Chemical: Drug
zoledronate

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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.

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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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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 variant annotations for zoledronate

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No Clinical Annotations available VA
rs1152003 NC_000003.11:g.12477055G>C, NC_000003.12:g.12435556G>C, NG_011749.1:g.152707G>C, XM_011533842.1:c.1270+18402G>C, rs1625302, rs58390878, rs60048336
G > C
SNP
No VIP available No Clinical Annotations available VA
rs11730582 NC_000004.11:g.88896421T>C, NC_000004.12:g.87975269T>C, NG_030362.1:g.4620T>C, NM_000582.2:c.-546T>C, NM_001040058.1:c.-546T>C, NM_001040060.1:c.-546T>C, NM_001251829.1:c.-546T>C, NM_001251830.1:c.-696T>C
T > C
SNP
No VIP available No Clinical Annotations available VA
rs12458117 NC_000018.10:g.62360215G>A, NC_000018.9:g.60027448G>A, NG_008098.1:g.39901G>A, NM_001270949.1:c.616+166G>A, NM_001270950.1:c.616+166G>A, NM_001270951.1:c.616+166G>A, NM_001278268.1:c.574+166G>A, NM_003839.2:c.616+166G>A, NM_003839.3:c.616+166G>A, XM_005266777.1:c.616+166G>A, XM_011526244.1:c.631+166G>A, XM_011526245.1:c.508+166G>A, XR_935263.1:n.646+166G>A, rs56781861
G > A
SNP
No VIP available No Clinical Annotations available VA
rs1544410 NC_000012.11:g.48239835C>T, NC_000012.12:g.47846052C>T, NG_008731.1:g.63980G>A, NM_000376.2:c.1024+283G>A, NM_001017535.1:c.1024+283G>A, NM_001017536.1:c.1174+283G>A, XM_006719587.2:c.1024+283G>A, XM_011538720.1:c.1024+283G>A, XR_944903.1:n.-763C>T, rs386536760, rs56495123, rs56911380
C > T
SNP
No VIP available No Clinical Annotations available VA
rs1800012 NC_000017.10:g.48277749C=, NC_000017.10:g.48277749C>A, NC_000017.11:g.50200388C=, NC_000017.11:g.50200388C>A, NG_007400.1:g.6252G=, NG_007400.1:g.6252G>T, NM_000088.3:c.104-441G=, NM_000088.3:c.104-441G>T, XM_005257058.1:c.104-441G=, XM_005257058.1:c.104-441G>T, XM_005257058.3:c.104-441G=, XM_005257058.3:c.104-441G>T, XM_005257059.1:c.104-441G=, XM_005257059.1:c.104-441G>T, XM_005257059.3:c.104-441G=, XM_005257059.3:c.104-441G>T, XM_011524341.1:c.104-441G=, XM_011524341.1:c.104-441G>T, rs58312232, rs8179177
C > A
SNP
No VIP available CA No Variant Annotations available
rs1934951 NC_000010.10:g.96798548C>T, NC_000010.11:g.95038791C>T, NG_007972.1:g.35707G>A, NM_000770.3:c.1291+106G>A, NM_001198853.1:c.1081+106G>A, NM_001198854.1:c.985+106G>A, NM_001198855.1:c.1081+106G>A, XR_246073.1:n.1426+106G>A, XR_945610.1:n.1426+106G>A, rs60958510
C > T
SNP
No VIP available No Clinical Annotations available VA
rs2073618 NC_000008.10:g.119964052G>C, NC_000008.11:g.118951813G>C, NG_012202.1:g.5332C>G, NM_002546.3:c.9C>G, NP_002537.3:p.Asn3Lys, XM_005250756.1:c.-625G>C, XM_005250756.2:c.-625G>C, rs17751701, rs60810341
G > C
SNP
N3K
No VIP available CA VA
rs2297480 NC_000001.10:g.155279482T>G, NC_000001.11:g.155309691T>G, NG_045218.1:g.5944T>G, NM_001135821.1:c.-1-98T>G, NM_001135822.1:c.-1-373T>G, NM_001242824.1:c.-22-352T>G, NM_001242825.1:c.-175+726T>G, NM_002004.3:c.-1-98T>G, XM_005244962.1:c.-1-373T>G, XM_005244963.1:c.-22-352T>G, XM_005245266.1:c.-1000A>C, XM_005245266.3:c.-1000A>C, XM_011509639.1:c.-1000A>C, rs59477014
T > G
SNP
No VIP available No Clinical Annotations available VA
rs243865 NC_000016.10:g.55477894C>T, NC_000016.9:g.55511806C>T, NG_008989.1:g.3726C>T, NM_001302508.1:c.-1147C>T, NM_004530.5:c.-1586C>T, rs17859818, rs2071338, rs58165103
C > T
SNP
No VIP available No Clinical Annotations available VA
rs731236 NC_000012.11:g.48238757A>G, NC_000012.12:g.47844974A>G, NG_008731.1:g.65058T>C, NM_000376.2:c.1056T>C, NM_001017535.1:c.1056T>C, NM_001017536.1:c.1206T>C, NP_000367.1:p.Ile352=, NP_001017535.1:p.Ile352=, NP_001017536.1:p.Ile402=, XM_006719587.2:c.1056T>C, XM_011538720.1:c.1056T>C, XP_006719650.1:p.Ile352=, XP_011537022.1:p.Ile352=, XR_944903.1:n.-1841A>G, rs118037316, rs17777794, rs17880019, rs2228571, rs386609145, rs59730659
A > G
SNP
I352I
No VIP available No Clinical Annotations available VA
rs7975232 NC_000012.11:g.48238837C>A, NC_000012.12:g.47845054C>A, NG_008731.1:g.64978G>T, NM_000376.2:c.1025-49G>T, NM_001017535.1:c.1025-49G>T, NM_001017536.1:c.1175-49G>T, XM_006719587.2:c.1025-49G>T, XM_011538720.1:c.1025-49G>T, XR_944903.1:n.-1761C>A, rs17879735
C > A
SNP
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • ZOL
  • Zoledronic acid
Trade Names
  • Aclasta
  • Reclast
  • Reclast (Novartis)
  • Zometa
  • Zometa (Novartis)
  • Zometa Concentrate
Brand Mixture Names

PharmGKB Accession Id

PA10235

Type(s):

Drug

Description

Zoledronate (zoledronic acid, marketed by Novartis under the trade names Zometa and Reclast) is a bisphosphonate. Zometa is used to prevent skeletal fractures in patients with cancers such as multiple myeloma and prostate cancer. It can also be used to treat hypercalcemia of malignancy and can be helpful for treating pain from bone metastases.

An annual dose of Zoledronate may also prevent recurring fractures in patients with a previous hip fracture.

Zoledronate is a single 5 mg infusion for the treatment of Paget's disease of bone. In 2007, the FDA also approved Reclast for the treatment of postmenopausal osteoporosis.

Source: Drug Bank

Indication

For the treatment of hypercalcemia of malignancy. Also for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. In May of 2007, the drug was approved for treatment of Paget's Disease.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

The action of zoledronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Zoledronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates such as zoledronate appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.

Source: Drug Bank

Pharmacology

Zoledronate is a bisphosphonic acid which is an inhibitor of osteoclastic bone resorption. Zoledronate is used to prevent osteoporosis and skeletal fractures, particularly in patients with cancers such as multiple myeloma and prostate cancer. It can also be used to treat hypercalcemia, particularly hypercalcemia of malignancy. It can also be helpful for treating pain from bone metastases.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Zoledronate does not inhibit human P450 enzymes in vitro and does not undergo biotransformation in vivo.

Source: Drug Bank

Protein Binding

Approximately 22% bound in human plasma, independent of the concentration. However, Canadian product information states binding to human plasma protein is approximately 56%.

Source: Drug Bank

Absorption

Poorly absorbed (oral absorption is about 1% of what intravenous absorption is).

Source: Drug Bank

Half-Life

146 hours

Source: Drug Bank

Toxicity

There is no experience of acute overdose. Two patients received zoledronate (32 mg) over 5 minutes in clinical trials. Neither patient experienced any clinical or laboratory toxicity. Overdosage may cause clinically significant hypocalcemia, hypophosphatemia, and hypomagnesemia.

Source: Drug Bank

Clearance

  • Renal cl=3.7 +/- 2.0 L/h

Source: Drug Bank

Route of Elimination

In 64 patients with cancer and bone metastases, on average (± s.d.) 39 ± 16% of the administered zoledronic acid dose was recovered in the urine within 24 hours, with only trace amounts of drug found in urine post-Day 2.

Source: Drug Bank

Chemical Properties

Chemical Formula

C5H10N2O7P2

Source: Drug Bank

Isomeric SMILES

C1=CN(C=N1)CC(O)(P(=O)(O)O)P(=O)(O)O

Source: Drug Bank

OC(CN1C=CN=C1)(P(O)(O)=O)P(O)(O)=O

Source: Drug Bank

Canonical SMILES

OC(CN1C=CN=C1)(P(O)(O)=O)P(O)(O)=O

Source: Drug Bank

Average Molecular Weight

272.0896

Source: Drug Bank

Monoisotopic Molecular Weight

271.996323708

Source: Drug Bank

SMILES

OC(CN1C=CN=C1)(P(O)(O)=O)P(O)(O)=O

Source: Drug Bank

InChI String

InChI=1S/C5H10N2O7P2/c8-5(15(9,10)11,16(12,13)14)3-7-2-1-6-4-7/h1-2,4,8H,3H2,(H2,9,10,11)(H2,12,13,14)

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 ?

Drug Targets

Gene Description
FDPS (source: Drug Bank )
GGPS1 (source: Drug Bank )
No related drugs are available.

Curated Information ?

Publications related to zoledronate: 10

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
A peroxisome proliferator-activated receptor gamma (PPARG) polymorphism is associated with zoledronic acid-related osteonecrosis of the jaw in multiple myeloma patients: analysis by DMET microarray profiling. British journal of haematology. 2011. Di Martino Maria T, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Genetic polymorphisms and other risk factors associated with bisphosphonate induced osteonecrosis of the jaw. International journal of oral and maxillofacial surgery. 2011. Katz J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Bisphosphonates pathway. Pharmacogenetics and genomics. 2011. Gong Li, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacogenetics of bisphosphonate-associated osteonecrosis of the jaw. Frontiers in bioscience (Elite edition). 2011. Marini Francesca, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Expectations, validity, and reality in pharmacogenetics. Journal of clinical epidemiology. 2010. Limdi Nita A, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A SNP in CYP2C8 is not associated with the development of bisphosphonate-related osteonecrosis of the jaw in men with castrate-resistant prostate cancer. Therapeutics and clinical risk management. 2010. English Bevin C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA 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
Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma: a genome-wide single nucleotide polymorphism analysis. Blood. 2008. Sarasquete Maria E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Modulatory effect of farnesyl pyrophosphate synthase (FDPS) rs2297480 polymorphism on the response to long-term amino-bisphosphonate treatment in postmenopausal osteoporosis. Current medical research and opinion. 2008. Marini Francesca, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging. Nature medicine. 2008. Varela Ignacio, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0078-0387-25
DrugBank:
DB00399
PDB:
ZOL
KEGG Drug:
D01968
PubChem Compound:
68740
PubChem Substance:
46507310
536160
Drugs Product Database (DPD):
2242725
BindingDB:
12578
ChemSpider:
61986
HET:
ZOL
Therapeutic Targets Database:
DAP001539
FDA Drug Label at DailyMed:
f0cdfa57-95e5-416b-bc2f-cde2491c2fd0

Clinical Trials

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

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

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Sources for PharmGKB drug information: DrugBank, PubChem.