クラブラン酸 化学特性,用途語,生産方法
解説
クラブラン酸．Streptomyces clavuligerusが産生するβ-ラクタマーゼ阻害剤で，弱い抗菌力もある．オキサペナム骨格をもつ物質として最初に発見された．不安定な油状物質．β-ラクタマーゼを産生する耐性菌の感受性を高める．β-ラクタム系抗生物質アモキシシリンまたはチカルシリンとの合剤で使用される．Na塩はLD50 4 g/kg(マウス，静注)．
用途
クラブラン酸 (Clavulanic acid) は、1974年に放線菌の代謝産物から発見された物質。最初に臨床使用されたβ-ラクタマーゼ阻害剤である。
単独では抗菌力が弱いが、β-ラクタム系抗生物質を不活化する酵素であるβ-ラクタマーゼを不可逆的に阻害する作用があることから、ペニシリンとの合剤として臨床応用されている。
効能
抗生物質, 細胞壁合成阻害薬, ベータラクタマーゼ阻害薬
説明
Clavulanic acid is a mold product with only weak intrinsic antibacterial activity, but it is an excellent
irreversible inhibitor of most β-lactamases. It is believed to acylate the active site serine by mimicking the
normal substrate. Hydrolysis occurs with some β-lactamases, but in many cases, subsequent reactions occur
that inhibit the enzyme irreversibly. This leads to its classification as a mechanism-based inhibitor (or
so-called suicide substrate). The precise chemistry is not well understood, but when clavulanic
acid is added to ampicillin and amoxicillin preparations, the potency against β-lactamase–producing strains
is markedly enhanced.
使用
beta-lactamase inhibitor
定義
ChEBI: Antibiotic isolated from Streptomyces clavuligerus. It acts as a suicide inhibitor of bacterial beta-lactamase enzymes.
作用機序
β‐ラクタム抗生物質は，細菌の細胞壁の合成を阻害して菌を殺すので，細胞壁をもたないヒトなどの細胞には作用せず，したがって毒性はきわめて少なく，すぐれた治療薬である。
世界保健機関（WHO）
The amoxicillin/clavulanic acid combination should be reserved
for infections likely or known to be caused by amoxicillin- resistant beta-lactamase
producing strains. Amoxicillin/clavulanic acid is listed in the WHO Model List of
Essential Drugs.
抗菌性
It exhibits broad-spectrum but low intrinsic activity, most
MICs being in the range 16–128 mg/L. Enterobacteriaceae
and Staph. aureus are among the more sensitive and Ps. aeruginosa
the most resistant organisms. MICs of 8 mg/L against
H. influenzae and 0.1–4 mg/L for penicillinase-producing
N. gonorrhoeae are notable.
一般的な説明
Clavulanic acid was found in the culture broth of Streptomyces clavuligerus by Beecham Research Laboratories in 1976. It was the first β-lactamase inhibitor. This antibiotic shows weak antibacterial activity against grampositive and gram-negative organisms but strong inhibitory activity against the β-lactamase produced by ampicillin-resistant bacteria. Clavulanic acid is used orally in combination with amoxicillin and with ticarcillin by injection to enhance the activities of these antibiotics against resistant infections.
薬物動態学
It exhibits broad-spectrum but low intrinsic activity, most
MICs being in the range 16–128 mg/L. Enterobacteriaceae
and Staph. aureus are among the more sensitive and Ps. aeruginosa
the most resistant organisms. MICs of 8 mg/L against
H. influenzae and 0.1–4 mg/L for penicillinase-producing
N. gonorrhoeae are notable.
臨床応用
Clavulanic acid is an antibiotic isolated from Streptomycesclavuligeris. Structurally, it is a 1-oxopenam lacking the6-acylamino side chain of penicillins but possessing a 2-hydroxyethylidene moiety at C-2. Clavulanic acid exhibitsvery weak antibacterial activity, comparable with that of6-APA and, therefore, is not useful as an antibiotic. Itis, however, a potent inhibitor of S. aureus β-lactamaseand plasmid-mediated β-lactamases elaborated by Gramnegativebacilli.
Combinations of amoxicillin and the potassium saltof clavulanic acid are available (Augmentin) in variousfixed-dose oral dosage forms intended for the treatment ofskin, respiratory, ear, and urinary tract infections causedby -lactamase–producing bacterial strains. These combinationsare effective against β-lactamase–producingstrains of S. aureus, E. coli, K. pneumoniae, Enterobacter,H. influenzae, Moraxella catarrhalis, and Haemophilusducreyi, which are resistant to amoxicillin alone. The oral bioavailability of amoxicillin and potassium clavulanate issimilar. Clavulanic acid is acid-stable. It cannot undergo penicillanicacid formation because it lacks an amide side chain.Potassium clavulanate and the extended-spectrum penicillinticarcillin have been combined in a fixed-dose, injectableform for the control of serious infections caused byβ-lactamase–producing bacterial strains. This combinationhas been recommended for septicemia, lower respiratory tractinfections, and urinary tract infections caused by β-lactamase–producing Klebsiella spp., E. coli, P. aeruginosa,and other Pseudomonas spp., Citrobacter spp., Enterobacterspp., S. marcescens, and S. aureus. It also is used in bone andjoint infections caused by these organisms. The combinationcontains 3 g of ticarcillin disodium and 100 mg of potassiumclavulanate in a sterile powder for injection (Timentin).
クラブラン酸 上流と下流の製品情報
原材料
準備製品