Zoledronic acid

Bezeichnung:Zoledronic acid

CAS-Nr118072-93-8

Englisch Name:Zoledronic acid

CBNumberCB4395643

SummenformelC5H10N2O7P2

Molgewicht272.09

MOL-Datei118072-93-8.mol

Zoledronic acid physikalisch-chemischer Eigenschaften

Schmelzpunkt	193-2040C (dec)
Siedepunkt	764.0±70.0 °C(Predicted)
Dichte	2.13±0.1 g/cm3(Predicted)
storage temp.	Sealed in dry,Room Temperature
Löslichkeit	Soluble in Water (up to 2 mg/ml).
Aggregatzustand	solid
pka	1.41±0.10(Predicted)
Farbe	White or off-white
Stabilität	Stable for 2 years from date of purchase as supplied. Solutions in distilled water may be stored at -20° for up to 2 months.
CAS Datenbank	118072-93-8(CAS DataBase Reference)

Sicherheit

Kennzeichnung gefährlicher	Xi
R-Sätze:	21/22-36/37/38
S-Sätze:	24/25-36/37/39
HS Code	2933399090

Gefahreninformationscode (GHS)

Zoledronic acid Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R21/22:Gesundheitsschädlich bei Berührung mit der Haut und beim Verschlucken.
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
S-Sätze Betriebsanweisung:
S24/25:Berührung mit den Augen und der Haut vermeiden.
S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
Beschreibung
Zoledronic acid is a white, crystalline powder that is available in vials for reconstitution for IV infusion over at least 15 minutes. It does not undergo metabolic transformation and does not inhibit CYP450 enzymes. Clearance of this agent is dependent on the patient's creatinine clearance, not on dose. Serum creatinine levels should be evaluated before every treatment. Zolendronic acid is contraindicated in patients with severe renal impairment.
Chemische Eigenschaften
White Solid
Originator
Zometa,Novartis Pharma,Switz
Verwenden
bone resorption inhibitor
Verwenden
Bisphosphonate antiresorptive agent
Verwenden
Zoledronic acid induces apoptosis in osteoclasts by inhibiting enzymes of the mevalonate pathway and preventing the isoprenylation of small GTP-binding proteins such as Ras and Rho.
Definition
ChEBI: An imidazole compound having a 2,2-bis(phosphono)-2-hydroxyethane-1-yl substituent at the 1-position.
Manufacturing Process
With stirring and under reflux, 8.6 g (0.053 mole) of imidazol-4-yl acetic acid hydrochloride, 7.1 ml of 85% phosphoric acid and 25 ml of chlorobenzene are heated to 100°C. Then 13.9 ml of phosphorus trichloride are added dropwise at 100°C, whereupon evolution of gas occurs. Over the course of 30 min a dense mass precipitates from the reaction mixture. The batch is heated for 3 hours to 100°C and the supernatant chlorobenzene is removed by decantation. With stirring and under reflux, the residual viscous mass is heated to the boil for 3 hours with 40 ml of 9 N hydrochloric acid. The batch is filtered hot with the addition of carbon and the filtrate is diluted with acetone, whereupon the crude 2-(imidazol-4-yl)-1-hydroxy-ethane-1,1- diphosphonic acid precipitates. This product is recrystallised from water. Melting point: 238-240°C (dec.).
Trademarks
Zometa (Novartis).
Therapeutic Function
Bone calcium regulator
Biologische Funktion
Zoledronic acid, a bisphosphonate, was approved by the U.S. FDA in 2001 for the treatment of hypercalcemia of malignancy, a metabolic complication that can be life-threatening. Hypercalcemia of malignancy can occur in up to 50% of patients diagnosed with advanced breast cancer, multiple myeloma, and nonsmall cell lung cancer. This condition arises when chemical moieties produced by the tumor cause overstimulation of osteoclasts. When there is an increase in bone degradation, there is a concomitant release of calcium into the plasma. When serum concentrations of calcium rapidly elevate, the kidneys are unable to handle the overload, and hypercalcemia results. This can lead to dehydration, nausea, vomiting, fatigue, and confusion. Zoledronic acid effectively decreases plasma calcium concentrations via inhibition of bone resorption (inhibition of osteoclastic activity and induction of osteoclast apoptosis). It also prevents the increase in osteoclastic activity caused by tumor-based stimulatory factors. Additionally zoledronic acid has been approved by the U.S. FDA for the treatment of multiple myeloma and bone metastases associated with solid tumor–based cancers (e.g., prostrate and lung). This agent is currently in late-stage clinical trials for the treatment and prevention of osteoporosis and, if approved, will be formulated as a 5-mg, once-yearly IV infusion.
Clinical Use
Zoledronic acid is most commonly given to patients whose cancer is no longer responding to hormones, but it also may be given to prevent the bone thinning and weakening that results from hormonal treatments.
Arzneimittelwechselwirkung
Potentially hazardous interactions with other drugs
Other nephrotoxic drugs: use with caution as can enhance nephrotoxicity
Stoffwechsel
Zoledronic acid is not metabolised and is excreted unchanged via the kidney. Over the first 24 hours, 39 ± 16
% of the administered dose is recovered in the urine, while the remainder is principally bound to bone tissue.
Lager
Store at +4°C
Einzelnachweise
1) Green?et al. (1994),?Preclinical pharmacology of CGP 42446, a new, potent, heterocyclic bisphosphonate compound; J. Bone Miner. Res.,?9?745 2) Deeks and Perry (2008)?Zoledronic acid: a review of its use in the treatment of osteoporosis; Drugs Aging,?25?963 3) Perry and Figgitt (2004),?Zoledronic acid: a review of its use in patients with advanced cancer; Drugs,?64?1197 4) Koto?et al. (2010)?Zoledronic acid inhibits proliferation of human fibrosarcoma cells with induction of apoptosis and shows combined effects with other anticancer agents; Oncol. Rep.,?24?233 5) Tonyali?et al. (2010)?The role of zoledronic acid in the adjuvant treatment of breast cancer: current perspectives; Expert Opin. Pharmacother.,?11?2715

Zoledronic acid Upstream-Materialien And Downstream Produkte

Zoledronic acid Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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