Novobiocin

612.628

612.62

206-146-3

17EC19951N

DTXSID3041083

C705

Pale yellow orthorhombic crystals from ethanol

2941906000

196

4.1

1.3448 g/cu cm

152-154 °C

848.2±65.0 °C at 760 mmHg

466.8±34.3 °C

1.640

H2O: Insoluble

4.9X10-27 mm Hg at 25 deg C (est)

D24 -63.0° (c = 1 in ethanol)

Henry's Law constant = 1.3X10-28 atm-cu m/mol at 25 °C (est)

4.3|pKa1 = 4.3 (coumarin hydroxyl)

Mol wt: 634.60. Minute crystals, dec 220 °C. Specific optical rotation at 24 °C for D (sodium) line = -38 deg (c = 2.5 in 95% ethanol); Specific optical rotation at 24 °C for D (sodium) line = -33 deg (c = 2.5 in water). Freely sol in water. A 100 mg/ml soln has a pH of 7.5 and a half-life of about 30 days at 25 °C and several months at 4 °C /Monosodium salt/|Hydroxyl radical reaction rate constant = 2.7X10-10 cu cm/molecule-sec at 25 °C (est)|Ozone reaction rate constant = 4.5X10-16 cu cm/molecule-sec at 25 °C (est)

NONH for all modes of transport

3

P280-P301 + P312 + P330

H302-H317

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed discontinued drug products for human use, incl novobiocin sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Novobiocin sodium/|Intramammary dosage form. Novobiocin oil suspension. ... Indications for use: It is used in dry cows for the treatment of mastitis caused by susceptible strains of Staphylococcus aureus and Streptococcus agalactiae. ... Indications for use: Use in lactating cows for treatment of mastitis caused by susceptible strains of Staphylococcus aureus.|Tolerances for residues of novobiocin are established at 0.1 part per million in milk from dairy animals and 1 part per million in the uncooked edible tissues of cattle, chickens, turkeys, and ducks|New animal drugs for use in animal feeds. Requirement of a medicated feed mill license. Novobiocin is included on this list.|For more FDA Requirements (Complete) data for NOVOBIOCIN (6 total), please visit the HSDB record page.

|Warning|H317 (97.58%): May cause an allergic skin reaction [Warning Sensitization, Skin]|P261, P264, P272, P280, P302+P352, P305+P351+P338, P321, P333+P313, P337+P313, P363, and P501|Aggregated GHS information provided by 207 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

95%

For the treatment of infections due to staphylococci and other susceptible organisms

Mesh Heading: anti-bacterial agents, enzyme inhibitors|MEDICATION (VET): Used to treat canine respiratory infections and prevent mastitis in dairy cattle.|THERAP CAT: Antibacterial.|THERAP CAT (VET): Antimicrobial|Novobiocin is a narrow-spectrum antibiotic that may be bacteriostatic or bactericidal at higher concentrations. It is active mostly against gram-positive bacteria but also against a few gram-negative bacteria. ... Its main use is in combination with other agents for the treatment of bovine mastitis.

Consequential organ system manifestations associated with ...Novobiocin /include:/ Immune system- skin rash; GI system- nausea, vomiting, diarrhea; hematologic system- pancytopenia, hemolytic anemia. /from table/

Novobiocin is an aminocoumarin antibiotic that was produced by the actinomycete Streptomyces niveus. Novobiocin binds to DNA gyrase, and blocks adenosine triphosphatase (ATPase) activity. Other antibiotics in the aminocoumarin class include coumermycin A1 and clorobiocin.

Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)|Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)|Compounds that inhibit cell production of DNA or RNA. (See all compounds classified as Nucleic Acid Synthesis Inhibitors.)

Oral bioavailability is negligible.|Patients with refractory cancer were treated with VP-16 on days 1, 3, and 5 /in a Phase 1 Clinical Trial/. Antiemetics, consisting of ondansetron and dexamethasone, were given 60 minutes before the VP-16 was administered. Novobiocin was given orally 30 minutes before the VP-16, and the dose was escalated in successive groups of patients according to a standard dose escalation design. Treatment cycles were repeated every 4 weeks. Plasma concentrations of novobiocin were determined during the first treatment cycle by high-performance liquid chromatography. Thirty-three patients were treated for a total of 69 cycles. Eleven patients were treated with a starting dose of VP-16 of 120 mg/sq m, and three of these patients experienced neutropenic fever. The dose of VP-16 was reduced to 100 mg/m2, and an additional 22 patients were enrolled. The dose of novobiocin ranged from 3 to 9 g. At a novobiocin dose of at least 5.5 g, plasma concentrations of at least 150 uM were sustained for 24 hours.

6 hours|Novobiocin was given p.o. for 96 hr; 750 mg/sq m of i.v. cyclophosphamide was administered at 48 hr. Thirty-four patients received 65 courses. ... 18 of 19 patients treated at greater than or equal to 4 g daily had serum levels greater than or equal to 100 ug/ml at steady state, a level which corresponds to levels used in vitro and seen in vivo where the murine novobiocin half-life of 82 min is far less than that seen in humans (6.0 hr).

Novobiocin is an aminocoumarinthat works by inhibiting the GyrB subunit of the bacterial DNA gyrase enzyme involved in energy tranduction. Similar to other aminocoumarin antibiotics, it acts as a competitive inhibitor of the ATPase reaction catalysed by GyrB.

/SIGNS AND SYMPTOMS/ Patients with refractory cancer were treated with VP-16 on days 1, 3, and 5 /in a Phase 1 Clinical Trial/. Antiemetics, consisting of ondansetron and dexamethasone, were given 60 minutes before the VP-16 was administered. Novobiocin was given orally 30 minutes before the VP-16, and the dose was escalated in successive groups of patients according to a standard dose escalation design. Treatment cycles were repeated every 4 weeks. Plasma concentrations of novobiocin were determined during the first treatment cycle by high-performance liquid chromatography. Thirty-three patients were treated for a total of 69 cycles. Eleven patients were treated with a starting dose of VP-16 of 120 mg/m2, and three of these patients experienced neutropenic fever. The dose of VP-16 was reduced to 100 mg/sq m, and an additional 22 patients were enrolled. The dose of novobiocin ranged from 3 to 9 g. At a novobiocin dose of at least 5.5 g, plasma concentrations of at least 150 uM were sustained for 24 hours. Dose-limiting toxicities consisted of neutropenic fever and reversible hyperbilirubinemia. Nausea, which was a limiting toxicity in other trials of novobiocin, was well controlled with the use of serotonergic antiemetics. Diarrhea was common but mild in most patients. In previously treated patients, the recommended dose of novobiocin in this schedule is 7 g/sq m/day. Novobiocin does not appear to augment the toxicity of VP-16 to the bone marrow or the gastrointestinal mucosa. Plasma concentrations of novobiocin equivalent to the levels required to modulate VP-16 in vitro are readily achievable for total but not unbound free drug.|/SIGNS AND SYMPTOMS/ Antineoplastic drug resistance is a major obstacle to improved treatment of most adult cancers in humans. Novobiocin, an antibacterial agent which inhibits the eukaryotic topoisomerase II enzyme, increases the cytotoxicity of several alkylating agents in vitro by the formation of lethal DNA-DNA interstrand cross-links, perhaps by decreasing the repair of drug monoadducts. In murine tumors treated in vivo novobiocin markedly potentiates alkylating agent cytotoxicity without concomitant increases in host toxicity. With this background, a Phase I trial of novobiocin and cyclophosphamide was performed in refractory cancer patients. Novobiocin was given p.o. for 96 h; 750 mg/m2 of i.v. cyclophosphamide was administered at 48 hr. Thirty-four patients received 65 courses. The dose-limiting toxicity of novobiocin in this trial was vomiting. The maximum tolerated dose was 6 g/day. Six of 34 patients had Grade III or IV mylosuppression but no dose escalation effect was noted. Three patients developed allergic reactions which resolved completely. No other significant toxicity occurred. While no dose-dependent effect on serum novobiocin levels occurred, 18 of 19 patients treated at greater than or equal to 4 g daily had serum levels greater than or equal to 100 ug/ml at steady state, a level which corresponds to levels used in vitro and seen in vivo where the murine novobiocin half-life of 82 min is far less than that seen in humans (6.0 hr). Two of 30 evaluable patients had partial responses. Four other patients had stable disease. Four of six had prior disease progression on cyclophosphamide combination therapy. Novobiocin is well tolerated in patients receiving cyclophosphamide and blood levels are in the drug-potentiating range. Phase II trials in cyclophosphamide refractory patients are anticipated.

Calcium, Novobiocin

Analyte: novobiocin; matrix: chemical identification; procedure: thin-layer chromatography with comparison to standards /novobiocin sodium/|Analyte: novobiocin; matrix: chemical purity; procedure: cylinder-plate method or turbidimetric method with comparison to standards /novobiocin sodium/|Analyte: novobiocin; matrix: pharmaceutical preparation (intramammary infusion); procedure: cylinder-plate method or turbidimetric method with comparison to standards (chemical purity) /novobiocin sodium/|Analyte: novobiocin; matrix: pharmaceutical preparation (oil); procedure: high-performance liquid chromatography with ultraviolet detection at 340 nm; limit of detection: 10 ng

Analyte: novobiocin; matrix: blood (plasma); procedure: reversed-phase high-performance liquid chromatography with ultraviolet detection at 254 nm|Analyte: novobiocin; matrix: blood (serum); procedure: high-performance liquid chromatography with ultraviolet detection at 340 nm; limit of quantitation: 1 ug/mL|Analyte: novobiocin; matrix: blood (serum), milk, tissue (muscle, liver, kidney); procedure: high-performance liquid chromatography with ultraviolet detection at 340 nm; limit of detection: 10 ppb|Analyte: novobiocin; matrix: milk; procedure: high-performance liquid chromatography with ultraviolet detection at 340 nm; limit of detection: <0.05 ppm|Analyte: novobiocin; matrix: milk; procedure: high-performance liquid chromatography with ultraviolet detection at 293 nm; limit of detection: 4 ppb

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