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Gallium nitrate

Gallium nitrate is an inorganic compound with the chemical formula Ga(NO₃)₃, typically encountered as a white crystalline powder or hydrate form, highly soluble in water and exhibiting a melting point around 110°C where it decomposes.^[1]^[2] It serves primarily as a pharmaceutical agent, administered intravenously to treat hypercalcemia of malignancy by inhibiting osteoclast-mediated bone resorption, thereby reducing elevated serum calcium levels in cancer patients.^[3]^[4] As a trivalent salt of gallium, a heavy metal with chemical similarities to iron, gallium nitrate binds to transferrin and accumulates in bone tissue, where it suppresses bone turnover and exhibits anti-inflammatory effects by inhibiting cytokines like IL-1β and matrix metalloproteinases.^[3]^[5] Its antineoplastic properties have been demonstrated in clinical trials, showing response rates of up to 30% in relapsed non-Hodgkin's lymphoma and activity against urothelial cancers, though it is no longer commercially available following the discontinuation of the brand Ganite in 2012.^[4]^[6] Beyond oncology, gallium nitrate has been investigated for treating bone disorders such as Paget's disease, osteoporosis, and multiple myeloma due to its ability to modulate calcium homeostasis and reduce pathological bone resorption, with renal excretion as its primary elimination route and nephrotoxicity as a key dose-limiting side effect. It has also been investigated in clinical trials for cystic fibrosis patients with chronic infections, such as those caused by Pseudomonas aeruginosa or nontuberculous mycobacteria.^[2]^[7]^[8] In non-medical applications, it acts as a precursor for synthesizing gallium-based materials like gallium oxide, leveraging its solubility and reactivity in aqueous solutions.^[9]

Physical and Chemical Properties

Molecular Structure

Gallium nitrate has the chemical formula Ga(NO₃)₃, consisting of a gallium(III) cation and three nitrate anions. It is most commonly isolated and used in the form of its nonahydrate, Ga(NO₃)₃·9H₂O, which incorporates nine molecules of water of hydration.^[1]^[10] The Ga³⁺ ion possesses a high charge-to-radius ratio, with an ionic radius 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 nitrate groups or water molecules.^[11]^[12] Due to its similar charge and ionic radius to Fe³⁺ (64 pm), Ga³⁺ exhibits analogous coordination behavior, forming stable octahedral complexes with oxygen donors like nitrate, which can act as monodentate or bidentate ligands depending on the environment.^[11]^[12] 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.^[10]

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.^[13] The nonahydrate exhibits a melting point of approximately 110 °C, though it undergoes decomposition rather than a true phase change at this temperature. The anhydrous form decomposes prior to melting, preventing observation of a distinct melting behavior. It lacks a defined boiling point, instead decomposing at elevated temperatures without entering a liquid phase.^[14] Under standard laboratory conditions of temperature and pressure, gallium nitrate hydrate 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.^[15]

History

Discovery of Gallium

Gallium was discovered in 1875 by the French chemist Paul-Émile Lecoq de Boisbaudran through spectroscopic examination of a zinc blende (sphalerite) ore sample from the Pyrenees.^[16] 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.^[16]^[17] This spectroscopic detection was a landmark in elemental discovery, confirming Mendeleev's periodic law and highlighting the power of emission spectroscopy for identifying trace elements in complex minerals.^[18] Following the spectroscopic identification, Lecoq de Boisbaudran named the new element gallium after "Gallia," the Latin term for France, honoring his homeland; some accounts also note a possible secondary reference to his surname, as "le coq" (rooster) translates to "gallus" in Latin.^[16] To isolate the element, he processed approximately 430 kilograms of zinc blende ore, yielding only about 0.65 grams of impure gallium initially. Early isolation involved dissolving the ore in acids, precipitating gallium as hydroxide, redissolving in hydrochloric acid to form gallium chloride (GaCl₃), and further purifying via fractional precipitation and electrolysis to obtain the metallic form by late 1875.^[16]^[17] These initial efforts produced milligram quantities of gallium chloride mixed with zinc chloride, 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 gallium, achieved in the late 19th century by dissolving the metal in dilute nitric acid, a standard method for forming metal nitrates from reactive elements.^[19] 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 hydrate.^[19] Early studies of gallium nitrate focused on its solubility and stability, confirming gallium's +3 oxidation state and its chemical analogies to aluminum and iron. In its early years, gallium and its nitrate compound saw limited applications, primarily confined to fundamental chemical research on group 13 elements and spectroscopic calibration, as the metal's scarcity—derived from trace impurities in zinc ores—restricted broader exploration until the 20th century.^[20] Notably, the Ga³⁺ ion's ionic radius (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.^[17]

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.^[21] 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.^[22] The development of stable gallium nitrate as a therapeutic agent accelerated in the 1970s, following preclinical studies that identified its antitumor activity in animal models, including inhibition of tumor growth in rats and mice.^[4] Initial clinical trials in the late 1970s and early 1980s evaluated its pharmacokinetics 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 metabolism, with key 1980s publications demonstrating that gallium nitrate inhibits osteoclast-mediated bone resorption and collagen synthesis in vitro, while increasing bone calcium content in vivo.^[23]^[24] 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.^[25] 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.^[26]^[27]

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.^[28] The balanced reaction equation under these conditions is:

\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.^[29] 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.^[28] Purification is accomplished by recrystallization from deionized water, yielding colorless crystals of the nonahydrate form, \text{Ga(NO}_3)_3 \cdot 9\text{H}_2\text{O}, with purities exceeding 99.99% achievable via this bench-scale process.^[29] 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.^[28]

Commercial Production

Commercial production of gallium nitrate begins with high-purity elemental gallium, typically 99.9999% (6N) grade, sourced primarily as a byproduct from the processing of bauxite during aluminum extraction via the Bayer process or from zinc ore refining.^[30]^[31] This gallium is reacted with high-purity nitric acid in large-scale reactors under controlled conditions, such as temperatures of 50–80°C, to form gallium nitrate solution through acid digestion.^[28] The resulting solution undergoes filtration to remove undissolved impurities, followed by concentration via evaporation at 80–100°C and cooling to 0–20°C to promote crystallization 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.^[28]^[13] 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.^[13] 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.^[13] 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.^[13] Purity of the commercial gallium nitrate nonahydrate exceeds 99%, with trace metal impurities minimized to meet pharmaceutical specifications, as verified by techniques such as inductively coupled plasma mass spectrometry (ICP-MS).^[28]^[32] These processes enable efficient, large-volume production while maintaining the compound's stability and efficacy for medical formulations under GMP compliance.^[13]

Chemical Reactivity

Oxidation and Reduction Reactions

Gallium nitrate acts as an oxidizing agent primarily due to the nitrate (NO₃⁻) group, which can oxidize metals or other reducing agents while being reduced to gaseous products such as nitrogen dioxide (NO₂) or nitric oxide (NO).^[33] This reactivity arises from the strong oxidizing nature of the nitrate ion in acidic or neutral conditions, facilitating electron transfer processes where the nitrate accepts electrons to form lower oxidation state nitrogen species.^[34] 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 reduction potential 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 thermal decomposition to gallium oxide as an intermediate step.^[35] For instance, reactions with potent reducers like hydrazine generate significant heat and evolve gases, including nitrogen, as the nitrate is reduced and Ga³⁺ is partially lowered in oxidation state.^[36] 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.^[37] 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.^[37]^[10] Gallium nitrate exhibits violent reactions with cyanides, thiocyanates, and strong reducing agents due to rapid redox interactions that can lead to explosions from heat and gas buildup.^[38] For example, contact with barium thiocyanate or sodium hypophosphite triggers explosive decomposition, emphasizing the need for careful handling to mitigate risks from the oxidizing nitrate moiety.^[38]

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 fire hazards and decomposition.^[14] It is incompatible with metals due to its corrosive nature and should be kept in glass or plastic containers to avoid container degradation.^[39] As an oxidizer, gallium nitrate may intensify fires and is corrosive to metals, posing risks during handling.^[40] Aqueous solutions have a low pH of approximately 2, causing severe skin and eye irritation or burns upon contact.^[39] Inhalation of dust or fumes, particularly nitrogen oxides (NOx) generated during thermal decomposition or certain oxidation/reduction reactions, can irritate the respiratory tract.^[40] Safe handling requires the use of personal protective equipment (PPE), including chemical-resistant gloves, safety goggles, and protective clothing to prevent skin and eye exposure.^[14] Operations should be conducted in a well-ventilated area or under a fume hood to minimize inhalation risks. In case of spills, evacuate the area, contain the material with absorbent pads, and neutralize with a base such as sodium bicarbonate before cleanup to avoid further corrosion or reaction.^[41] Due to its nitrate content, improper disposal of gallium nitrate can contribute to nitrate pollution in water bodies, potentially leading to eutrophication.^[42] 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.^[43]

Industrial Applications

Synthesis of Gallium Nitride

Gallium nitrate serves as a key precursor in the synthesis of gallium nitride (GaN), a wide-bandgap semiconductor material essential for advanced electronics. One prominent method involves a direct current (DC) non-transferred arc plasma reaction, developed in 2016, which utilizes gallium nitrate hydrate (Ga(NO₃)₃·xH₂O) mixed with melamine (C₃H₆N₆) or ammonia (NH₃) as nitrogen sources under high-temperature conditions.^[44] 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 argon as the carrier gas, followed by nitridation and subsequent annealing at 850°C for 3 hours in a vacuum furnace 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 nitrogen oxide (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.^[44] 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 power electronics for high-efficiency devices.^[44] 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 manufacturing and positions the region as a hub for semiconductor innovation as of November 2025.^[45]

Other Manufacturing Uses

Gallium nitrate serves as a key precursor in the synthesis of gallium oxide (Ga₂O₃) polymorphs, including α-, β-, and γ-phases, through controlled precipitation methods. In this process, aqueous solutions of gallium nitrate are mixed with sodium carbonate to form gallium hydroxide intermediates, which are then calcined at varying temperatures to yield the desired oxide forms. This scalable approach is particularly useful for producing materials employed in optoelectronic and high-temperature applications.^[46] 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 alkylation by activating substrates through coordination with gallium's electron-deficient centers, offering advantages in selectivity and recyclability over homogeneous alternatives.^[47]^[48] 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 compound annual growth rate (CAGR) of 25.4% from 2024 to 2025, reflecting increased adoption in high-performance devices.^[49] Emerging applications include the integration of gallium nitrate into nanocarriers for diagnostic purposes, such as gallium-based nanoplatforms that enhance imaging and biosensing capabilities in cancer detection. These systems leverage the compound's coordination chemistry to improve tracer stability and targeting efficiency in medical diagnostics.^[50]

Medical Applications

Mechanism of Action

Gallium nitrate exerts its biological effects primarily through the trivalent gallium ion (Ga³⁺), which closely mimics the ionic radius and coordination chemistry of ferric iron (Fe³⁺).^[51] This similarity allows Ga³⁺ to bind to transferrin, the iron-transport protein, thereby competing with Fe³⁺ for cellular uptake via transferrin receptor-mediated endocytosis.^[51] 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.^[51] A key target of this iron mimicry is ribonucleotide reductase, an enzyme essential for converting ribonucleotides to deoxyribonucleotides, which are building blocks for DNA synthesis.^[51] Ga³⁺ inhibits ribonucleotide reductase by substituting for the iron cofactor at its active site, thereby reducing deoxyribonucleotide triphosphate (dNTP) pools and halting DNA replication in rapidly dividing cells.^[51] This mechanism contributes to the anti-proliferative effects observed in cancer cells, particularly those with high transferrin receptor expression and upregulated ribonucleotide reductase activity.^[51] 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.^[52] This binding stabilizes the bone matrix and decreases the release of calcium and phosphate into the bloodstream.^[52] Additionally, Ga³⁺ suppresses osteoclast-mediated bone resorption by inhibiting acid secretion through the vacuolar-type H⁺-ATPase proton pump, without affecting osteoclast recruitment or development.^[52] 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.^[53] This phosphate coordination destabilizes the DNA helix and interferes with replication processes, further promoting anti-proliferative effects in tumor cells.^[53] 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.^[54] 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.^[54]^[55] 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.^[56]

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, breast cancer, and multiple myeloma. It effectively reduces serum calcium levels by inhibiting osteoclast-mediated bone resorption, leading to normocalcemia in 72% to 82% of patients within a few days of treatment.^[57] 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%.^[58] The U.S. Food and Drug Administration approved gallium nitrate in 1991 based on phase III trials establishing its superiority over etidronate for acute control of hypercalcemia.^[59] Despite its proven effectiveness, its clinical adoption has been limited in recent decades due to the availability of bisphosphonates like pamidronate and zoledronic acid, which offer similar or superior efficacy with potentially better tolerability profiles, and the drug's discontinuation from the U.S. market in 2012.^[60]^[61] 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.^[62] 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.^[63] While no major oncology trials have been reported from 2023 to 2025, phase 2 clinical trials have investigated gallium nitrate for nontuberculous mycobacterial (NTM) infections in cystic fibrosis (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 safety 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.^[64]^[8] Preclinical and early-phase proposals also suggest potential in managing bone metastases through subcutaneous administration, leveraging its bone-stabilizing effects to inhibit osteolysis without the need for hospitalization.^[65]

Pharmacology and Administration

Dosage Forms and Regimens

Although commercially discontinued in 2012, the Ganite formulation of gallium nitrate was an intravenous injection solution, formulated as a clear, colorless, sterile concentrate containing 25 mg/mL of gallium (anhydrous basis) in single-use 20 mL vials (500 mg/vial).^[66]^[6] The standard regimen for treating cancer-related hypercalcemia involved a continuous intravenous infusion of 200 mg/m² per day for 5 consecutive days, administered over 24 hours after dilution in 1,000 mL of 0.9% sodium chloride or 5% dextrose injection.^[66] 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.^[66] Adequate hydration was essential, typically achieved with intravenous saline to maintain a urine output of at least 2 L/day before and during treatment, though overhydration should be avoided in patients with cardiovascular compromise.^[66] Dose adjustments were required for renal impairment; therapy should be discontinued if serum creatinine exceeds 2.5 mg/dL, and renal function must be monitored closely throughout.^[66] The formulation included sodium citrate dihydrate (28.75 mg/mL) and was adjusted to a pH of 6.0-7.0 using sodium hydroxide or hydrochloric acid.^[66] Investigational approaches included low-dose subcutaneous administration, such as 0.25-0.5 mg/kg/day for 14 days in cycles, explored for maintenance therapy in conditions like bone metastases.^[67] As of 2025, gallium nitrate may be used in clinical trials, such as for intravenous administration in patients with cystic fibrosis and nontuberculous mycobacterial infections.^[8]

Pharmacokinetics and Monitoring

Gallium nitrate was administered exclusively via intravenous infusion, as it exhibits negligible oral bioavailability. Upon IV administration, whether as a brief 15- to 30-minute infusion or a continuous 24-hour infusion 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 transferrin for transport, with significant accumulation in bone tissue and tumor cells via transferrin receptor-mediated uptake.^[26] The pharmacokinetics 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 bone due to its affinity for hydroxyapatite 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 urine within 24 hours and up to 91% within 48 hours; adequate hydration and osmotic diuretics like mannitol can enhance early urinary excretion to mitigate nephrotoxicity.^[26]^[68] 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.^[13]

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.^[26] 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.^[26] 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.^[26] Early clinical trials reported two cases of acute renal failure among patients receiving gallium nitrate, highlighting the need for caution.^[13] Due to this risk, gallium nitrate is contraindicated in patients with severe renal impairment, defined as serum creatinine greater than 2.5 mg/dL.^[13] Hematologic toxicity from gallium nitrate primarily involves the development of microcytic anemia, particularly in high-dose regimens.^[26] This anemia arises from gallium's interference with iron metabolism, mimicking iron to suppress erythropoiesis and inhibit hemoglobin production in erythroid precursors.^[26] Unlike other chemotherapeutics, gallium nitrate does not typically suppress platelet or white blood cell counts, making it suitable for patients with preexisting cytopenias.^[26] To mitigate renal toxicity, pre-hydration with normal saline is recommended prior to and during infusion to maintain adequate fluid status and reduce the risk of dehydration-related exacerbation.^[26] Given the discontinuation of Ganite in 2012, no significant updates on the incidence of these toxicities have emerged from clinical studies between 2023 and 2025.^[6] Monitoring for renal and hematologic effects, including serial serum creatinine and hemoglobin levels, is essential during therapy.

Cardiovascular and Other Effects

Gallium nitrate administration is associated with decreases in mean systolic and diastolic blood pressure, typically observed several days after treatment initiation in patients with cancer-related hypercalcemia. These reductions are generally asymptomatic and do not require specific intervention, resolving spontaneously following discontinuation of the infusion. Hypotension occurs rarely, though tachycardia has been reported in some cases.^[13]^[69] Other notable adverse effects include nausea and vomiting, 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. Hypophosphatemia is a common electrolyte disturbance, occurring in up to 79% of patients in controlled trials, with approximately 46% experiencing severe reductions in serum phosphorus levels below 1.5 mg/dL; supplementation may be necessary to mitigate risks such as muscle weakness or respiratory compromise.^[13]^[13] 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.^[6]

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 nausea and vomiting, often occurring shortly after administration due to the drug's impact on gastrointestinal function and overall toxicity profile. These gastrointestinal disturbances are more intense in overdose scenarios compared to standard dosing, where they may be mild or absent. Additionally, profound hypocalcemia can develop rapidly, leading to symptoms such as muscle cramps, paresthesias, tetany, and potentially life-threatening cardiac arrhythmias, as the drug's potent inhibition of bone calcium resorption becomes unchecked.^[66]^[3] 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 BUN, potentially progressing to acute kidney injury 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. Anemia has been associated with very high doses up to 1400 mg/m², though hematologic toxicity remains relatively minimal at lower thresholds.^[70]^[71]^[26] 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 anemia, 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.^[70]^[26]^[66]

Treatment Protocols

In the event of gallium nitrate overdose or severe toxicity, the infusion must be discontinued immediately to halt further exposure.^[66] Aggressive intravenous hydration is then initiated, typically administering 2-3 L of normal saline per day with or without loop diuretics, to enhance urinary excretion of gallium and mitigate renal damage; this supportive hydration continues for 2-3 days while monitoring renal function and urinary output closely.^[66]^[26] Supportive care focuses on addressing specific toxicities, such as providing short-term calcium supplementation (e.g., oral calcium carbonate) for symptomatic hypocalcemia and red blood cell transfusions for severe anemia observed at high doses.^[66] Serum calcium levels should be monitored throughout to guide supplementation and prevent complications like neuromuscular irritability.^[66] These measures are essential, particularly in patients presenting with symptoms of overdose such as nausea, vomiting, or acute renal impairment.^[66] For cases involving severe renal failure unresponsive to hydration, hemodialysis may be employed to remove gallium and manage uremia, with patients requiring monitoring for 2-3 days post-exposure to assess recovery.^[70] These protocols, established in clinical studies from the 1990s, remain the standard as of 2025 based on historical data, reflecting the drug's discontinuation in 2012 and limited subsequent use.^[66]^[69]

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The stable, nonahydrate, Ga(N03)3•9H2O is a white, slightly hygroscopic, crystalline powder of molecular weight 417.87, that is readily soluble in water.
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[PDF] Gallium(III) nitrate hydrate - SAFETY DATA SHEET
Sep 26, 2009 · Gallium(III) nitrate hydrate. Revision Date 28-Mar-2024. 9. Physical and chemical properties. Physical State. Powder Solid. Appearance. White.
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[PDF] Safety Data Sheet: Gallium(III) nitrate hydrate - Carl ROTH
The material is stable under normal ambient and anticipated storage and handling conditions of tem- perature and pressure. 10.3 Possibility of hazardous ...
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Gallium - Element information, properties and uses | Periodic Table
Gallium was discovered in Paris by Paul-Émile Lecoq de Boisbaudran in 1875. He observed a new violet line in the atomic spectrum of some zinc he had ...
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Gallium | Ga (Element) - PubChem - NIH
It was discovered in zinc blende by the French chemist Paul-Emile Lecoq de Boisbaudran in 1875. It was first isolated in 1878 by Lecoq de Boisbaudran and ...
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Paul-Émile Lecoq de Boisbaudran - Britannica
Oct 14, 2025 · French chemist who developed improved spectroscopic techniques for chemical analysis and discovered the elements gallium (1875), samarium (1880), and ...
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[PDF] Gallium - USGS Publications Warehouse
Solid gallium has a low melting temperature (about. 29 degrees Celsius [°C]) and an unusually high boiling point (about 2,204 °C) (table H1), so that gallium is ...
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Timeline: evolution of the studies involving gallium compounds in...
As early as 1931, Levaditi et al. revealed that gallium tartrate could eradicate syphilis in rabbits and trypanosomes in mice [11]. ... ..
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The medical use of gallium radionuclides: a brief history with some ...
The use of gallium radionuclides in nuclear medicine dates back to the late 1940s, following the observation in toxicologic studies that gallium tended to ...
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Gallium nitrate inhibits calcium resorption from bone and is effective ...
To evaluate the mechanism of drug-induced hypocalcemia, we tested the effects of gallium nitrate upon in vitro release of 45Ca++ from explanted fetal rat bones.Missing: metabolism | Show results with:metabolism
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Gallium nitrate inhibits accelerated bone turnover in patients with ...
Laboratory studies have shown that this drug inhibits bone resorption in vitro and that short-term treatment in vivo increases the calcium content of bone. We ...Missing: inhibition 1980s
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Search Orphan Drug Designations and Approvals - FDA
Gallium nitrate injection. Trade Name: Ganite. Marketing Approval Date: 01/17/1991. Approved Labeled Indication: Exclusivity End Date: 01/17/1998. *Exclusivity ...
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Medical Applications and Toxicities of Gallium Compounds - PMC
At least 4 separate clinical trials have demonstrated the anti-lymphoma activity of gallium nitrate administered as a single agent [24–27], while 3 additional ...
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Development of Gallium Compounds for Treatment of Lymphoma ...
Clinical studies have shown gallium nitrate to have significant antitumor activity against non-Hodgkin's lymphoma and bladder cancer, thus indicating that ...
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CN1762825A - Gallium nitrate preparation method - Google Patents
The preparation process includes: dissolving 6N metal gallium in high purity nitric acid at 50-80 deg.c, evaporating the solution at 80-100 deg.c until no bad ...
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[PDF] Condensed Matter and Interphases
Sep 25, 2022 · The interaction between metallic gallium and concentrated nitric acid resulted in the formation of gallium(III) nitrate crystallohydrate with.
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[PDF] Gallium - Mineral Commodity Summaries 2024 - USGS.gov
China reported that its primary low-purity gallium production capacity increased by 250,000 kilograms per year in 2022 to 1,000,000 kilograms per year. This ...
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Gallium | Sources, and Extraction Methods - Quest Metals
Oct 21, 2024 · The primary commercial source of gallium is Bayer liquor, a byproduct of alumina production from bauxite. Gallium is recovered during the alumina refining ...<|control11|><|separator|>
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Gallium Nitrate | AMERICAN ELEMENTS ®
Gallium Nitrate is a highly water soluble crystalline Gallium source for uses compatible with nitrates and lower (acidic) pH.
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GALLIUM NITRATE - CAMEO Chemicals - NOAA
Oxidizing agents, such as GALLIUM NITRATE, can react with reducing agents to generate heat and products that may be gaseous (causing pressurization of closed ...
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https://cameochemicals.noaa.gov/chemical/20429
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[PDF] APPENDIX H Standard Reduction Potentials* - CSUN
Gallium. Ga3+ + 3eJ. T Ga(s). J0.549. 0.61. GaOOH(s) + H2O + 3e. J. T Ga(s) + 3OH. J. J1.320. J1.08. Germanium. Ge2+ + 2eJ. T Ge(s). 0.1. H4GeO4 + 4H+ + 4eJ. T ...Missing: Ga0 | Show results with:Ga0
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How to prepare elemental gallium from a mixture of gallium and ...
Jun 4, 2017 · When you have pure gallium nitrate, decompose it to gallium oxide. Then reduce gallium oxide to gallium using a reducing agent like magnesium.Missing: examples | Show results with:examples
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Thermal decomposition of gallium nitrate hydrate Ga(NO3)3×xH2O
It is concluded that 8 water molecules are present in the hydrate compound. The anhydrous gallium nitrate does not form at any temperature as the reaction ...
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[PDF] Gallium(III) nitrate hydrate - Santa Cruz Biotechnology
Avoid reaction with the following which can cause an explosion: barium thiocyanate, boron phosphide, cyanides, sodium hypophosphite, sulfur and charcoal,.
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[PDF] Gallium(III) nitrate solution, Ga 9-10% w/w - SAFETY DATA SHEET
May 8, 2024 · May be corrosive to metals. Health Hazards. Corrosive. Causes skin and eye burns. Causes serious eye damage. Toxic if inhaled. Environmental ...
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[PDF] Gallium(III) nitrate hydrate - SAFETY DATA SHEET
Sep 8, 2024 · Hazard Statements. H272. May intensify fire; oxidizer. H315. Causes skin irritation. H319. Causes serious eye irritation. Precautionary ...
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[PDF] Gallium (III) Nitrate Hydrate - ProChem, Inc.
SECTION 9 PHYSICAL AND CHEMICAL PROPERTIES. COLOR AND FORM: White crystal. ODOR: None. MOLECULAR WEIGHT: 255.73 (anhy.) BOILING POINT: No data available.<|control11|><|separator|>
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[PDF] Safety Data Sheet: Gallium(III) nitrate hydrate - Carl ROTH
Disposal considerations: see section 13. SECTION 7: Handling and storage. 7.1. Precautions for safe handling. Avoid dust formation. Measures ...
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[PDF] Safety Data Sheet - Ricca Chemical Company
Apr 5, 2025 · Precautions for Safe Handling and Storage Conditions. Store locked up ... Gallium Nitrate Hydrate (CAS # 69365-72-6): "1.0 % de minimis ...
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Thermal Plasma Synthesis of Crystalline Gallium Nitride ... - MDPI
XRD (X-ray diffraction) pattern of product synthesized by thermal plasma; (a) Plasma 1 by Ga(NO3)3∙32H2O and NH3 without C3H6N6; (b) Plasma 2 by Ga(NO3)3∙32H2O ...Missing: nonahydrate | Show results with:nonahydrate
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National innovation centre for Gallium Nitride semiconductors ...
Jun 26, 2025 · The Centre brings advanced GaN manufacturing capabilities to Singapore, positioning local innovators to compete in high-growth global markets ...
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Synthesis and characterization of α-, β-, and γ-Ga2o3 prepared from ...
It can be prepared by heating the residual of evaporated gallium nitrate solution at 200−250 °С. When it is heated above 500 °С, the δ modification transforms ...
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Ga-MCM-41 synthesis and catalytic activity in the liquid-phase ...
In this paper, we report an easy procedure to synthesize acidic Ga-MCM-41 materials, using gallium nitrate and tetraethyl orthosilicate (TEOS) as gallium and ...<|separator|>
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Recent Progress of Ga-Based Catalysts for Catalytic Conversion of ...
Nov 5, 2022 · After mixing a certain amount of TEOS, sodium aluminate, and gallium nitrate ... Lewis acid catalyst for organic synthetic transformations.
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Gallium Market Size And Research Report 2025-2034
Mar 24, 2025 · The market is projected to expand from $2.32 billion in 2024 to $2.91 billion in 2025, representing a compound annual growth rate (CAGR) of 25.4 ...Missing: nitrate | Show results with:nitrate
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Application in cancer therapy, imaging and biosensing - ScienceDirect
The present article deals with the advancement of gallium based nanoplatforms for therapy, imaging, and biosensing of cancers.
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Gallium and Other Main Group Metal Compounds as Antitumor Agents
Apart from the consequences of iron deprivation, gallium exerts cytotoxic effects by direct interaction with the iron-dependent enzyme ribonucleotide reductase ...Missing: mimicry | Show results with:mimicry<|separator|>
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The Effects of Gallium Nitrate on Bone Resorption - PubMed
Gallium does not inhibit the development or recruitment of osteoclasts to bone tissue, unlike many bisphosphonates that may induce osteoclast apoptosis.<|separator|>
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Anticancer redox activity of gallium nanoparticles accompanied with ...
Ga may bind to DNA phosphate group and nucleic bases causing DNA structural modifications, which destabilizes DNA helix. Previous investigations showed that ...
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Gallium Nitrate Enhances Antimicrobial Activity of Colistin against ...
Jun 5, 2023 · We report that gallium nitrate (GaNt), an antimicrobial candidate, exhibits a potentiating effect on colistin against MDR K. pneumoniae clinical isolates.
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pH-mediated potentiation of gallium nitrate against Pseudomonas ...
Sep 24, 2024 · This study focused on the impact of pH on P. aeruginosa resistance to Ga(NO 3 ) 3 , along with the underlying mechanism.
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Gallium Liquid Metal Nanoparticles as Agents to Treat Multidrug ...
Oct 23, 2025 · GaLM NPs have been found to elicit an anti‐inflammatory response without interfering with the ferric homeostasis pathway in immune cells (Zhang ...Missing: integration | Show results with:integration
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Treating cancer-related hypercalcemia with gallium nitrate - PubMed
Gallium nitrate induced normocalcemia in 72% to 82% of patients; in contrast to the comparator agents, it was effective regardless of epidermoid tumor status.
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A randomized double-blind study of gallium nitrate compared with ...
Twenty-eight of 34 patients (82%) who received gallium nitrate achieved normocalcemia compared with 16 of 37 patients (43%) who received etidronate (P less than ...Missing: alternatives | Show results with:alternatives
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Gallium - PharmaKB
Gallium was first approved as Ganite on 1991-01-17. Classification. Small molecule. Drug ...
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Hypercalcemia of Malignancy: An Update on Pathogenesis ... - NIH
[78,79] However, gallium nitrate production was discontinued by the manufacturer in 2012, making it unavailable for the treatment of malignancy-related ...Missing: preference | Show results with:preference
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Quality and Outcomes of Treatment of Hypercalcemia of Malignancy
... bisphosphonates are now the preferred agents for the initial management of hypercalcemia ... gallium nitrate, have largely been replaced by the bisphosphonates.
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Continuous infusion gallium nitrate for patients with ... - PubMed - NIH
Partial responses were observed in 4 of 23 patients (17.4%) who received 350 mg/m2/d or more for 5 days by continuous intravenous infusion. In two additional ...Missing: rate | Show results with:rate
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Gallium nitrate for the treatment of non-Hodgkin's lymphoma - PubMed
Phase I/II studies have shown that gallium nitrate displays the most efficacy ... response rates of 43% in patients with relapsed or refractory NHL. It does ...Missing: bladder | Show results with:bladder
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Gallium nitrate for the treatment of bone metastases - PubMed
The results of randomized double blind studies have suggested that this drug has superior clinical efficacy relative to etidronate, calcitonin, and pamidronate ...Missing: 2023-2025 | Show results with:2023-2025
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Ganite: Package Insert / Prescribing Information - Drugs.com
Mar 25, 2025 · Rapid intravenous infusion of gallium nitrate or use of doses higher than recommended (200 mg/m2) may cause nausea and vomiting and a ...
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Phase 1 Assessment of an Orally Bioavailable Formulation of ...
Clinical studies have shown that low doses of GN (0.25–0.5 mg/kg/day x 14 days) administered by subcutaneous (SC) injection significantly reduced metabolic ...Missing: investigational | Show results with:investigational<|control11|><|separator|>
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The pharmacokinetics of two methods of administration of gallium nitrate were studied: a seven-day continuous intravenous infusion, and a weekly rapid ...
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Gallium nitrate was used to treat cancer-related hypercalcemia. The product was discontinued by the manufacturer in 2012.Missing: regimens | Show results with:regimens
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Clinical toxicologic and pharmacologic studies of gallium nitrate
Pharmacokinetic studies revealed a biphasic half-life, (T 1/2 alpha = 87 minutes and T 1/2 beta = 24.5 hours). Osmotic diuresis reduced the urinary ...
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Phase I-II clinical trial of gallium nitrate (NSC-15200) - PubMed
... dose-limiting renal toxicity was observed at doses exceeding 700 mg/m2. Hematological toxicity was minimal. Ototoxicit …