イミペネム/シラスタチン 化学特性,用途語,生産方法
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Imipenem is N-formimidoylthienamycin, the most successfulof a series of chemically stable derivatives of thienamycinin which the primary amino group is converted to a nonnucleophilicbasic function. Cilastatin is an inhibitor of DHPI.The combination (Primaxin) provides a chemically and enzymaticallystable form of thienamycin that has clinicallyuseful pharmacokinetic properties. The half-life of the drugis nonetheless short (t1/2 ～1 hour) because of renal tubularsecretion of imipenem. Imipenem retains the extraordinarybroad-spectrum antibacterial properties of thienamycin. Itsbactericidal activity results from the inhibition of cell wallsynthesis associated with bonding to PBPs 1b and 2.Imipenem is very stable to most β-lactamases. It is an inhibitorof β-lactamases from certain Gram-negative bacteriaresistant to other β-lactam antibiotics (e.g., P. aeruginosa, S.marcescens, and Enterobacter spp.).
Imipenem is indicated for the treatment of a wide variety ofbacterial infections of the skin and tissues, lower respiratorytract, bones and joints, and genitourinary tract, as well as ofsepticemia and endocarditis caused by β-lactamase–producingstrains of susceptible bacteria. These include aerobic Grampositiveorganisms such as S. aureus, Staphylococcus epidermidis,enterococci, and viridans streptococci; aerobic Gramnegativebacteria such as E. coli, Klebsiella, Serratia,Providencia, Haemophilus, Citrobacter, and indole-positiveProteus spp., Morganella morganii, Acinetobacter andEnterobacter spp., and P. aeruginosa and anaerobes such as B.fragilis and Clostridium, Peptococcus, Peptidostreptococcus,Eubacterium, and Fusobacterium spp. Some Pseudomonasspp. are resistant, such as P. maltophilia and P. cepacia, as aresome methicillin-resistant staphylococci. Imipenem is effectiveagainst non–β-lactamase-producing strains of these andadditional bacterial species, but other less expensive andequally effective antibiotics are preferred for the treatment ofinfections caused by these organisms.
The imipenem–cilastatin combination is marketed as asterile powder intended for the preparation of solutions for intravenousinfusion. Such solutions are stable for 4 hours at25°C and up to 24 hours when refrigerated. The concomitantadministration of imipenem and an aminoglycoside antibioticresults in synergistic antibacterial activity in vivo. The twotypes of antibiotics are, however, chemically incompatibleand should never be combined in the same intravenous bottle.
イミペネム/シラスタチン 上流と下流の製品情報
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