ラモプラニン 化学特性,用途語,生産方法
説明
Ramoplanin (A 16686, A16686A, MDL 62198) is a novel oral nonabsorbable 17-amino-acid cyclic lipoglycodepsipeptide antibiotic from Biosearch Italy. Ramoplanin is an antibiotic complex, first identified in 1984, that was isolated from the fermentation broth of Actinoplanes sp. ATCC 33076. It is a mixture of three closely related compounds, ramoplanin A1–A3, which differ only in the acyl group attached to the Asn-1 N-terminus; ramoplanin A2 is the most abundant.
使用
Ramoplanin is a potent cyclic lipoglycodepsipeptide antibiotic that exhibits wide spectrum of antibiotic properties against gram-positive and gram-negative bacteria.
抗菌性
Ramoplanin displays activity against aerobic and anaerobic Grampositive bacteria by preventing cell wall peptidoglycan formation through binding to a key intermediate moiety, lipid II, and thereby disrupting bacterial cell wall synthesis. The primary use of ramoplanin is in the treatment of Clostridium difficile infections.
作用機序
The mechanism of action of ramoplanin involves sequestration of peptidoglycan biosynthesis lipid intermediates, thus physically occluding these substrates from proper utilization by the latestage peptidoglycan biosynthesis enzymes MurG and the transglycosylases (TGases). Ramoplanin is structurally related to two cell wall-active lipodepsipeptide antibiotics, janiemycin and enduracidin, and is functionally related to members of the lantibiotic class of antimicrobial peptides (mersacidin, actagardine, nisin, and epidermin) and glycopeptide antibiotics. As a consequence of its unique mechanism of action, cross-resistance with existing glycopeptides and beta-lactam antibiotics has not been observed.
薬物動態学
Ramoplanin is not absorbed from the intestinal tract. When
ramoplanin (200 and 400 mg) was administered orally to two groups
of healthy volunteers over a period of 10 days, no ramoplanin could be
detected in plasma and urine. With the 200-mg dose, concentrations
in stools varied between 467 and 1043 mg/g, and with the 400-mg dose,
concentrations were between 765 and 2032 mg/g.
Results from an in vitro gut model and hamster model revealed that
ramoplanin may be more effective than vancomycin at killing spores
and preventing spore recrudescence.
毒性学
When administered orally in a double-blind randomized placebocontrolled study, no adverse reactions were observed in patients receiving two daily doses of ramoplanin (100 or 400 mg) in comparison with the placebo. Single and repeated topical application in ten healthy human volunteers revealed very low irritation rates and no sensitization after 21 days.
ラモプラニン 上流と下流の製品情報
原材料
準備製品