Drug/Small Molecule:
clodronate

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PharmGKB has no annotated drug labels with pharmacogenomic information for this drug/small molecule. If you know of a drug label with PGx, send us a message.

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 clodronate variant annotations

Gene ? Variant?
(142)
Alternate Names ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA
rs1544410 1024+283G>A, 10383141C>T, 1174+283G>A, 48239835C>T, 63980G>A, VDR: BsmI, VDR:BsmI
C > T
Intronic
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
No VIP available CA VA
rs731236 10382063A>G, 1056T>C, 1206T>C, 48238757A>G, 65058T>C, Ile352=, Ile402=, NM_000376.2:c.1056T>C, NP_001017535.1:p.Ile352Ile, NP_001017536.1:p.Ile402Ile, VDR: TaqI, VDR:Taq1 T>t
A > G
Synonymous
Ile402Ile
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 142
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • clodronate
Trade Names
  • Acide Clodronique [INN-French]
  • Acido Clodronico [INN-Spanish]
  • Acidum Clodronicum [INN-Latin]
  • Bonefos
  • Clasteon
  • Dichloromethanediphosphonic acid
  • Dichloromethylidene diphosphonate
  • Loron
  • Ostac
Brand Mixture Names

PharmGKB Accession Id:
PA10239

Description

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

Source: Drug Bank

Indication

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

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. 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 beta-gamma-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.

Source: Drug Bank

Pharmacology

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.

Source: Drug Bank

Food Interaction

Food decreases absorption. Take on an empty stomach.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Clodronate is not metabolized in humans.

Source: Drug Bank

Protein Binding

2%-36%

Source: Drug Bank

Absorption

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

Source: Drug Bank

Half-Life

Approximately 13 hours.

Source: Drug Bank

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.

Source: Drug Bank

Chemical Properties

Chemical Formula

CH4Cl2O6P2

Source: Drug Bank

Isomeric SMILES

C(P(=O)(O)O)(P(=O)(O)O)(Cl)Cl

Source: Drug Bank

OP(O)(=O)C(Cl)(Cl)P(O)(O)=O

Source: Drug Bank

Canonical SMILES

OP(O)(=O)C(Cl)(Cl)P(O)(O)=O

Source: Drug Bank

Average Molecular Weight

244.892

Source: Drug Bank

Monoisotopic Molecular Weight

243.886016298

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
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
VDR

Drug Targets

Gene Description
PTPN1 (source: Drug Bank)
SLC25A4 (source: Drug Bank)
SLC25A5 (source: Drug Bank)
SLC25A6 (source: Drug Bank)

Drug Interactions

Drug Description
clodronate Formation of non-absorbable complexes (source: Drug Bank)
clodronate Formation of non-absorbable complexes (source: Drug Bank)
aluminium Formation of non-absorbable complexes (source: Drug Bank)
Calcium Formation of non-absorbable complexes (source: Drug Bank)
Calcium Formation of non-absorbable complexes (source: Drug Bank)
dihydroxyaluminium Formation of non-absorbable complexes (source: Drug Bank)
estramustine Increases the levels of estramustine (source: Drug Bank)
estramustine Increases the levels of estramustine (source: Drug Bank)
iron Formation of non-absorbable complexes (source: Drug Bank)
iron Formation of non-absorbable complexes (source: Drug Bank)
Magnesium Formation of non-absorbable complexes (source: Drug Bank)
Magnesium Formation of non-absorbable complexes (source: Drug Bank)
magnesium oxide Formation of non-absorbable complexes (source: Drug Bank)
sucralfate Formation of non-absorbable complexes (source: Drug Bank)
sucralfate Formation of non-absorbable complexes (source: Drug Bank)
clodronate Clodronate increases the levels of estramustine (source: Drug Bank)
clodronate Clodronate increases the levels of estramustine (source: Drug Bank)
clodronate Formation of non-absorbable complexes (source: Drug Bank)
clodronate Formation of non-absorbable complexes (source: Drug Bank)
clodronate Formation of non-absorbable complexes (source: Drug Bank)

Curated Information ?

Publications related to clodronate: 7

No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Vitamin D receptor gene polymorphisms predict acquired resistance to clodronate treatment in patients with Paget's disease of bone. Calcified tissue international. 2008. Mossetti Giuseppe, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Vitamin D receptor genotypes and response to zoledronic acid therapy in thalassemia-induced osteoporosis. Annals of hematology. 2008. Otrock Zaher K, et al. PubMed
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
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
BsmI vitamin D receptor genotypes influence the efficacy of antiresorptive treatments in postmenopausal osteoporotic women. A 1-year multicenter, randomized and controlled trial. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2005. Palomba Stefano, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Effectiveness of alendronate treatment in postmenopausal women with osteoporosis: relationship with BsmI vitamin D receptor genotypes. Clinical endocrinology. 2003. Palomba Stefano, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Two polymorphisms in the vitamin D receptor gene--association with bone mass and 5-year change in bone mass with or without hormone-replacement therapy in postmenopausal women: the Danish Osteoporosis Prevention Study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2002. Tofteng C L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
VDR genotype and response to etidronate therapy in late postmenopausal women. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 1999. Marc J, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00720
ChEBI:
110423
PubChem Compound:
25419
PubChem Substance:
168153
46508646
Drugs Product Database (DPD):
1984837
BindingDB:
50216172
ChemSpider:
23731
Therapeutic Targets Database:
DAP000564

Clinical Trials

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

Common Searches

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