[Show abstract][Hide abstract] ABSTRACT: In an attempt to explain the discrepancy between the weak in vitro activity and good clinical efficacy of ciclacillin, a time-dosage-efficacy study was made in order to investigate the relationship of the effectiveness of this antibiotic to the interval between experimental infection and administration in comparison to ampicillin, which because of its similar antimicrobial spectrum and completely different pharmacokinetic properties was particularly suitable for use in the study. Various single oral doses of both antibiotics were administered once to NMRI (SPF) mice at various intervals (0, 1, 2 or 3 h) following experimental infection with E. coli WT 102, E. coli 3033 or E. coli 026:B6 and the CD50's determined and compared statistically. It was demonstrated that the chemotherapeutic effectiveness of both antibiotics was markedly dependent on the interval between experimental infection and administration. Whereas ampicillin was superior to ciclacillin when drug and infective organism were administered simultaneously (0 h), ciclacillin was superior to ampicillin when it was administered 3 h after experimental infection. Both antibiotics were about equally effective when administered 1 or 2 h after infection. The difference in the serum concentrations and rates of absorption and excretion of the two drugs is assumed to be the reason for this phenomenon, and the pharmacokinetic characteristics of ciclacillin, in particular its rapid and almost complete absorption and rapid attainment of high peak serum levels, are discussed as at least a partial explanation of the difference in its in vitro and in vivo activities.
No preview · Article · Oct 1975 · Arzneimittel-Forschung