ネチルマイシン 化学特性,用途語,生産方法
効能
抗生物質, タンパク質合成阻害薬
説明
This is a semisynthetic derivative of sisomicin, which was developed by
ethylation of the 1-N position of the deoxystreptamine ring of
sisomicin . Clinically, netilmicin is used as a sulfate. Netilmicin has a similar
in vitro antibacterial spectrum to that of gentamicin but, unlike
sisomicin, it is active against a proportion of gentamicin-resistant
Gram-negative bacilli. However, netilmicin is not
active against as wide a range of gentamicin-resistant Gram-negative
bacilli as amikacin. Nevertheless, it may be occasionally indicated as
an alternative to amikacin for the treatment of infections caused by
gentamicin-resistant but netilmicin-susceptible Gram-negative organisms. The following details apply only to netilmicin
抗菌性
It is active against a wide range of
enterobacteria as well as many Acinetobacter, Pseudomonas,
Citrobacter, Proteus and Serratia spp. Staphylococci, including
methicillin-resistant and coagulase-negative strains, are
usually susceptible. Nocardiae are inhibited by 0.04–1 mg/L.
Providencia spp. and anaerobic bacteria are generally
resistant.
It is active against some gentamicin-resistant strains, particularly
those that synthesize ANT(2″) or AAC(3)-I. It exhibits
typical aminoglycoside properties: bactericidal activity at or
close to the MIC; greater activity at alkaline pH; depression of
activity against Pseudomonas by divalent cations; and synergy
with β-lactam antibiotics. Bactericidal synergy can be demonstrated
regularly with benzylpenicillin against viridans streptococci
and E. faecalis, but seldom against E. faecium, which
characteristically synthesizes AAC(6′), to which netilmicin is
susceptible.
獲得抵抗性
It is resistant to ANT(2), AAC(3)-I and AAC(3)-III, but
sensitive to AAC(6). AAC(3)-II confers
resistance, but generally to a lesser degree than to
gentamicin.
Resistance rates are generally about the same as, or a little
lower than, those for gentamicin.
薬理学
Netilmicin is also highly effective with respect to Gram-negative microorganisms (blue-pus
and colon bacilli, rabbit fever, serratia, providencia, enterobacteria, proteus, salmonella, shigella), as well as a few Gram-positive microorganisms (staphylococci and a few strains
of streptococci).
It is used for severe bacterial infections that are caused by microorganisms sensitive to
the drug. Synonyms of this drug are netillin, zetamycin, and others.
臨床応用
Severe infections (including septicemia, lower respiratory tract infections,
urinary tract infections, peritonitis, endometritis) caused by susceptible
strains of Gram-negative bacilli and staphylococci
副作用
It is considered to be less nephrotoxic than gentamicin, a
difference not easily explained since the renal clearance and
renal and medullary concentrations of the drugs appear to
be similar. Both vestibular and cochlear toxicity appear to be
low and vestibular toxicity without audiometric abnormality
is rare. In some patients, plasma concentrations up to
30 mg/L over periods exceeding 1 week have not resulted in
ototoxicity. Evidence of some renal toxicity in the excretion
of granular casts has occurred fairly frequently in patients receiving 7.5 mg/kg per day, and is more likely to occur
in the elderly and in those receiving higher doses or longer
courses. In patients treated for an average of 35 days
with 2.4–6.9 mg/kg per day, there was no effect on initially
normal renal function, even in the elderly. Long-term treatment
led to an increase in elimination half-life from 1.5 to
1.9 h. Nephrotoxicity has been observed in some diabetic
patients. Overall estimates of the frequency of nephrotoxicity
have ranged from 1% to 18%. Increases in serum
transaminase and alkaline phosphatase concentrations have
been seen in some patients without other evidence of hepatic
impairment.
Once-daily dosing is thought to be safer than twice or three
times daily dosing.
薬物相互作用
Netilmicin is inactivated less than gentamicin and tobramycin by high
concentrations of various penicillins .
At the highest penicillin concentration studied (500 mg/ml), inactivation of netilmicin was a little higher than amikacin. The in vivo
inactivation of netilmicin was compared with gentamicin in patients
with end-stage renal disease. The terminal
elimination half-life for gentamicin decreased from 60 to 25 hours,
whereas the values for netilmicin remained essentially the same at 42
to 40 hours. Such patients receiving combinations of netilmicin and
various penicillins will not require further dose adjustment.
Netilmicin differed from other aminoglycosides by reducing T3 or
triiodothyroxime levels in serum.
ネチルマイシン 上流と下流の製品情報
原材料
N-ACETYL-D-GALACTOSAMINE(GALACTOSE-13C6, 99%)
シアノ水素化ほう素ナトリウム
シソマイシン
硫酸水素
アセトアルデヒド
D-Streptamine, O-2,6-bis(acetylamino)-2,3,4,6-tetradeoxy-α-D-glycero-hex-4-enopyranosyl-(1→4)-O-[3-deoxy-4-C-methyl-3-(methylamino)-β-L-arabinopyranosyl-(1→6)]-N3-acetyl-2-deoxy-N1-ethyl- (9CI)
D-Streptamine, O-2,6-bis(acetylamino)-2,3,4,6-tetradeoxy-α-D-glycero-hex-4-enopyranosyl-(1→4)-O-[3-deoxy-4-C-methyl-3-(methylamino)-β-L-arabinopyranosyl-(1→6)]-N3-acetyl-2-deoxy-
準備製品