Drug/Small Molecule:
tiludronate

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PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all tiludronate variant annotations

Gene ? Variant?
(142)
Alternate Names ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA No Variant Annotations available
rs16944 -598T>C, 113594867A>G, 3343530A>G, 4490T>C, IL1B: -511 C/T
A > G
5' Flanking
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 142
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Acide tiludronique [INN-French]
  • Acido tiludronico [INN-Spanish]
  • Acidum tiludronicum [INN-Latin]
  • Tiludronate disodium
  • Tiludronic Acid Disodium Salt
  • Tiludronic acid
Trade Names
  • Skelid
Brand Mixture Names

PharmGKB Accession Id:
PA451688

Description

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

Source: Drug Bank

Indication

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

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

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.

Source: Drug Bank

Pharmacology

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.

Source: Drug Bank

Food Interaction

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.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

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

Source: Drug Bank

Protein Binding

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

Source: Drug Bank

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.

Source: Drug Bank

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.

Source: Drug Bank

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.

Source: Drug Bank

Clearance

Source: Drug Bank

Route of Elimination

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

Source: Drug Bank

Chemical Properties

Chemical Formula

C7H9ClO6P2S

Source: Drug Bank

Isomeric SMILES

C1=CC(=CC=C1SC(P(=O)(O)O)P(=O)(O)O)Cl

Source: Drug Bank

OP(O)(=O)C(SC1=CC=C(Cl)C=C1)P(O)(O)=O

Source: Drug Bank

Canonical SMILES

OP(O)(=O)C(SC1=CC=C(Cl)C=C1)P(O)(O)=O

Source: Drug Bank

Average Molecular Weight

318.608

Source: Drug Bank

Monoisotopic Molecular Weight

317.928359441

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
IL1B

Drug Targets

Gene Description
ATP6V1A (source: Drug Bank)
PTPN1 (source: Drug Bank)

Drug Interactions

Drug Description
Calcium The divalent cation of oral Calcium Chloride may significantly decrease the absorption of Tiludronate by forming a nonabsorbable chelate. Oral dosing should be separated by at least 2 hours. (source: Drug Bank)
Magnesium The divalent cation of oral Magnesium oxide may significantly decrease the absorption of Tiludronate by forming a nonabsorbable chelate. Oral dosing should be separated by at least 2 hours. (source: Drug Bank)

Curated Information ?

EvidenceDisease
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Osteitis Deformans

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to tiludronate: 1

No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
-511 C/T IL1B gene polymorphism is associated to resistance to bisphosphonates treatment in Paget disease of bone. Bone. 2006. Corral-Gudino Luis, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0024-1800-16
DrugBank:
DB01133
ChEBI:
15847
KEGG Compound:
C08141
PubChem Compound:
60937
PubChem Substance:
10341
46505302
ChemSpider:
54905
FDA Drug Label at DailyMed:
25369752-9d6c-4802-823c-c4205339a525

Clinical Trials

These are trials that mention tiludronate and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.