ナリジクス酸 化学特性,用途語,生産方法
外観
白色～わずかにうすい黄色, 結晶性粉末～粉末
溶解性
水酸化ナトリウム溶液溶状：試験適合
解説
ナリジクス酸,淡黄色の結晶．融点229～230 ℃．大腸菌，肺炎桿(かん)菌など，グラム陰性菌に特異的に作用し，ほかの療法剤と交差耐性を示さないので，腸管や尿路感染症に投与する．LD50 1560 mg/kg(マウス，経口)．
森北出版「化学辞典（第2版）
用途
グラム陰性菌に強力な抗菌作
用を示します。DNA ジャイレースを阻害し、
抗菌作用を示します
用途
グラム陰性菌に強力な抗菌作
用を示します。DNA ジャイレースを阻害し、
抗菌作用を示します。
用途
動物用医薬品定量用の標準品。
製造
1,2-ジヒドロ-4-ヒドロキシ-7-メチル-1,8-ナフチリジン-3-カルボン酸をN-エチル化，酸化して合成された抗菌剤ナリジクス酸．
効能
抗菌薬, 核酸合成阻害薬
化学的特性
Crystalline Powder
使用
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
定義
ChEBI: A monocarboxylic acid comprising 1,8-naphthyridin-4-one substituted by carboxylic acid, ethyl and methyl groups at positions 3, 1, and 7, respectively.
抗菌性
It displays good activity in vitro against a wide range of Enterobacteriaceae.
一般的な説明
Cream-colored powder.
空気と水の反応
Insoluble in water.
健康ハザード
SYMPTOMS: Ingestion of Nalidixic acid may cause nausea, vomiting, abdominal pain, allergic reactions and possible liver damage.
火災危険
Flash point data for Nalidixic acid are not available, but Nalidixic acid is probably combustible.
応用例（製薬）
A 1,8 naphthyridone derivative available for oral administration.
薬物動態学
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.
臨床応用
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.
副作用
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.
安全性プロファイル
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.
純化方法
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.]
ナリジクス酸 上流と下流の製品情報
原材料
準備製品