[A new oral cephem, cefdinir: its structure-activity relationships and biological profile].
This article reviews structure-activity relationships and biological properties of a new oral cephem, cefidinir (CFDN). It also describes a hypothesis concerning the absorption mechanism from the intestine. Antibacterial activities and the oral absorption efficiencies were studied with regard to 3-vinyl cephalosporins with various 7-acyl side chains. From the study, 2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetyl group was selected and various 3-substituents were screened. As a result, it was found that the vinyl compound, CFDN, showed excellent antibacterial activity and good oral absorption in rats. In vitro and in vivo antibacterial activities, the affinity for PBPs and the stability to beta-lactamases revealed that CFDN had well balanced antimicrobial activities against Gram-positive and Gram-negative bacteria and good biological properties. The pharmacokinetics of CFDN in healthy volunteers showed that serum concentration and half life were good enough to make CFDN an effective therapeutic agent. The mechanism of intestinal absorption of CFDN and related oral cephems are discussed and a hypothesis for molecular recognition by the carrier protein in the intestine is proposed.
Sakane
K
K
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
Inamoto
Y
Y
Takaya
T
T
D000818:Animals; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy; D000077525:Cefdinir; D002511:Cephalosporins / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D006801:Humans; D007408:Intestinal Absorption; D013329:Structure-Activity Relationship
D002511:Cephalosporins; D000077525:Cefdinir