1-Ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridin-3-carbons?ure Chemische Eigenschaften,Einsatz,Produktion Methoden
R-S?tze Betriebsanweisung:
R63:Kann das Kind im Mutterleib m?glicherweise sch?digen.
R42/43:Sensibilisierung durch Einatmen und Hautkontakt m?glich.
R40:Verdacht auf krebserzeugende Wirkung.
R20/21/22:Gesundheitssch?dlich beim Einatmen,Verschlucken und Berührung mit der Haut.
S-S?tze Betriebsanweisung:
S22:Staub nicht einatmen.
S36/37:Bei der Arbeit geeignete Schutzhandschuhe und Schutzkleidung tragen.
S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn m?glich, dieses Etikett vorzeigen).
S24:Berührung mit der Haut vermeiden.
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
Chemische Eigenschaften
Nalidixic acid is a pale yellow crystalline powder. It is soluble in chloroform, slightly soluble in alcohol and strong alkaline solutions, and practically insoluble in water and ether.
History
Nalidixic acid was the first quinolone drug in human history and is also regarded as the progenitor of the quinolone family. Initially used primarily to treat urinary tract infections, it ushered in a new era of synthetically produced antibacterial drugs and led to the development of various subsequent quinolone antibacterial agents.
Verwenden
Nalidixic acid(NegGram) is a synthetic 1,8-naphthyridine antimicrobial agent with a limited bacteriocidal spectrum. It is an inhibitor of the A subunit of bacterial DNA gyrase. Evidence exists that the active metabolite, hydroxynalidixic acid, binds stron
Definition
ChEBI: Nalidixic acid is a monocarboxylic acid comprising 1,8-naphthyridin-4-one substituted by carboxylic acid, ethyl and methyl groups at positions 3, 1, and 7, respectively. An orally administered antibacterial, it is used in the treatment of lower urinary-tract infections due to Gram-negative bacteria, including the majority of E. coli, Enterobacter, Klebsiella, and Proteus species. It has a role as an antimicrobial agent, an antibacterial drug and a DNA synthesis inhibitor. It is a monocarboxylic acid, a 1,8-naphthyridine derivative and a quinolone antibiotic. It is a conjugate acid of a nalidixic acid anion.
Antimicrobial activity
It displays good activity in vitro against a wide range of Enterobacteriaceae.
Allgemeine Beschreibung
Cream-colored powder.
Air & Water Reaktionen
Insoluble in water.
Health Hazard
SYMPTOMS: Ingestion of Nalidixic acid may cause nausea, vomiting, abdominal pain, allergic reactions and possible liver damage.
Brandgefahr
Flash point data for Nalidixic acid are not available, but Nalidixic acid is probably combustible.
Pharmazeutische Anwendungen
A 1,8 naphthyridone derivative available for oral administration.
Pharmakokinetik
Oral absorption: >90%
Cmax 1 g oral: c. 25 mg/L
Plasma half-life:c.1.5h
Volume of distribution :0.4 L/kg
Plasma protein binding: 93%
The plasma concentrations achieved after oral administration vary widely. In infants with acute shigellosis, absorption is much impaired by diarrhea. Administration with an alkaline compound leads to higher plasma concentrations, partly as the result of enhanced solubility (nalidixic acid is much more soluble at higher pH) and absorption and partly because of reduced tubular reabsorption.
It is rapidly metabolized, principally to the hydroxy acid, which is bacteriologically active, and glucuronide conjugates, which are not. The entire administered dose appears in the urine over a 24 h period. Elimination is reduced by probenecid. In the presence of renal impairment there is little accumulation of the active compound because it continues to be metabolized. However, elimination of metabolites is progressively delayed as renal function declines. About 4% of a dose appears in the feces.
Clinical Use
1-Ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid (NegGram) occurs as a pale buff crystalline powder that is sparingly soluble in water and ether but solublein most polar organic solvents.Nalidixic acid is useful in the treatment of urinary tractinfections in which Gram-negative bacteria predominate.The activity against indole-positive Proteus spp. is particularlynoteworthy, and nalidixic acid and its congeners representimportant alternatives for the treatment of urinary tractinfections caused by strains of these bacteria resistant toother agents. Nalidixic acid is rapidly absorbed, extensivelymetabolized, and rapidly excreted after oral administration.The 7-hydroxymethyl metabolite is significantly more activethan the parent compound. Further metabolism of theactive metabolite to inactive glucuronide and 7-carboxylicacid metabolites also occurs. Nalidixic acid possesses at1/2elim of 6 to 7 hours. It is eliminated, in part, unchanged inthe urine and 80% as metabolites.
Nebenwirkungen
Adverse reactions are generally those common to all quinolones: gastrointestinal tract and CNS disturbances and skin rashes, including eruptions related to photosensitivity. About half of the reported CNS reactions involve visual disturbances, hallucinations or disordered sensory perception. Severe excitatory states, including acute psychoses and convulsions, are usually observed in patients receiving high dosages. The drug should be avoided in patients with psychiatric disorders or epilepsy.
Acute intracranial hypertension has been observed in children, some of whom have also manifested cranial nerve palsies. Hemorrhage has occurred in patients who were also receiving warfarin, presumably due to displacement of the anticoagulant from its protein binding sites by the nalidixic acid. Hemolytic anemia has been described several times in infants with or without glucose-6-phosphate dehydrogenase deficiency; in adults, death has occurred from autoimmune hemolytic anemia. Arthralgia and severe metabolic acidosis have rarely been reported.
Sicherheitsprofil
Poison by intravenous
and intraperitoneal routes. Moderately toxic
by ingestion and subcutaneous routes. An
experimental teratogen. Human systemic
effects: convulsions, hyperglycemia,
sweating, and blood changes in children.
Experimental reproductive effects.Questionable carcinogen with experimental
carcinogenic and tumorigenic data. Human
mutation data reported. Used as an
antibacterial agent and urinary tract
antiseptic. When heated to decomposition it
emits toxic fumes of NOx.
l?uterung methode
Nalidixic acid crystallises from H2O or EtOH as a pale buff powder. It is soluble at 23o in CHCl3 (3.5%), toluene (0.16%), MeOH (0.13%), EtOH (0.09%), H2O (0.01%) and Et2O (0.01%). It inhibits nucleic acid and protein synthesis in yeast. [Lesher et al. J Med & Pharm Chem 5 1063 1962.]
1-Ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridin-3-carbons?ure Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
