Oxolinic Acid (2-5 ug/mL) suppresses 115 strains of E. Coli[1]. Of the 44 Proteus mirabilis strains, oxolinic acid (0–31 ug/mL) inhibits 94% of them [1]. Oxolinic Acid inhibits all strains of Streptococcus (>5 ug/mL). faecalis enterococcus [1]. Two wild-type E. Coli K-12 strains studied, DM4100 and NI747, showed reduced chromosomal DNA supercoiling in response to oxolinic acid (>2 ug/mL) [2]. In E. coli, olinic acid can limit RNA synthesis and lessen chromosomal DNA supercoiling [2].

Oxolinic Acid (32 mg/kg; intraperitoneal injection) promotes hyperactivity in mice [3].

Animal/Disease Models: Male Swiss albino CD1 mouse (22-25 g) [3]
Doses: 16 mg/kg, 32 mg/kg, 64 mg/kg, 128 mg/kg
Route of Administration: intraperitoneal (ip) injection
Experimental Results: Stimulated mice horizontal activity, peaking at a dose of 32 mg/kg but disappearing at the highest dose tested, 128 mg/kg.

Absorption, Distribution and Excretion
Following human ingestion of orsolini acid (5-ethyl-5,8-dihydro-8-oxo-1,3-dioxacyclopentene-[4,5-γ]quinoline-7-carboxylic acid), trace amounts of bioactive and unidentified orsolini acid complexes were present in urine, but no altered orsolini acid was detected. Following oral administration of the antibacterial agent (14)C-orsolini acid, 24-hour urinary and fecal excretion rates were 27% and 41% in rats, 19% and 14% in dogs, and 49% and 37% in rabbits, respectively. 35% and 10% of human patients received the drug. Peak plasma concentrations of (14)C were reached after 4 hours in dogs and humans, and after 6 hours in rats and rabbits. Following oral administration… rapid absorption from the gastrointestinal tract. Peak serum concentrations of the bioactive unbound drug were reached within 2–4 hours, ranging from 1.8–3.6 μg/ml. Serum concentrations were low during the first 3 days of administration, indicating slow distribution… The protein binding rate of the drug is approximately 77-81%. One study involved 10 healthy women and administered 750 mg twice daily for 7 days. When taken with food, excretion was delayed by 6 hours, but the 48-hour recovery time was not reduced. For more complete data on the absorption, distribution, and excretion of oxooctanoic acid (6 metabolites), please visit the HSDB records page.

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Metabolism/Metabolites
In rats, rabbits, and dogs, it produces 1-ethyl-1,4-dihydro-7-hydroxy-6-methoxy-6-oxoquinoline-3-carboxylic acid; in rats, rabbits, and dogs, it produces oxooctanoyl-β-D-glucuronic acid; CREW, MC, MELGAR, MD, HAYNES, LJ, GALA, RL, & DICARLO, FJ, XENOBIOTICA, 1, 193 (1971). /Excerpt from Table/
The main urinary metabolite is a glucuronide of oxacyclohexane acid…This compound is biologically active, while the glucuronides of almost all drugs are biologically inactive…

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Biological Half-Life
After repeated administration, a biphasic excretion pattern was observed. The initial phase was rapid, with a half-life of approximately 1.5 hours, followed by a slow phase with a half-life of approximately 15 hours. In patients with normal renal function, the concentration of unbound drugs in urine ranges from 15 to 155 UG/ML.

Interactions
Orsolini acid antagonizes the hypnotic effect of sodium barbital in mice and rats. Alpha-methyltyrosine, pimozide, rixaprine, and diazepam antagonize the effects of orsolini acid.

[1]. The antibacterial and pharmacological activity of oxolinic acid (Prodoxol). J Antimicrob Chemother. 1975 Sep;1(3):311-5.

[2]. Inhibition of RNA synthesis by oxolinic acid is unrelated to average DNA supercoiling. J Bacteriol. 1983 Jul; 155(1): 420-423.

[3]. Behavioural and neurochemical evidence that the antimicrobial agent oxolinic acid is a dopamine uptake inhibitor. Eur Neuropsychopharmacol. 1998 Dec;8(4):255-9.

Oxolinic acid is a quinoline monocarboxylic acid with a carboxyl group at position 7, an oxo group and an ethyl group at positions 4 and 1, respectively, and a dioxacyclopentene ring fused at positions 5 and 6. It is a synthetic antibiotic used in veterinary medicine to treat bacterial infections in cattle, pigs, and poultry. It possesses multiple effects, including anti-infective, antibacterial, enzyme inhibitory, antimicrobial, and antifungal activity. Oxolinic acid is a quinoline monocarboxylic acid, an organic heterocyclic compound, an aromatic carboxylic acid, an oxoheterocyclic compound, and a quinolone antibiotic. It is the conjugate acid of Oxolinic acid. Oxolinic acid has been reported in the Chinese honeybee (Apis cerana), and relevant data exist. The basic structure of quinolone antibiotics is nalidixic acid, but nalidixic acid has limited therapeutic value. However, the development of fluoroquinolone drugs has spurred the emergence of novel derivatives with broad-spectrum antibacterial activity. DNA gyrase and topoisomerase IV are both targets of quinolone drugs. A synthetic antibacterial drug related to nalidixic acid is used to treat urinary tract infections. See also: Sodium oxolinate (its active ingredient). Mechanism of Action: ...interferes with deoxyribonucleic acid (DNA) synthesis. However, oxolinate has a 10-fold greater ability to inhibit DNA replication than nalidixic acid, consistent with its stronger in vitro activity against Enterobacteriaceae. Therapeutic Uses: Anti-infective, quinolone; anti-infective drugs, urinary system. The chemical structure, mechanism of action, antibacterial spectrum, and potential toxicity of this drug are similar to nalidixic acid. For penicillin-sensitive or cephalosporin-sensitive adult patients with recurrent urinary tract infections (without bacteremia) caused by susceptible Escherichia coli or Proteus mirabilis, oxolinate is an alternative therapy. ...In vitro studies have shown that this drug is active against most Gram-negative aerobic bacilli that cause bacterial urinary tract infections. Most Escherichia coli, Klebsiella spp., Enterobacteriaceae spp., and Proteus spp. are sensitive to this product. ...Salmonella, Shigella, and Neisseria (Neisseria meningitidis, Neisseria gonorrhoeae) are sensitive to this product...Staphylococcus aureus...
For more complete therapeutic use data on oxadiazine (6 types in total), please visit the HSDB record page.

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Drug Warnings
Pseudomonas aeruginosa and Acinetobacter calcium acetate (Lviv variant and nitrified variant) are both resistant...
Bacterial resistance, once developed...usually progresses rapidly. Therefore, if subsequent cultures show that urine has not reached a sterile state within 48-72 hours, treatment may be considered a failure, as the microorganisms have already developed resistance. Cross-resistance to nalidixic acid has been reported.
...It has a stimulating effect on the central nervous system and should not be prescribed to patients known to have epilepsy.
...It has a narrow antibacterial spectrum; therefore, bacterial culture and susceptibility testing should generally be performed before use. For more complete data on drug warnings (7 in total) for oxolinic acid, please visit the HSDB records page.

C13H11NO5

261.2301

261.063

14698-29-4

Oxolinic acid-d5;1189890-98-9

4628

White to off-white solid powder

1.5±0.1 g/cm3

473.2±45.0 °C at 760 mmHg

314-316°C (dec.)

240.0±28.7 °C

0.0±1.2 mmHg at 25°C

1.638

1.43

1

6

2

19

446

0

KYGZCKSPAKDVKC-UHFFFAOYSA-N

InChI=1S/C13H11NO5/c1-2-14-5-8(13(16)17)12(15)7-3-10-11(4-9(7)14)19-6-18-10/h3-5H,2,6H2,1H3,(H,16,17)

5-ethyl-8-oxo-[1,3]dioxolo[4,5-g]quinoline-7-carboxylic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~1 mg/mL (~3.83 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)