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Antimicrob Agents Chemother. 1992 December; 36(12): 2825-2834

Antibacterial properties of Ro 40-6890, a broad-spectrum cephalosporin, and its novel orally absorbable ester, Ro 41-3399.

P Angehrn, P Hohl, C Hubschwerlen, M Page and R Then

Preclinical Research, F. Hoffmann-La Roche Ltd., Basel, Switzerland.

ABSTRACT

Ro 41-3399 is a novel orally active ester of Ro 40-6890, an aminothiazolyl cephalosporin with potent in vitro activities against commonly encountered aerobic gram-positive bacteria (streptococci and methicillin-susceptible staphylococci) and gram-negative bacteria (members of the family Enterobacteriaceae, haemophili, meningococci, and gonococci). In terms of the MICs determined by the methods recommended by the National Committee for Clinical Laboratory Standards, for 50 and 90% of gram-positive organisms, the water-soluble free carboxylic acid Ro 40-6890 proved to be at least as active as or two- to fourfold more active than cefpodoxime, cefuroxime, cefaclor, amoxicillin, amoxicillin-clavulanic acid, and ceftriaxone; against aerobic gram-negative organisms, Ro 40-6890 was usually two- to fourfold more active than cefpodoxime, the next most potent of the oral drugs under comparison, but remained usually two- to fourfold weaker than ceftriaxone. Ro 40-6890 showed a high affinity for the essential penicillin-binding proteins of susceptible bacteria and was resistant to hydrolysis by a broad array of beta-lactamases. Ro 41-3399 bopentil was well absorbed in mice when administered by oral gavage and proved effective in several experimental bacterial infections. Further studies with Ro 41-3399 and Ro 40-6890 are in progress.

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Antimicrob Agents Chemother. 1992 December; 36(12): 2825-2834

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