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Details

Stereochemistry ACHIRAL
Molecular Formula C5H10N2O7P2.H2O
Molecular Weight 290.1049
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ZOLEDRONIC ACID

SMILES

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

InChI

InChIKey=FUXFIVRTGHOMSO-UHFFFAOYSA-N
InChI=1S/C5H10N2O7P2.H2O/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);1H2

HIDE SMILES / InChI

Description

Zoledronic acid (Reclast, Aclasta, Zometa) is an intravenous, highly potent amino-bisphosphonate approved worldwide, including in the USA, EU and Japan for use in patients with primary or secondary osteoporosis or low bone mass (approved indications vary between countries). Its high affinity to and long half-life in bone, and long duration of action allow for once-yearly administration, which has the potential to improve adherence to therapy. Zoledronic acid once yearly for up to 3 years improved bone mineral density (BMD) at several skeletal sites, reduced fracture risk and bone turnover, and/or preserved bone structure and mass relative to placebo in clinical studies in patients with primary or secondary osteoporosis. While additional benefits were seen when treatment was continued for up to 6 years, as evidenced by a reduced risk of vertebral fractures and higher BMD relative to 3 years’ therapy, there was the minimal advantage of treatment beyond 6 years. Therefore, in patients with low fracture risk, treatment discontinuation should be considered after approximately 5 years’ therapy. Zoledronic acid administered annually or once in 2 years was also effective in preventing bone loss in patients with low bone mass. Zoledronic acid was generally well tolerated, with the most common adverse events (AEs) being transient, mild-to-moderate post-infusion symptoms, which decreased with subsequent infusions.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
4.1 nM [IC50]
97.0 µM [IC50]
92.0 nM [IC50]
62.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Zometa
Primary
Zometa
Primary
Zometa
Primary
Zometa
Primary
Zometa

Cmax

ValueDoseCo-administeredAnalytePopulation
264 ng/mL
4 mg single, intravenous
ZOLEDRONIC ACID plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
420 ng × h/mL
4 mg single, intravenous
ZOLEDRONIC ACID plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
39 h
4 mg single, intravenous
ZOLEDRONIC ACID plasma
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as victim

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
The maximum recommended dose of Zometa in hypercalcemia of malignancy is 4 mg. The 4 mg dose must be given as a single-dose intravenous infusion over no less than 15 minutes.
Route of Administration: Intravenous
In Vitro Use Guide
For the transfection of the T24 human bladder cancer cells, pCMV6 empty vector (OriGene, Rockville, MD, USA) and pCMV6 TAp73 vector were transfected into cells using Lipofectamine™ 2000 (Invitrogen Life Technologies). After 6 h, the medium was refreshed and cultured for 48 h. Then the cells were treated with ZA (200 μM).