セフォタキシム 化學(xué)特性,用途語,生産方法
解説
セフォタキシムは，セフェム系抗生物質(zhì)の一つ。敗血癥や創(chuàng)傷?熱傷および手術(shù)後の二次感染などに効能をもつ。
効能
抗生物質(zhì), 細(xì)胞壁合成阻害薬
説明
Like other third-generation
cephalosporins, it has excellent anti-Gram-negative activity and is useful institutionally. It has a
metabolically vulnerable acetoxy group attached to C-3 and loses approximately 90% of its activity when this
is hydrolyzed. This metabolic feature also complicates the pharmacokinetic data, because both active forms
are present and have different properties. Cefotaxime should be protected from heat and light and may color
slightly without significant loss of potency. Like other third-generation cephalosporins, cefotaxime has less
activity against staphylococci but has greater activity against Gram-negative organisms.
使用
Cefotaxime has a broad spectrum of antibicrobial use. It acts bactericidally. It is highly
active with respect to Gram-negative microorganisms (E. coli, Citrobacter, Proteus
mirabilis, P. indole, Providencia, Klebsiella, Serratia), and a few strains of Pseudomonas,
H. influenzae that are resistant to other antibiotics. Cefotaxime is less active with respect
to streptococci, pneumococci, meningococci, gonococci, and bacteroides. It is resistant to
the majority of beta-lacatamases of Gram-positive and Gram-negative microorganisms.
This drug is used for severe bacterial infections caused by microorganisms that are sensitive to the drug such as peritonitis, sepsis, abdominal infections, infections of the pelvis
minor, infections of the lower respiratory tract, urinary tract, bones, joints, skin, soft tissues,
and infected wounds and burns. Synonyms of this drug are claforan, zarivis, and others.
抗菌性
The aminothiazoyl and methoximino groups at the 7-amino
position confer, respectively, potent activity against many
Gram-negative rods and cocci and stability to
most β-lactamases. Ps. aeruginosa, Sten. maltophilia and other
pseudomonads are often resistant. Brucella melitensis and some
strains of Nocardia asteroides are susceptible. Activity against
L. monocytogenes and B. fragilis is poor.
獲得抵抗性
Many enterobacteria resistant to other b-lactam agents are
susceptible, but selection of resistant strains with derepressed
chromosomal molecular class C cephalosporinases may occur. Gram-negative bacilli producing variants
of the TEM enzymes (pp. 230–231) are resistant.
薬物動(dòng)態(tài)學(xué)
C
max 500 mg intramuscular: 10–15 mg/L after 0.5–1 h
1 g intravenous (15-min infusion): 90 mg/L end infusion
Plasma half-life: c.1 h
Volume of distribution: 32–37 L
Plasma protein binding: c. 40%
Distribution
It is widely distributed, achieving therapeutic concentrations
in sputum, lung tissue, pleural fluid, peritoneal fluid, prostatic
tissue and cortical bone. In patients receiving 2 g every
8 h, mean CSF concentrations in aseptic meningitis were 0.8 mg/L. Levels of 2–15 mg/L can be found in the CSF
in the presence of inflammation after doses of 50 mg/kg by
intravenous infusion over 30 min. A single intraventricular
dose of 40 mg/kg produced levels at 2, 4 and 6 h of 6.4, 5.7
and 4.5 mg/L, respectively.
Metabolism
About 15–25% of a dose is metabolized by hepatic esterases to
the desacetyl form, which may have some clinical importance
because of its concentration in bile and accumulation in renal
failure. Desacetylcefotaxime has about 10% of the activity of
the parent against enterobacteria, less against Staph. aureus.
Its half-life in normal subjects is around 1.5 h.
Excretion
Elimination is predominantly by the renal route, more than
half the dose being recovered in the urine over the first 24 h,
about 25% as the desacetyl derivative. Excretion is depressed
by probenecid and declines in renal failure with accumulation
of the metabolite. In patients with creatinine clearances in the
range 3–10 mL/min, the plasma half-life rose to 2.6 h while
that of the metabolite rose to 10 h.
臨床応用
Cefotaxime is widely used in neutropenic patients, respiratory
infection, meningitis, intra-abdominal sepsis, osteomyelitis,
typhoid fever, urinary tract infection, neonatal sepsis and
gonorrhea.
副作用
Minor hematological and dermatological side effects common
to group 4 cephalosporins have been described.
Superinfection with Ps. aeruginosa in the course of treatment
has occurred. Occasional cases of pseudomembranous colitis
have been reported.
セフォタキシム 上流と下流の製品情報(bào)
原材料
準(zhǔn)備製品