Nalidixic acid

232.24

232.24

206-864-7

3B91HWA56M

757432|82174

3249

DTXSID3020912

C47630

PALE BUFF, CRYSTALLINE POWDER|WHITE TO SLIGHTLY YELLOW, CRYSTALLINE POWDER

J - Antiinfectives for systemic use

2933990090

70.5

1.4

White to light yellow Powder

1.3±0.1 g/cm3

229-230 °C

413.1°C at 760 mmHg

203.6±28.7 °C

1.605

H2O: 0.1 G/L (23 ºC);chloroform: 20 mg/mL, clear

0-6°C

LD50 in mice (mg/kg): 3300 orally; 500 s.c.; 176 i.v. (Lesher, 1962)

ODORLESS

8.6None

8.6|PKA 8.6

145.3 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]|141.4 Ų [M+H]+ [CCS Type: TW]|148 Ų [M+H]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]|161.6 Ų [M+Na]+ [CCS Type: TW, Method: calibrated with Waters Major Mix]|145.76 Ų [M+H]+

Insoluble in water.

Acids, Carboxylic

NONH for all modes of transport

2

63-42/43-40-20/21/22-22

22-36/37-45-24-36

QN2885000

Xn

Stable. Incompatible with strong oxidizing agents.

P301 + P312 + P330

H302

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.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

DHHS/NTP; Toxicology & Carcinogenesis Studies of Nalidixic Acid in F344/N Rats and B6C3F1 Mice (Feed Studies) Technical Report Series No. 368 (1989) NIH Publication No. 90-2823

Flash point data for this chemical are not available, but it is probably combustible. (NTP, 1992)

|Danger|H302 (10.2%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P272, P280, P285, P301+P312, P302+P352, P304+P341, P321, P330, P333+P313, P342+P311, P363, and P501|Aggregated GHS information provided by 99 companies from 12 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Fires involving this compound should be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

Excerpt from ERG Guide 151 [Substances - Toxic (Non-combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

SMALL SPILLS AND LEAKAGE: You should dampen the solid spill material with acetone, then transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the adsorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a strong soap and water solution. Do not reenter the contaminate area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

ORAL (LD50): Acute: 1160 mg/kg [Rat]. 572 mg/kg [Mouse]. Toxic psychosis, convulsions, increased intracranial pressure, or metabolic acidosis may occur in patients taking more than the recommended dosage. Vomiting, nausea, and lethargy may also occur following overdosage.

...AT PHYSIOLOGICAL CONCN...NALIDIXIC ACID...DISPLACED SUBSTANTIAL AMT OF WARFARIN FROM HUMAN ALBUMIN BY NON-COMPETITIVE MECHANISM.|SYSTEMIC & URINARY ALKALINIZERS REDUCE ITS EFFECTIVENESS BY INCR ITS EXCRETION RATE. SYSTEMIC EFFECTIVENESS INCR IF URINE IS ACID.|METABOLIC ACIDOSIS WAS INDUCED IN AN 18-YEAR-OLD MALE BY AN OVERDOSE OF NALIDIXIC ACID. SIMULTANEOUS INGESTION OF PROBENECID MAY HAVE ACCENTUATED EFFECT OF INGESTED NALIDIXIC ACID BY PROLONGING ITS SERUM T/2.|Coumarin- or indandione-derivative anticoagulants, especially warfarin and dicumarol, may be displaced from protein-binding sites by nalidixic acid, resulting in increased anticoagulant effect; dosage adjustments may be necessary during and after nalidixic acid therapy.|For more Interactions (Complete) data for NALIDIXIC ACID (6 total), please visit the HSDB record page.

LD50 MOUSE ORAL 3.3 G/KG|LD50 MOUSE SUBCUTANEOUS 0.5 G/KG|LD50 MOUSE INTRAVENOUS 0.176 G/KG|LD50 Rat oral 1160 mg/kg

... Toxicology and carcinogenesis studies were conducted by feeding diets containing nalidixic acid (approximately 99% pure) to groups of F344/N rats and B6C3F1 mice of each sex for ... 2 yr. ... Two yr studies of nalidixic acid were conducted by feeding diets containing 0, 2,000, or 4,000 ppm nalidixic acid to groups of 50 male and 50 female F344/N rats and 50 male and 50 female B6C3F1 mice. Conclusions: Under the conditions of these 2 yr feed studies, there was clear evidence of carcinogenic activity of nalidixic acid for F344/N rats, as indicated by increased incidences of preputial gland neoplasms in males and clitoral gland neoplasms in females. There was equivocal evidence of carcinogenic activity for male B6C3F1 mice fed diets containing nalidixic acid, as indicated by marginally increased incidences of subcutaneous tissue neoplasms There was no evidence of carcinogenic activity for female B6C3F1 mice fed diets containing 2,000 or 4,000 ppm nalidixic acid for 2 yr.

Nalidixic acid is 93% bound to protein in the blood, and the active metabolite, hydroxynalidixic acid is 63% bound.

For the treatment of urinary tract infections caused by susceptible gram-negative microorganisms, including the majority of E. Coli, Enterobacter species, Klebsiella species, and Proteus species.|FDA Label

Anti-Infective Agents, Quinolone /SRP: Antibacterial/|IN US, NALIDIXIC ACID IS APPROVED ONLY FOR TREATMENT OF URINARY TRACT INFECTIONS CAUSED BY SUSCEPTIBLE MICROORGANISMS. EFFECTIVENESS AGAINST INDOLE-POSITIVE PROTEUS IS ESP IMPORTANT. APPARENT CURES...IN 30-50% OF UNCOMPLICATED URINARY TRACT INFECTIONS.|...BRUCELLOSIS HAS BEEN SUCCESSFULLY MANAGED WITH ORAL NALIDIXIC ACID. DRUG HAS BEEN GIVEN IV TO TREAT GRAM-NEGATIVE SEPTICEMIAS.|...BACTERICIDAL TO MOST OF COMMON GRAM-NEGATIVE BACTERIA THAT CAUSE URINARY TRACT INFECTIONS. ...99% OF STRAINS OF E COLI, 98% OF PROTEUS MIRABILIS & 75-97% OF OTHER PROTEUS SPECIES, 92% OF KLEBSIELLA-ENTEROBACTER, & 80% OF OTHER COLIFORM BACTERIA ARE SENSITIVE TO DRUG. ... SOME STRAINS OF SALMONELLA & SHIGELLA...SENSITIVE.|For more Therapeutic Uses (Complete) data for NALIDIXIC ACID (8 total), please visit the HSDB record page.

BECAUSE...MAY ACCUMULATE IN PT WITH RENAL OR HEPATIC INSUFFICIENCY, IT SHOULD BE USED VERY CAUTIOUSLY IN THESE PT, ESP IF NEUROLOGIC DAMAGE IS PRESENT. ... CAUTION IS INDICATED IF THIS DRUG IS USED DURING PREGNANCY, ALTHOUGH SOME... HAVE TAKEN IT DURING 2ND & 3RD TRIMESTERS WITHOUT ADVERSELY AFFECTING MOTHER OR FETUS.|BY ORAL ROUTE IT IS DIFFICULT TO ACHIEVE EFFECTIVE PLASMA LEVELS. FUTHERMORE, BINDING TO PLASMA PROTEIN INHIBITS ACTIVITY. ... 4% THAT PASSES INTO BOWEL IS INSUFFICIENT TO BE EFFICACIOUS IN TREATMENT OF INTESTINAL SHIGELLOSIS...|PSEUDOMONAS SPECIES ARE RESISTANT. ... ACQUIRED RESISTANCE TO DRUG OCCURS, BUT IT DOES NOT SEEM TO BE TRANSFERABLE.|DETERMINATION OF URINARY LEVELS OF 17-KETOSTEROIDS & 17-KETOGENIC STEROIDS MAY BE FALSELY ELEVATED WHEN NALIDIXIC ACID HAS BEEN PRESCRIBED.|For more Drug Warnings (Complete) data for NALIDIXIC ACID (19 total), please visit the HSDB record page.

Nalidixic acid is a quinolone antibacterial agent for oral administration. Nalidixic acid has marked antibacterial activity against gram-negative bacteria including Enterobacter species, Escherichia coli, Morganella Morganii; Proteus Mirabilis, Proteus vulgaris, and Providencia rettgeri. Pseudomonas species are generally resistant to the drug. Nalidixic acid is bactericidal and is effective over the entire urinary pH range. Conventional chromosomal resistance to nalidixic acid taken in full dosage has been reported to emerge in approximately 2 to 14 percent of patients during treatment; however, bacterial resistance to nalidixic acid has not been shown to be transferable via R factor.

Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)|Compounds that inhibit the activity of DNA TOPOISOMERASE II. Included in this category are a variety of ANTINEOPLASTIC AGENTS which target the eukaryotic form of topoisomerase II and ANTIBACTERIAL AGENTS which target the prokaryotic form of topoisomerase II. (See all compounds classified as Topoisomerase II Inhibitors.)

Following oral administration, nalidixic acid is rapidly absorbed from the gastrointestinal tract. Bioavailability is approximately 96%. Absorption may be delayed if taken with antacids.|Following oral administration, NegGram is rapidly absorbed from the gastrointestinal tract, partially metabolized in the liver, and rapidly excreted through the kidneys. Approximately four percent of NegGram is excreted in the feces.|ABSORPTION & ELIMINATION RATES OF NALIDIXIC ACID WERE SHOWN TO BE LOW IN NEWBORN CHILDREN COMPARED WITH ADULTS, & ADULT VALUES WERE NOT OBTAINED UNTIL ABOUT THIRD YR OF LIFE. RELATIVE DISTRIBUTION VOL, HOWEVER, WERE SIMILAR IN BOTH AGE GROUPS.|IN RATS & MICE ORAL DOSES ARE RAPIDLY ABSORBED WITH PEAK BLOOD CONCN ABOUT 1 HR LATER. ...ELIMINATION IS VIA KIDNEYS, PEAKING @ ABOUT 6TH HR. 80% OF ADMIN DOSE IS ELIMINATED IN 1ST 8 HR. IN DOGS HIGHLY EFFECTIVE CONCN APPEAR IN URINE WITHIN 2-3 HR AFTER ORAL ADMIN.|ABSORPTION EFFICIENCY & RATE OF ELIMINATION OF...NALIDIXIC ACID...DECR IN PT WITH SHIGELLOSIS. POOR ABSORPTION WAS GENERALLY OBSERVED IN YOUNGER PT WITH MARKED DIARRHEA BUT THERE WAS NO READY EXPLANATION FOR DELAYED EXCRETION.|Rapidly and almost completely absorbed from the gastrointestinal tract; bioavailability is approximately 96%. Absorption may be delayed if taken with antacids.|For more Absorption, Distribution and Excretion (Complete) data for NALIDIXIC ACID (7 total), please visit the HSDB record page.

Hepatic. 30% of administered dose is metabolized to the active metabolite, hydroxynalidixic acid. Rapid conjugation of parent drug and active metabolite to inactive metabolites. Metabolism may vary widely among individuals. In the urine, hydroxynalidixic acid represents 80 to 85% of the antibacterial activity.|WHEN NALIDIXIC ACID...IS INGESTED BY MAN, IT IS PARTLY EXCRETED AS FREE... /ACID/ BUT MUCH BIGGER PROPORTION IS EXCRETED AS MONOGLUCURONIDE...& CONSIDERABLE FRACTION AS 7-HYDROXYMETHYL METABOLITE...TOGETHER WITH SMALLER AMT OF LATTER IN CONJUGATED FORM. 3,7-DICARBOXYLIC ACID...IS MINOR METABOLITE.|Nalidixic acid is partially metabolized in the liver to hydroxynalidixic acid and the glucuronic acid conjugates of nalidixic acid and hydroxynalidixic acid. The drug is also partially metabolized to the dicarboxylic acid derivative; there is some evidence suggesting that this metabolite is formed in the kidney.

1.1 to 2.5 hours in healthy adult patients, and up to 21 hours in patients with impaired renal function.|APPROX 96% OF ORALLY ADMIN...IS ABSORBED. PLASMA CONCN OF 20-50 UG/ML MAY BE ACHIEVED, BUT ACID IS 93-97% BOUND TO PLASMA PROTEINS. IN BODY SOME... CONVERTED TO ACTIVE HYDROXYNALIDIXIC ACID, & BOTH ARE EXCRETED INTO URINE. MOST...IS CONJUGATED IN LIVER. PLASMA T/2 IS...8 HR...MAY BE...21 HR IN...RENAL FAILURE.

Evidence exists for Nalidixic acid that its active metabolite, hydroxynalidixic acid, binds strongly, but reversibly, to DNA, interfering with synthesis of RNA and, consequently, with protein synthesis.|IT APPEARS TO ACT BY INHIBITING DNA SYNTH.

SYMPTOMS: Ingestion of this material may cause nausea, vomiting, abdominal pain, allergic reactions and possible liver damage. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. OTHER: Since this chemical is a known or suspected carcinogen you should contact a physician for advice regarding the possible long term health effects and potential recommendation for medical monitoring. Recommendations from the physician will depend upon the specific compound, its chemical, physical and toxicity properties, the exposure level, length of exposure, and the route of exposure. (NTP, 1992)

Recommended treatment consists of the following: To decrease absorption - Performing gastric lavage if overdose is noted early. Specific treatment - Administering anticonvulsants if needed for seizures. Supportive care - Administering fluids and supportive measures such as oxygen and artificial respiration if absorption has occurred. Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.

Acute toxicity from nalidixic acid may be manifested by toxic psychoses, convulsions, increased intracranial pressure, or metabolic acidosis. Vomiting, nausea, and lethargy may also occur. Because of the rapid excretion of nalidixic acid, such reactions are usually short-lived, persisting only 2-3 hours.|Human systemic effects: convulsions, hyperglycemia, sweating, and blood changes in children.

Acid, Nalidixic

20 mg/kg/day /Japanese aquaculture/

NALIDIXIC ACID, NF (NEGGRAM), IS AVAIL AS NALIDIXIC ACID TABLETS, NF, CONTAINING 250 OR 500 MG OF DRUG.

AOAC 970.84. Nalidixic Acid Residues in Animal Tissues. Spectrofluormetric Method. Applicable to chicken liver and muscle contg >/= 100 ppb nalidixic acid.

HIGH PRESSURE LIQUID CHROMATOGRAPHIC METHOD WAS DEVELOPED FOR ASSAY OF NALIDIXIC ACID (NEGGRAM) & HYDROXYNALIDIXIC ACID IN HUMAN PLASMA & URINE. LOWER LIMITS OF DETECTION FOR EACH WERE 0.25 MCG/ML OF EACH IN PLASMA & 2.5 MCG/ML OF EACH IN URINE.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals -> Animal Drugs -> Approved in Taiwan