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
AFTER INGESTION OF OXOLINIC ACID, 5-ETHYL-5,8-DIHYDRO-8 -OXO-1,3-DIOXOLO-[4,5-G]QUINOLINE-7-CARBOXYLIC ACID, BY HUMAN SUBJECTS, URINE CONTAINED SMALL QUANTITY OF BIOLOGICALLY-INACTIVE & UNIDENTIFIED OXOLINIC ACID COMPLEX, BUT NO UNCHANGED OXOLINIC ACID.
OF ORAL DOSE OF ANTIBACTERIAL, (14)C-OXOLINIC ACID, THERE WAS EXCRETED IN 24-HR URINE & FECES RESPECTIVELY, 27 & 41% BY RAT, 19 & 14% BY DOG, 49 & 37% BY RABBIT, & 35 & 10% BY MAN. BLOOD LEVELS OF (14)C PEAKED AFTER 4 HR IN DOG & MAN, & AFTER 6 HR IN RAT & RABBIT.
AFTER ORAL ADMIN...RAPIDLY ABSORBED FROM GI TRACT. PEAK SERUM CONCN OF BIOLOGICALLY ACTIVE UNCONJUGATED DRUG ARE ATTAINED IN 2-4 HR & RANGE FROM 1.8-3.6 UG/ML. LOWER SERUM LEVELS...OCCUR DURING 1ST 3 DAYS OF DOSING, SUGGESTING SLOW DISTRIBUTION... PROTEIN BINDING OF DRUG IS ABOUT 77-81%.
750 MG ADMIN TWICE/DAY FOR 7 DAYS STUDIED IN 10 HEALTHY WOMEN. WHEN TAKEN WITH FOOD, EXCRETION RETARDED BY 6 HR BUT 48 HR RECOVERY NOT DECR.
For more Absorption, Distribution and Excretion (Complete) data for OXOLINIC ACID (6 total), please visit the HSDB record page.

---

Metabolism / Metabolites
YIELDS 1-ETHYL-1,4-DIHYDRO-7-HYDROXY-6-METHOXY-6-OXOQUINOLINE-3-CARBOXYLIC ACID IN RAT, RABBIT, DOG; YIELDS OXOLINOYL-BETA-D-GLUCURONIC ACID IN RAT, RABBIT, DOG; CREW, MC, MELGAR, MD, HAYNES, LJ, GALA, RL, & DICARLO, FJ, XENOBIOTICA, 1, 193 (1971). /FROM TABLE/
MAJOR URINARY METABOLITE WAS GLUCURONIDE OF OXOLINIC ACID...THIS COMPD WAS BIOLOGICALLY ACTIVE WHEREAS ALMOST ALL DRUG GLUCURONIDES ARE BIOLOGICALLY INERT...

---

Biological Half-Life
AFTER REPEATED DOSING, BIPHASIC EXCRETION PATTERN HAS BEEN OBSERVED. INITIAL PHASE IS RAPID WITH T/2 OF ABOUT 1.5 HR, & IS FOLLOWED BY SLOW PHASE WITH T/2 OF ABOUT 15 HR. URINARY CONCN OF UNCONJUGATED DRUG RANGE FROM 15-155 UG/ML IN PT WITH NORMAL RENAL FUNCTION.

Interactions
OXOLINIC ACID ANTAGONIZED HYPNOTIC ACTION OF SODIUM BARBITOL IN MICE & RATS. EFFECTS OF OXOLINIC ACID WERE ANTAGONIZED BY ALPHA-METHYLTYROSINE, PIMOZIDE, RESERPINE, & DIAZEPAM.

[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 quinolinemonocarboxylic acid having the carboxy group at position 7 as well as oxo and ethyl groups at positions 4 and 1 respectively and a dioxolo ring fused at the 5- and 6-positions. A synthetic antibiotic, it is used in veterinary medicine for the treatment of bacterial infections in cattle, pigs and poultry. It has a role as an antiinfective agent, an antibacterial drug, an enzyme inhibitor, an antimicrobial agent and an antifungal agent. It is a quinolinemonocarboxylic acid, an organic heterotricyclic compound, an aromatic carboxylic acid, an oxacycle and a quinolone antibiotic. It is a conjugate acid of an oxolinate.
Oxolinic acid has been reported in Apis cerana with data available.
Quinolone Antibiotic is the basic structure of quinolone is nalidixic acid that has limited therapeutic value. However, the development of fluorinated quinolones led to new derivative compounds with broad antibacterial activity. Both DNA gyrase and topoisomerase IV are targets of quinolones.
Synthetic antimicrobial related to NALIDIXIC ACID and used in URINARY TRACT INFECTIONS.
See also: Sodium Oxolinate (is active moiety of).

---

Mechanism of Action
...INTERFERENCE WITH DEOXYRIBONUCLEIC ACID (DNA) SYNTH. OXOLINIC ACID, HOWEVER, HAS DEMONSTRATED 10-FOLD GREATER /THAN NALIDIXIC ACID/ ABILITY TO INHIBIT DNA REPLICATION, WHICH IS PARALLELED BY ITS GREATER IN VITRO ACTIVITY FOR ENTEROBACTERIACEAE.

---

Therapeutic Uses
Anti-Infective Agents, Quinolone; Anti-Infective Agents, Urinary
DRUG HAS CHEMICAL STRUCTURE, MECHANISM OF ACTION, SPECTRUM OF ACTIVITY & POTENTIAL FOR TOXICITY THAT RESEMBLES NALIDIXIC ACID.
OXOLINIC ACID IS ALTERNATIVE FORM OF THERAPY FOR PENICILLIN-SENSITIVE OR CEPHALOSPORIN-SENSITIVE ADULT WHO HAS RECURRENT URINARY TRACT INFECTION CAUSED BY SUSCEPTIBLE ESCHERICHIA COLI OR PROTEUS MIRABILIS THAT IS NOT COMPLICATED BY BACTEREMIA.
...EXERTS IN VITRO ACTIVITY AGAINST MOST GRAM-NEGATIVE AEROBIC BACILLI THAT CAUSE BACTERIAL URINARY TRACT INFECTIONS. MAJORITY OF ESCHERICHIA COLI, KLEBSIELLA SP, ENTEROBACTER SP & PROTEUS SP ARE SUSCEPTIBLE. ... SALMONELLA, SHIGELLA & NEISSERIA (MENINGITIDIS, GONORRHEAE) ARE SUSCEPTIBLE...STAPHYLOCOCCUS AUREUS...
For more Therapeutic Uses (Complete) data for OXOLINIC ACID (6 total), please visit the HSDB record page.

---

Drug Warnings
PSEUDOMONAS AERUGINOSA & ACINETOBACTER CALCOACETICUS (VAR LIVOFFI & VAR ANITRATUS) ARE UNIFORMLY RESISTANT...
WHEN BACTERIAL RESISTANCE DEVELOPS...IT IS USUALLY RAPID. THEREFORE, IF FOLLOW-UP CULTURES INDICATE THAT URINE IS NOT STERILE WITHIN 48-72 HR, TREATMENT CAN PROBABLY BE CONSIDERED FAILURE SINCE ORGANISM BY THEN WILL HAVE DEVELOPED RESISTANCE. ... CROSS RESISTANCE TO NALIDIXIC ACID HAS BEEN REPORTED.
...HAS STIMULATORY EFFECT ON CNS, & SHOULD NOT BE PRESCRIBED FOR PT WITH KNOWN SEIZURE DISORDERS.
...HAS FAIRLY NARROW ANTIBACTERIAL SPECTRUM &, THEREFORE, BACTERIAL CULTURE & SENSITIVITY TESTS GENERALLY SHOULD BE PERFORMED PRIOR TO ITS USE.
For more Drug Warnings (Complete) data for OXOLINIC ACID (7 total), please visit the HSDB record 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.

---

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).

View More

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)

---

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).

View More

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

---

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.

---

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