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Gallium nitrate
Gallium nitrate
Gallium nitrate
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Gallium nitrate
Names
IUPAC name
Gallium trinitrate
Other names
Gallium(III) nitrate
Nitric acid, gallium salt
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.033.453 Edit this at Wikidata
EC Number
  • 236-815-5
UNII
UN number 1477
  • InChI=1S/Ga.3NO3/c;3*2-1(3)4/q+3;3*-1
    Key: CHPZKNULDCNCBW-UHFFFAOYSA-N
  • [N+](=O)([O-])[O-].[N+](=O)([O-])[O-].[N+](=O)([O-])[O-].[Ga+3]
Properties
Ga(NO3)3
Molar mass 255.7377 g/mol
Hazards
GHS labelling:
GHS03: OxidizingGHS05: CorrosiveGHS07: Exclamation mark
Danger
H272, H314, H315, H319, H335
P210, P220, P221, P260, P261, P264, P271, P280, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P310, P312, P321, P332+P313, P337+P313, P362, P363, P370+P378, P403+P233, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Gallium nitrate (brand name Ganite) is the gallium salt of nitric acid with the chemical formula Ga(NO3)3. It is a drug used to treat symptomatic hypercalcemia secondary to cancer. It works by preventing the breakdown of bone through the inhibition of osteoclast activity, thus lowering the amount of free calcium in the blood.[1][2] Gallium nitrate is also used to synthesize other gallium compounds.

History

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Gallium (Ga) was discovered in 1875 by P.É. Lecoq de Boisbaudran.[3] In most of its compounds, gallium is found with an oxidation number of 3+. Gallium chemically behaves similarly to iron 3+ when forming a coordination complex.[4] That means gallium(III) and iron(III) are similar in similar coordination number, electrical charge, ion diameter and electron configuration.

Biological activity

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Gallium atoms are bound to the phosphates of DNA at low gallium concentrations, forming a stable complex.[5] Gallium competes with magnesium in DNA binding, since its DNA affinity is 100 times higher than that of magnesium. No interactions have been found between the metal and DNA bases.[6] According to Hedley et al., gallium inhibits replicative DNA synthesis, the major gallium-specific target probably being ribonucleotide reductase.[6] In addition to that, it was reported by Chitambar that gallium binds to transferrin more strongly than iron. The transferrin gallium complex inhibits DNA synthesis by acting on the M2 subunit of ribonucleotide reductase.[7] Gallium(III) seems to act as an antagonist to the actions of several ions (Ca2+, Mg2+, Fe2+ and Zn2+) in processes of cellular metabolism. The action of gallium on bone metabolism decreases hypercalcemia associated with cancer. However, gallium is mostly found within the cell as a salt in lysosomes.

Preparation

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Gallium nitrate is commercially available as the hydrate. The nonahydrate may also be prepared by dissolving gallium in nitric acid, followed by recrystallization.[8] The structure of gallium nitrate nonahydrate has been determined by X-ray crystallography.[9]

Use and manufacturing

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Preparation of gallium nitride from gallium nitrate

[edit]

GaN powder was synthesized using a direct current (DC) non-transferred arc plasma.[10]

Medication Information

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Gallium nitrate injection (Ganite) is a clear, colorless, odorless, solution of the nonahydrate (Ga(NO3)3·9H2O) which is readily soluble in water. Each mL of Ganite contains 25 mg of Ga(NO3)3 (anhydrous basis) and sodium citrate dihydrate 28.75 mg. The solution may contain sodium hydroxide or hydrochloric acid for pH adjustment to 6.0-7.0.[11]

Overdose

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Use of higher doses of gallium nitrate than recommended may cause nausea, vomiting and increases risk of chronic kidney disease. In the case of overdose, serum calcium should be monitored, patients should receive vigorous hydration for 2–3 days and any further drug administrations should be discontinued.[11]

Treatment

[edit]

The action of gallium in gallium nitrate on bone metabolism decreases the hypercalcemia associated with cancer. Gallium inhibits osteoclastic activity and therefore decreases hydroxyapatite crystal formation[citation needed], with adsorption of gallium onto the surfaces of hydroxyapatite crystals.[12] Also, the increased concentration of gallium in the bone leads to increasing the synthesis of collagen as well as the formation of the bone tissue inside the cell. It has been reported that a protracted infusion was effective against cancer-associated hypercalcemia.[13] Preliminary studies in bladder carcinoma, carcinoma of the urothelium and lymphomas are also promising.[14] Another interesting schedule of subcutaneous injection with low doses of gallium nitrate has been proposed, especially for the treatment of bone metastases, but the definitive results have not yet been published.[15]

Chemical reactivity

[edit]

Gallium nitrate can react with reducing agents to generate heat and products that may be gaseous. The products[which?] may themselves be capable of further reactions (such as combustion in the air). The chemical reduction of materials in this group[which?] can be rapid, but do not necessarily proceed without addition of heat, catalyst or addition of a solvent. Explosive mixtures of gallium nitrate with reducing agents often remain unchanged for long periods if the reaction is not initiated. It is soluble in water; dissolution weakens but does not nullify its oxidizing capability. Generally, inorganic oxidizing agents can react violently with active metals, cyanides, esters, and thiocyanates.[11]

Adverse reactions

[edit]

Kidney

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Adverse renal effects have been reported in about 12.5% of patients treated with gallium nitrate. Two patients receiving gallium nitrate and one patient receiving calcitonin developed acute renal failure in a controlled trial of patients with cancer-related hypercalcemia. Also, it was reported that gallium nitrate should not be administered to patients with serum creatinine >2.5 mg/dL.[11]

Blood pressure

[edit]

In a controlled trial of patients, it was noticed a decrease in mean systolic and diastolic blood pressure after the treatment with gallium nitrate. The decrease in blood pressure was asymptomatic and did not require specific treatment.[11]

Hematologic

[edit]

High doses of gallium nitrate were associated with anemia when used in treating patients for advanced cancer. As a result, several patients have received red blood cell transfusions.[11]

See also

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References

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Revisions and contributorsEdit on WikipediaRead on Wikipedia

Gallium nitrate

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Gallium nitrate is an with the Ga(NO₃)₃, typically encountered as a white crystalline powder or form, highly soluble in and exhibiting a around 110°C where it decomposes. It serves primarily as a pharmaceutical agent, administered intravenously to treat hypercalcemia of by inhibiting osteoclast-mediated , thereby reducing elevated serum calcium levels in cancer patients. As a trivalent salt of , a heavy metal with chemical similarities to iron, gallium nitrate binds to and accumulates in bone tissue, where it suppresses bone turnover and exhibits anti-inflammatory effects by inhibiting cytokines like IL-1β and matrix metalloproteinases. Its antineoplastic properties have been demonstrated in clinical trials, showing response rates of up to 30% in relapsed non-Hodgkin's and activity against urothelial cancers, though it is no longer commercially available following the discontinuation of the brand Ganite in 2012. Beyond , gallium nitrate has been investigated for treating bone disorders such as Paget's disease, , and due to its ability to modulate calcium and reduce pathological , with renal excretion as its primary elimination route and as a key dose-limiting side effect. It has also been investigated in clinical trials for patients with chronic infections, such as those caused by or nontuberculous mycobacteria. In non-medical applications, it acts as a precursor for synthesizing gallium-based materials like gallium oxide, leveraging its and reactivity in aqueous solutions.

Physical and Chemical Properties

Molecular Structure

Gallium nitrate has the Ga(NO₃)₃, consisting of a gallium(III) cation and three anions. It is most commonly isolated and used in the form of its nonahydrate, Ga(NO₃)₃·9H₂O, which incorporates nine molecules of of hydration. The Ga³⁺ possesses a high charge-to-radius ratio, with an of 62 pm for six-coordinate geometry, rendering it a hard Lewis acid that preferentially binds to hard donor atoms such as oxygen. This property drives the formation of coordination complexes where Ga³⁺ achieves an octahedral geometry through bonding to oxygen-containing ligands, including those from groups or molecules. Due to its similar charge and to Fe³⁺ (64 pm), Ga³⁺ exhibits analogous coordination behavior, forming stable octahedral complexes with oxygen donors like , which can act as monodentate or bidentate ligands depending on the environment. X-ray crystallography of related hydrate forms, such as the trihydrate Ga(H₂O)₆₃·3H₂O, confirms octahedral coordination around Ga³⁺ by six water oxygen atoms, with nitrate ions serving as counteranions linked via hydrogen bonding; similar structural motifs are expected in the nonahydrate, emphasizing the Lewis acidity-driven coordination.

Physical Characteristics

Gallium nitrate is most commonly utilized in its hydrated form, particularly the nonahydrate Ga(NO₃)₃·9H₂O, which presents as a white, slightly hygroscopic crystalline powder. This form is odorless and maintains structural integrity as a solid under ambient conditions. The nonahydrate exhibits a of approximately 110 °C, though it undergoes rather than a true phase change at this temperature. The form decomposes prior to , preventing observation of a distinct behavior. It lacks a defined , instead decomposing at elevated temperatures without entering a phase. Under standard conditions of and , gallium nitrate remains stable, showing no significant degradation when stored properly away from incompatible materials. Its hygroscopic character requires handling in controlled humidity environments to prevent moisture absorption and potential clumping.

History

Discovery of

was discovered in 1875 by the French chemist through spectroscopic examination of a zinc blende (sphalerite) ore sample from the . While analyzing the ore for rare earth elements, Lecoq de Boisbaudran observed two new violet spectral lines at 417.2 nm and 403.1 nm, which he attributed to an undiscovered element that matched Dmitri Mendeleev's prediction for "eka-aluminum," an element below aluminum in the periodic table. This spectroscopic detection was a landmark in elemental discovery, confirming Mendeleev's periodic law and highlighting the power of emission for identifying trace elements in complex minerals. Following the spectroscopic identification, Lecoq de Boisbaudran named the new element gallium after "Gallia," the Latin term for , honoring his homeland; some accounts also note a possible secondary reference to his surname, as "le coq" (rooster) translates to "gallus" in Latin. To isolate the element, he processed approximately 430 kilograms of blende ore, yielding only about 0.65 grams of impure gallium initially. Early isolation involved dissolving the ore in acids, precipitating gallium as , redissolving in to form gallium (GaCl₃), and further purifying via fractional precipitation and to obtain the metallic form by late 1875. These initial efforts produced milligram quantities of gallium mixed with , marking the first chemical characterization of the element as a soft, silvery metal with properties akin to aluminum. The preparation of gallium nitrate (Ga(NO₃)₃) soon followed the isolation of metallic , achieved in the late 19th century by dissolving the metal in dilute , a standard method for forming metal from reactive elements. This reaction proceeds as gallium oxidizes in the acid, yielding the soluble nitrate salt, which could then be concentrated by evaporation and crystallized as the . Early studies of gallium nitrate focused on its and stability, confirming gallium's +3 and its chemical analogies to aluminum and iron. In its early years, and its nitrate compound saw limited applications, primarily confined to fundamental chemical research on elements and spectroscopic , as the metal's scarcity—derived from trace impurities in ores—restricted broader exploration until the . Notably, the Ga³⁺ ion's (62 pm) closely resembles that of Fe³⁺ (64.5 pm), a similarity that would later inform biological investigations but initially served only to highlight gallium's reactivity in aqueous solutions.

Development as a Therapeutic Agent

Interest in gallium compounds for therapeutic purposes emerged in the 1930s, when early studies demonstrated the antimicrobial potential of gallium tartrate against syphilis in rabbits and trypanosomes in mice. By the late 1940s and into the 1950s, toxicologic investigations revealed that gallium tended to accumulate in inflamed tissues and tumors, prompting its exploration as a diagnostic agent in nuclear medicine using radioactive isotopes. The development of stable gallium nitrate as a therapeutic agent accelerated in the , following preclinical studies that identified its antitumor activity in animal models, including inhibition of tumor growth in rats and mice. Initial clinical trials in the late 1970s and early evaluated its and toxicity in patients with advanced cancers, confirming dose-dependent renal effects but also hinting at potential efficacy against lymphomas. These findings shifted focus toward its effects on bone , with key publications demonstrating that gallium nitrate inhibits osteoclast-mediated and collagen synthesis , while increasing bone calcium content . This research culminated in the U.S. Food and Drug Administration's approval of gallium nitrate (under the trade name Ganite) on January 17, 1991, for the treatment of cancer-related hypercalcemia refractory to hydration, marking its transition from experimental antineoplastic to established therapy for metabolic complications of malignancy. Post-2000 investigations expanded its evaluation for direct antitumor applications, including phase II trials showing activity in relapsed non-Hodgkin's lymphoma and bladder cancer, though adoption remained limited due to concerns over nephrotoxicity and the need for supportive hydration.

Synthesis and Preparation

Laboratory Synthesis

The primary method for laboratory synthesis of gallium nitrate involves the dissolution of high-purity metallic gallium in concentrated nitric acid at elevated temperatures, typically 50–80°C, to facilitate the reaction. The balanced reaction equation under these conditions is: Ga+6HNO3→Ga(NO3)3+3NO2+3H2O\text{Ga} + 6\text{HNO}_3 \to \text{Ga(NO}_3)_3 + 3\text{NO}_2 + 3\text{H}_2\text{O} This produces nitrogen dioxide gas and proceeds exothermically, requiring careful ventilation due to the toxic byproduct. Following the reaction, the solution is filtered to remove any undissolved residues and evaporated at 80–100°C until the nitric acid odor dissipates, concentrating the gallium nitrate. The concentrate is then cooled to 0–20°C, often with seeding using small amounts of pre-formed crystals (0.01–0.1 wt% ratio), to promote crystallization over 15–30 minutes. Purification is accomplished by recrystallization from deionized water, yielding colorless crystals of the nonahydrate form, Ga(NO3)3⋅9H2O\text{Ga(NO}_3)_3 \cdot 9\text{H}_2\text{O}, with purities exceeding 99.99% achievable via this bench-scale process. Laboratory yields are generally high, though gallium's amphoteric nature necessitates controlled acidic conditions to prevent formation of gallates from any trace basic contaminants or oxide layers on the metal surface.

Commercial Production

Commercial production of gallium nitrate begins with high-purity elemental , typically 99.9999% (6N) grade, sourced primarily as a byproduct from the processing of during aluminum extraction via the or from zinc ore refining. This is reacted with high-purity in large-scale reactors under controlled conditions, such as temperatures of 50–80°C, to form gallium nitrate solution through acid digestion. The resulting solution undergoes filtration to remove undissolved impurities, followed by concentration via at 80–100°C and cooling to 0–20°C to promote of gallium nitrate nonahydrate [Ga(NO₃)₃·9H₂O], which is then separated, washed, and dried at low temperatures (30–40°C) to yield a white, hygroscopic powder. For pharmaceutical applications, the process adheres to Good Manufacturing Practice (GMP) standards to ensure scalability and quality control. The crystallized gallium nitrate is redissolved in water, refiltered for sterility, and adjusted to a pH of 6.0–7.0 using sodium hydroxide or hydrochloric acid. Sodium citrate dihydrate (28.75 mg per mL) is incorporated as a stabilizer to prevent precipitation, and the solution is diluted to a concentration of 25 mg/mL gallium nitrate (anhydrous basis) with Sterile Water for Injection, USP. The final formulation, exemplified by the product Ganite, is sterilized by filtration, filled into single-use 20 mL vials containing 500 mg of gallium nitrate, and packaged in cartons for intravenous administration. Purity of the commercial gallium nitrate nonahydrate exceeds 99%, with trace metal impurities minimized to meet pharmaceutical specifications, as verified by techniques such as (ICP-MS). These processes enable efficient, large-volume production while maintaining the compound's stability and efficacy for medical formulations under GMP compliance.

Chemical Reactivity

Oxidation and Reduction Reactions

Gallium nitrate acts as an primarily due to the (NO₃⁻) group, which can oxidize metals or other reducing agents while being reduced to gaseous products such as (NO₂) or (NO). This reactivity arises from the strong oxidizing nature of the ion in acidic or neutral conditions, facilitating processes where the accepts electrons to form lower nitrogen species. The gallium(III) ion (Ga³⁺) in gallium nitrate can undergo reduction to metallic gallium (Ga⁰) or, less commonly, gallium(I) species, though the latter are highly unstable and tend to disproportionate. The standard for Ga³⁺ + 3e⁻ → Ga(s) is -0.549 V, indicating that reduction to the elemental form is thermodynamically feasible under appropriate conditions, such as with strong reducing agents like magnesium or aluminum, often following to gallium as an intermediate step. For instance, reactions with potent reducers like generate significant heat and evolve gases, including , as the nitrate is reduced and Ga³⁺ is partially lowered in . Thermal decomposition of gallium nitrate hydrate, Ga(NO₃)₃·xH₂O (where x ≈ 8–9), begins above 100°C, involving stepwise dehydration and nitrate breakdown that releases nitrogen oxides (NOx) and ultimately yields gallium(III) oxide (Ga₂O₃) as the stable product. At heating rates typical of thermogravimetric analysis, the process proceeds through intermediates like Ga(OH)₂NO₃ and GaO(OH), with NOx evolution confirming the redox nature of nitrate decomposition, while differential scanning calorimetry reveals endothermic dehydration followed by exothermic oxide formation. Gallium nitrate exhibits violent reactions with cyanides, thiocyanates, and strong reducing agents due to rapid interactions that can lead to explosions from heat and gas buildup. For example, contact with barium thiocyanate or triggers explosive , emphasizing the need for careful handling to mitigate risks from the oxidizing moiety.

Compatibility and Hazards

Gallium nitrate should be stored in a cool, dry, well-ventilated area away from combustible materials, reducing agents, and sources of ignition to prevent hazards and . It is incompatible with metals due to its corrosive nature and should be kept in or containers to avoid container degradation. As an oxidizer, gallium nitrate may intensify fires and is corrosive to metals, posing risks during handling. Aqueous solutions have a low of approximately 2, causing severe and eye irritation or burns upon contact. of dust or fumes, particularly nitrogen oxides (NOx) generated during or certain oxidation/reduction reactions, can irritate the . Safe handling requires the use of (PPE), including chemical-resistant gloves, safety goggles, and protective clothing to prevent skin and eye exposure. Operations should be conducted in a well-ventilated area or under a to minimize inhalation risks. In case of spills, evacuate the area, contain the material with absorbent pads, and neutralize with a base such as before cleanup to avoid further or reaction. Due to its nitrate content, improper disposal of gallium nitrate can contribute to nitrate pollution in water bodies, potentially leading to eutrophication. It must be treated as hazardous waste and disposed of according to local, state, and federal regulations, such as those outlined by the EPA for corrosive and oxidizing materials.

Industrial Applications

Synthesis of Gallium Nitride

Gallium nitrate serves as a key precursor in the synthesis of (GaN), a material essential for advanced . One prominent method involves a (DC) non-transferred arc plasma reaction, developed in 2016, which utilizes gallium nitrate hydrate (Ga(NO₃)₃·xH₂O) mixed with (C₃H₆N₆) or (NH₃) as nitrogen sources under high-temperature conditions. In this process, the reaction proceeds by vaporizing the gallium nitrate precursor in a plasma arc at approximately 8.4 kW power (300 A current and 28 V voltage) with as the carrier gas, followed by nitridation and subsequent annealing at 850°C for 3 hours in a to enhance crystallinity and purity. The overall reaction can be represented as Ga(NO₃)₃ reacting with the carbon/nitrogen source to form GaN nanopowder, releasing (NOₓ) byproducts, and yielding high-purity particles with a mean size of about 30 nm (ranging 10–60 nm) and gallium content up to 71.6 wt% after annealing. This plasma-based approach offers significant advantages over traditional organometallic methods like metalorganic vapor phase epitaxy (MOVPE) or metalorganic chemical vapor deposition (MOCVD), including lower costs due to the use of inexpensive inorganic precursors, faster synthesis times, and avoidance of lattice mismatch issues in epitaxial growth. The resulting GaN powder finds applications in light-emitting diodes (LEDs) for blue fluorescence and for high-efficiency devices. Recent advances include the integration of such innovative GaN synthesis techniques into Singapore's National Semiconductor Translation and Innovation Centre (NSTIC) for GaN, launched in June 2025, which supports advanced and positions the region as a hub for innovation as of November 2025.

Other Manufacturing Uses

Gallium nitrate serves as a key precursor in the synthesis of () polymorphs, including α-, β-, and γ-phases, through controlled precipitation methods. In this process, aqueous solutions of gallium nitrate are mixed with to form gallium hydroxide intermediates, which are then calcined at varying temperatures to yield the desired forms. This scalable approach is particularly useful for producing materials employed in optoelectronic and high-temperature applications. Due to its ability to generate Lewis acidic sites, gallium nitrate is incorporated into the preparation of heterogeneous catalysts, such as Ga-MCM-41 mesoporous silicas, for organic transformations. These catalysts facilitate reactions like liquid-phase by activating substrates through coordination with gallium's electron-deficient centers, offering advantages in selectivity and recyclability over homogeneous alternatives. The broader market for gallium compounds, encompassing nitrates used in electronic material precursors, is experiencing robust expansion driven by demand in semiconductors and related technologies. Projections indicate a (CAGR) of 25.4% from 2024 to 2025, reflecting increased adoption in high-performance devices. Emerging applications include the integration of gallium nitrate into nanocarriers for diagnostic purposes, such as gallium-based nanoplatforms that enhance and biosensing capabilities in cancer detection. These systems leverage the compound's coordination chemistry to improve tracer stability and targeting efficiency in diagnostics.

Medical Applications

Mechanism of Action

Gallium nitrate exerts its biological effects primarily through the trivalent (Ga³⁺), which closely mimics the and coordination chemistry of ferric iron (Fe³⁺). This similarity allows Ga³⁺ to bind to , the iron-transport protein, thereby competing with Fe³⁺ for cellular uptake via receptor-mediated . Once inside the cell, Ga³⁺ disrupts iron homeostasis by accumulating in iron-rich compartments, leading to iron deprivation that impairs the function of iron-dependent enzymes. A key target of this iron mimicry is , an essential for converting ribonucleotides to , which are building blocks for . Ga³⁺ inhibits by substituting for the iron cofactor at its , thereby reducing deoxyribonucleotide triphosphate (dNTP) pools and halting in rapidly dividing cells. This mechanism contributes to the anti-proliferative effects observed in cancer cells, particularly those with high expression and upregulated activity. In bone tissue, gallium nitrate inhibits osteoclast activity by binding to hydroxyapatite, the primary mineral component of bone, which enhances crystal formation and reduces mineral solubility. This binding stabilizes the bone matrix and decreases the release of calcium and into the bloodstream. Additionally, Ga³⁺ suppresses -mediated by inhibiting acid secretion through the vacuolar-type H⁺-ATPase , without affecting osteoclast recruitment or development. Gallium nitrate also interacts directly with DNA by binding to phosphate groups along the backbone, forming stable complexes that alter DNA structure and inhibit its synthesis. This phosphate coordination destabilizes the DNA helix and interferes with replication processes, further promoting anti-proliferative effects in tumor cells. Recent studies from 2023 to 2025 have explored the antimicrobial potential of gallium nitrate and its derivatives against multidrug-resistant (MDR) pathogens, leveraging the same iron-mimicry mechanism to disrupt bacterial iron acquisition and metabolism. For instance, gallium nitrate potentiates colistin activity against MDR Klebsiella pneumoniae by inducing reactive oxygen species accumulation under iron-limiting conditions, while pH-dependent formulations enhance efficacy against Pseudomonas aeruginosa biofilms. Emerging gallium-based nanoparticles further show promise in reducing bacterial burdens in MDR infections, including mycobacteria, by inhibiting iron-dependent enzymes like ribonucleotide reductase and aconitase.

Clinical Indications and Efficacy

Gallium nitrate is primarily indicated for the treatment of cancer-associated hypercalcemia that is unresponsive to hydration, a common complication in patients with advanced malignancies such as squamous cell carcinomas, , and . It effectively reduces serum calcium levels by inhibiting osteoclast-mediated , leading to normocalcemia in 72% to 82% of patients within a few days of treatment. This efficacy has been demonstrated in randomized controlled trials, where gallium nitrate outperformed comparators like etidronate, achieving normocalcemia in 82% of cases compared to 43%. The U.S. approved gallium nitrate in 1991 based on phase III trials establishing its superiority over etidronate for acute control of hypercalcemia. Despite its proven effectiveness, its clinical adoption has been limited in recent decades due to the availability of bisphosphonates like pamidronate and , which offer similar or superior efficacy with potentially better tolerability profiles, and the drug's discontinuation from the U.S. market in 2012. Investigational applications of gallium nitrate have focused on its antineoplastic activity, particularly in bladder carcinoma and non-Hodgkin lymphoma. In phase II trials for advanced bladder cancer, it showed modest response rates of 17% to 31% as a single agent in pretreated patients, with partial responses observed after continuous infusion regimens. For non-Hodgkin lymphoma, phase II studies reported overall response rates of approximately 43% in relapsed or refractory cases, including complete and partial remissions, particularly when administered via continuous intravenous infusion. While no major trials have been reported from 2023 to 2025, phase 2 clinical trials have investigated gallium nitrate for nontuberculous mycobacterial (NTM) infections in (CF) patients. For example, NCT02354859 evaluated its efficacy in improving pulmonary function, showing a 5% or greater relative improvement in forced expiratory volume, while NCT04294043 assessed and tolerability of two 5-day IV infusion cycles in adults with CF and NTM. As of 2025, these trials indicate potential antimicrobial applications, with preliminary data supporting its use in iron-limited conditions to disrupt bacterial metabolism. Preclinical and early-phase proposals also suggest potential in managing bone metastases through , leveraging its bone-stabilizing effects to inhibit osteolysis without the need for hospitalization.

Pharmacology and Administration

Dosage Forms and Regimens

Although commercially discontinued in , the Ganite formulation of nitrate was an intravenous injection solution, formulated as a clear, colorless, sterile containing 25 mg/mL of gallium (anhydrous basis) in single-use 20 mL vials (500 mg/vial). The standard regimen for treating cancer-related hypercalcemia involved a continuous intravenous of 200 mg/m² per day for 5 consecutive days, administered over 24 hours after dilution in 1,000 mL of 0.9% or 5% dextrose injection. For milder cases, a reduced dose of 100 mg/m² per day for 5 days may be used, with therapy discontinued if serum calcium levels normalize earlier. Adequate hydration was essential, typically achieved with intravenous saline to maintain a output of at least 2 L/day before and during treatment, though overhydration should be avoided in patients with cardiovascular compromise. Dose adjustments were required for renal impairment; therapy should be discontinued if serum exceeds 2.5 mg/dL, and renal function must be monitored closely throughout. The formulation included dihydrate (28.75 mg/mL) and was adjusted to a pH of 6.0-7.0 using or . Investigational approaches included low-dose , such as 0.25-0.5 mg/kg/day for 14 days in cycles, explored for maintenance therapy in conditions like bone metastases. As of 2025, gallium nitrate may be used in clinical trials, such as for intravenous administration in patients with and nontuberculous mycobacterial infections.

Pharmacokinetics and Monitoring

Gallium nitrate was administered exclusively via intravenous , as it exhibits negligible oral . Upon IV administration, whether as a brief 15- to 30-minute or a continuous 24-hour over 5 to 7 days, the drug achieved steady-state plasma concentrations within 24 to 48 hours at typical doses of 200 mg/m²/day. It rapidly distributed throughout the body, primarily binding to plasma for transport, with significant accumulation in bone tissue and tumor cells via receptor-mediated uptake. The of gallium nitrate follow a biphasic elimination pattern, characterized by an initial distribution phase half-life of 8 to 26 minutes and a longer terminal elimination phase half-life ranging from 6 to 196 hours, the latter reflecting prolonged retention in due to its affinity for and incorporation into skeletal structures. Gallium nitrate is not metabolized by the liver or kidneys and is primarily excreted unchanged via the renal route, with approximately 69% eliminated in the within 24 hours and up to 91% within 48 hours; adequate hydration and osmotic diuretics like can enhance early urinary excretion to mitigate . Clinical monitoring during gallium nitrate therapy was essential to prevent renal and electrolyte disturbances. Serum creatinine, calcium, phosphorus, and other electrolytes should be assessed daily or at least twice weekly, with treatment discontinuation recommended if serum creatinine exceeds 2.5 mg/dL or if significant hypocalcemia develops. Dosage adjustments for renal impairment may be necessary, as referenced in administration guidelines. Concurrent administration with other nephrotoxic agents, such as aminoglycosides or amphotericin B, substantially increases the risk of acute renal failure and should be avoided or closely supervised with enhanced hydration.

Safety and Adverse Effects

Renal and Hematologic Toxicity

Gallium nitrate is associated with renal toxicity, manifesting primarily as acute kidney injury or impaired renal function, with an incidence of approximately 12.5% in patients receiving continuous intravenous infusion for hypercalcemia treatment. This toxicity is dose-limiting, particularly when administered as a brief intravenous infusion over 30 minutes at doses of 400–700 mg/m², leading to elevations in serum creatinine and blood urea nitrogen. Mechanisms include direct tubular damage from gallium precipitates that occlude renal tubular lumina, as observed in preclinical rat studies, compounded by dehydration in clinical settings. Early clinical trials reported two cases of acute renal failure among patients receiving gallium nitrate, highlighting the need for caution. Due to this risk, gallium nitrate is contraindicated in patients with severe renal impairment, defined as serum creatinine greater than 2.5 mg/dL. Hematologic toxicity from gallium nitrate primarily involves the development of , particularly in high-dose regimens. This anemia arises from gallium's interference with iron metabolism, mimicking iron to suppress and inhibit production in erythroid precursors. Unlike other chemotherapeutics, gallium nitrate does not typically suppress platelet or counts, making it suitable for patients with preexisting cytopenias. To mitigate renal toxicity, pre-hydration with normal saline is recommended prior to and during to maintain adequate fluid status and reduce the risk of dehydration-related exacerbation. Given the discontinuation of Ganite in , no significant updates on the incidence of these toxicities have emerged from clinical studies between 2023 and 2025. Monitoring for renal and hematologic effects, including serial serum and levels, is essential during therapy.

Cardiovascular and Other Effects

Gallium nitrate administration is associated with decreases in mean systolic and diastolic , typically observed several days after treatment initiation in patients with cancer-related hypercalcemia. These reductions are generally and do not require specific intervention, resolving spontaneously following discontinuation of the infusion. occurs rarely, though has been reported in some cases. Other notable adverse effects include and , which are more likely with rapid intravenous infusion or doses exceeding the recommended 200 mg/m² daily. These gastrointestinal symptoms are usually mild and infrequent but can be managed supportively. is a common disturbance, occurring in up to 79% of patients in controlled trials, with approximately 46% experiencing severe reductions in serum levels below 1.5 mg/dL; supplementation may be necessary to mitigate risks such as or respiratory compromise. Long-term data on cardiac impacts remain limited, with no dedicated studies on chronic cardiovascular outcomes identified beyond 2003. Given the discontinuation of Ganite in 2012, recent investigations from 2023 to 2025 focusing on prolonged exposure effects are absent, highlighting a gap in understanding sustained risks.

Overdose and Management

Symptoms of Overdose

Overdose of gallium nitrate, typically occurring with doses exceeding the recommended 200 mg/m²/day or rapid intravenous infusion, manifests primarily through exacerbated forms of its known adverse effects, with heightened severity distinguishing it from routine therapeutic exposures. Acute symptoms include severe and , often occurring shortly after administration due to the drug's impact on gastrointestinal function and overall profile. These gastrointestinal disturbances are more intense in overdose scenarios compared to standard dosing, where they may be mild or absent. Additionally, profound can develop rapidly, leading to symptoms such as muscle cramps, paresthesias, , and potentially life-threatening cardiac arrhythmias, as the drug's potent inhibition of calcium resorption becomes unchecked. At doses greater than 300 mg/m²/day, as observed in early phase I and II clinical trials, toxicity escalates significantly, with renal insufficiency emerging as a critical acute risk; this includes marked elevations in serum creatinine and , potentially progressing to if not addressed promptly. Case reports from these trials highlight that such elevated dosing regimens consistently produce renal functional abnormalities, contrasting with the milder, reversible effects seen at therapeutic levels. has been associated with very high doses up to 1400 mg/m², though hematologic toxicity remains relatively minimal at lower thresholds. While severe renal toxicity can occur in overdose, particularly in patients with pre-existing renal compromise, it is generally reversible upon discontinuation and appropriate supportive care, though patients require close monitoring to prevent complications. Hematologic effects, such as , are typically not sustained beyond acute resolution. These manifestations underscore the narrow therapeutic window of gallium nitrate, with trial data emphasizing the need for strict dose adherence to mitigate such severe consequences.

Treatment Protocols

In the event of gallium nitrate overdose or severe , the must be discontinued immediately to halt further exposure. Aggressive intravenous hydration is then initiated, typically administering 2-3 L of normal saline per day with or without , to enhance urinary excretion of and mitigate renal damage; this supportive hydration continues for 2-3 days while monitoring renal function and urinary output closely. Supportive care focuses on addressing specific toxicities, such as providing short-term calcium supplementation (e.g., oral ) for symptomatic and transfusions for severe observed at high doses. Serum calcium levels should be monitored throughout to guide supplementation and prevent complications like neuromuscular irritability. These measures are essential, particularly in patients presenting with symptoms of overdose such as , , or acute renal impairment. For cases involving severe renal failure unresponsive to hydration, may be employed to remove and manage , with patients requiring monitoring for 2-3 days post-exposure to assess recovery. These protocols, established in clinical studies from the , remain the standard as of 2025 based on historical data, reflecting the drug's discontinuation in and limited subsequent use.

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