazoneThe risk or severity of adverse effects can be increased when Proquazone is combined with Tiludronic acid.Experimental
PTC299The risk or severity of adverse effects can be increased when PTC299 is combined with Tiludronic acid.Investigational
PuromycinPuromycin may increase the hypocalcemic activities of Tiludronic acid.Experimental
RabeprazoleThe therapeutic efficacy of Tiludronic acid can be decreased when used in combination with Rabeprazole.Approved, Investigational
ResveratrolThe risk or severity of adverse effects can be increased when Resveratrol is combined with Tiludronic acid.Approved, Experimental, Investigational
RibostamycinRibostamycin may increase the hypocalcemic activities of Tiludronic acid.Approved, Investigational
RofecoxibThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Tiludronic acid.Investigational, Withdrawn
SabarubicinSabarubicin may increase the hypocalcemic activities of Tiludronic acid.Investigational
SalicylamideThe risk or severity of adverse effects can be increased when Salicylamide is combined with Tiludronic acid.Approved
Salicylic acidThe risk or severity of adverse effects can be increased when Salicylic acid is combined with Tiludronic acid.Approved, Vet Approved
SalsalateThe risk or severity of adverse effects can be increased when Salsalate is combined with Tiludronic acid.Approved
SemapimodThe risk or severity of adverse effects can be increased when Semapimod is combined with Tiludronic acid.Investigational
SeratrodastThe risk or severity of adverse effects can be increased when Seratrodast is combined with Tiludronic acid.Approved
SerrapeptaseThe risk or severity of adverse effects can be increased when Serrapeptase is combined with Tiludronic acid.Investigational
SisomicinSisomicin may increase the hypocalcemic activities of Tiludronic acid.Investigational
SP1049CSP1049C may increase the hypocalcemic activities of Tiludronic acid.Investigational
SpectinomycinSpectinomycin may increase the hypocalcemic activities of Tiludronic acid.Approved, Investigational, Vet Approved
SRT501The risk or severity of adverse effects can be increased when SRT501 is combined with Tiludronic acid.Investigational
StreptomycinStreptomycin may increase the hypocalcemic activities of Tiludronic acid.Approved, Vet Approved
StreptozocinStreptozocin may increase the hypocalcemic activities of Tiludronic acid.Approved
SulfasalazineThe risk or severity of adverse effects can be increased when Sulfasalazine is combined with Tiludronic acid.Approved
SulindacThe risk or severity of adverse effects can be increased when Sulindac is combined with Tiludronic acid.Approved
SuprofenThe risk or severity of adverse effects can be increased when Suprofen is combined with Tiludronic acid.Approved, Withdrawn
SuxibuzoneThe risk or severity of adverse effects can be increased when Suxibuzone is combined with Tiludronic acid.Experimental
TarenflurbilThe risk or severity of adverse effects can be increased when Tarenflurbil is combined with Tiludronic acid.Investigational
Technetium Tc-99m oxidronateTiludronic acid can cause a decrease in the absorption of Technetium Tc-99m oxidronate resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
TenidapThe risk or severity of adverse effects can be increased when Tenidap is combined with Tiludronic acid.Experimental
TenoxicamThe risk or severity of adverse effects can be increased when Tenoxicam is combined with Tiludronic acid.Approved
TepoxalinThe risk or severity of adverse effects can be increased when Tepoxalin is combined with Tiludronic acid.Vet Approved
TeriflunomideThe risk or severity of adverse effects can be increased when Teriflunomide is combined with Tiludronic acid.Approved
Tiaprofenic acidThe risk or severity of adverse effects can be increased when Tiaprofenic acid is combined with Tiludronic acid.Approved
TinoridineThe risk or severity of adverse effects can be increased when Tinoridine is combined with Tiludronic acid.Investigational
TobramycinTobramycin may increase the hypocalcemic activities of Tiludronic acid.Approved, Investigational
Tolfenamic AcidThe risk or severity of adverse effects can be increased when Tolfenamic Acid is combined with Tiludronic acid.Approved
TolmetinThe risk or severity of adverse effects can be increased when Tolmetin is combined with Tiludronic acid.Approved
TranilastThe risk or severity of adverse effects can be increased when Tranilast is combined with Tiludronic acid.Approved, Investigational
TribenosideThe risk or severity of adverse effects can be increased when Tribenoside is combined with Tiludronic acid.Experimental
TriptolideThe risk or severity of adverse effects can be increased when Triptolide is combined with Tiludronic acid.Investigational
TromethamineThe serum concentration of Tiludronic acid can be decreased when it is combined with Tromethamine.Approved
ValdecoxibThe risk or severity of adverse effects can be increased when Valdecoxib is combined with Tiludronic acid.Investigational, Withdrawn
ValrubicinValrubicin may increase the hypocalcemic activities of Tiludronic acid.Approved
ZaltoprofenThe risk or severity of adverse effects can be increased when Zaltoprofen is combined with Tiludronic acid.Approved, Investigational
ZileutonThe risk or severity of adverse effects can be increased when Zileuton is combined with Tiludronic acid.Approved, Investigational, Withdrawn
ZomepiracThe risk or severity of adverse effects can be increased when Zomepirac is combined with Tiludronic acid.Withdrawn
Zoptarelin doxorubicinZoptarelin doxorubicin may increase the hypocalcemic activities of Tiludronic acid.Investigational
ZorubicinZorubicin may increase the hypocalcemic activities of Tiludronic acid.Experimental
Food Interactions
  • Do not take aluminum or magnesium-containing antacids within 2 hours of taking tiludronate.
  • Take on an empty stomach (at least 2 hours before or after meals) with a full glass of plain water. Other beverages may reduce drug absorption.

References

Synthesis Reference

William Rocco, Sharon M. Laughlin, "Stable pharmaceutical compositions containing tiludronate hydrates and process for producing the pharmaceutical compositions." U.S. Patent US5656288, issued April, 1995.

US5656288
General References
  1. Murakami H, Takahashi N, Sasaki T, Udagawa N, Tanaka S, Nakamura I, Zhang D, Barbier A, Suda T: A possible mechanism of the specific action of bisphosphonates on osteoclasts: tiludronate preferentially affects polarized osteoclasts having ruffled borders. Bone. 1995 Aug;17(2):137-44. [PubMed:8554921]
  2. Rogers MJ: New insights into the molecular mechanisms of action of bisphosphonates. Curr Pharm Des. 2003;9(32):2643-58. [PubMed:14529538]
  3. Sansom LN, Necciari J, Thiercelin JF: Human pharmacokinetics of tiludronate. Bone. 1995 Nov;17(5 Suppl):479S-483S. [PubMed:8573422]
External Links
Human Metabolome Database
HMDB15265
KEGG Compound
C08141
PubChem Compound
60937
PubChem Substance
46505302
ChemSpider
54905
BindingDB
50442524
ChEBI
9598
ChEMBL
CHEMBL1350
PharmGKB
PA451688
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tiludronate
ATC Codes
M05BA05 — Tiludronic acid

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3TerminatedTreatmentOtospongiosis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
Not Available
Prices
Unit descriptionCostUnit
Skelid 200 mg tablet11.47USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US4876248No1993-01-302010-01-30Us
CA1327009No1994-02-152011-02-15Canada

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP-0.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility6.97 mg/mLALOGPS
logP0.62ALOGPS
logP1.32ChemAxon
logS-1.7ALOGPS
pKa (Strongest Acidic)1.03ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area115.06 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity65.11 m3·mol-1ChemAxon
Polarizability25.37 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8821
Blood Brain Barrier+0.92
Caco-2 permeable-0.69
P-glycoprotein substrateNon-substrate0.82
P-glycoprotein inhibitor INon-inhibitor0.9497
P-glycoprotein inhibitor IINon-inhibitor0.9907
Renal organic cation transporterNon-inhibitor0.9293
CYP450 2C9 substrateNon-substrate0.7291
CYP450 2D6 substrateNon-substrate0.8201
CYP450 3A4 substrateNon-substrate0.7084
CYP450 1A2 substrateNon-inhibitor0.7348
CYP450 2C9 inhibitorNon-inhibitor0.7404
CYP450 2D6 inhibitorNon-inhibitor0.8875
CYP450 2C19 inhibitorNon-inhibitor0.7287
CYP450 3A4 inhibitorNon-inhibitor0.8637
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.871
Ames testNon AMES toxic0.8148
CarcinogenicityCarcinogens 0.509
BiodegradationNot ready biodegradable0.9882
Rat acute toxicity2.9059 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.939
hERG inhibition (predictor II)Non-inhibitor0.9362
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
Thiophenol ethers / Chlorobenzenes / Alkylarylthioethers / Aryl chlorides / Organic phosphonic acids / Sulfenyl compounds / Organopnictogen compounds / Organophosphorus compounds / Organochlorides / Organic oxides
show 1 more
Substituents
Bisphosphonate / Aryl thioether / Thiophenol ether / Chlorobenzene / Halobenzene / Alkylarylthioether / Benzenoid / Aryl chloride / Monocyclic benzene moiety / Aryl halide
show 12 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
organochlorine compound (CHEBI:9598)

Targets

Kind
Small molecule
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
References
  1. Rogers MJ, Crockett JC, Coxon FP, Monkkonen J: Biochemical and molecular mechanisms of action of bisphosphonates. Bone. 2011 Jul;49(1):34-41. doi: 10.1016/j.bone.2010.11.008. Epub 2010 Nov 26. [PubMed:21111853]
Kind
Small molecule
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
References
  1. Jahnke W, Henry C: An in vitro assay to measure targeted drug delivery to bone mineral. ChemMedChem. 2010 May 3;5(5):770-6. doi: 10.1002/cmdc.201000016. [PubMed:20209564]
  2. Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, Mangood A, Russell RG, Ebetino FH: Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone. 2006 May;38(5):617-27. Epub 2005 Jul 20. [PubMed:16046206]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Proton-transporting atpase activity, rotational mechanism
Specific Function
Catalytic subunit of the peripheral V1 complex of vacuolar ATPase. V-ATPase vacuolar ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells.
Gene Name
ATP6V1A
Uniprot ID
P38606
Uniprot Name
V-type proton ATPase catalytic subunit A
Molecular Weight
68303.5 Da
References
  1. David P, Nguyen H, Barbier A, Baron R: The bisphosphonate tiludronate is a potent inhibitor of the osteoclast vacuolar H(+)-ATPase. J Bone Miner Res. 1996 Oct;11(10):1498-507. [PubMed:8889850]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EI...
Gene Name
PTPN1
Uniprot ID
P18031
Uniprot Name
Tyrosine-protein phosphatase non-receptor type 1
Molecular Weight
49966.44 Da
References
  1. Murakami H, Takahashi N, Tanaka S, Nakamura I, Udagawa N, Nakajo S, Nakaya K, Abe M, Yuda Y, Konno F, Barbier A, Suda T: Tiludronate inhibits protein tyrosine phosphatase activity in osteoclasts. Bone. 1997 May;20(5):399-404. [PubMed:9145236]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 17:14