Journal Article

Changes in fecal flora and comparative multiple‐dose pharmacokinetics of ceftibuten, cefpodoxime proxetil and amoxycillin/clavulanate

Reidenberg, Bruce E., Nord, Carl Erik, Lode, Hartmut, Bristol, David, Hamacher, Jürg, Koeppe, Peter, Luepke, Jörg, Borner, Klaus

1999

Overview

Objective: To investigate changes in fecal flora and multiple‐dose pharmacokinetics with the oral antibiotics ceftibuten 400 mg daily and cefpodoxime proxetil (CPX) 200 mg every 12 h, compared to amoxycillin/clavulanate 500/125 mg every 8 h during and following 1 week of medication. Methods: In an open randomized triple crossover design, 18 (nine female, nine male) healthy volunteers received each drug for 7 days, followed by a ‘washout’ period of 4 weeks. Serum and urine levels of the substances were determined by bioassay, and for ceftibuten isomers by high‐pressure liquid chromatography. Statistical analysis of quantitative aerobic and anaerobic cultures of feces was performed, and β‐lactamase activity was determined. Results: Ceftibuten showed a mean Cmax of 18.9 (SD 3.0) mg/L, a terminal half‐life of 2.89 h, and an AUCtot of 100 (21.8) mg.h/L; protein binding was 63.7 (5.1)%, and accumulation was marginal. Cefpodoxime proxetil had a Cmax of 1.92 (0.61) mg/L, a terminal half‐life of 1.97 (0.42) h and an AUCtot of 10.8 (3.3) mg.h/L; no accumulation was seen. Amoxycillin and clavulanate had Cmax values of 7.15 (2.16) mg/L and 3.39 (1.31) mg/L, terminal half‐life values of 1.03 (0.15) h and 0.93 (0.17) h, AUCtot values of 20.0 (4.2) mg.h/L and 8.87 (3.10) mg.h/L, and there was no accumulation. Statistical analysis for ech microorganism in fecal samples showed significant differences between amoxycillin/clavulanate and the two third‐generation cephalosporins, but virtually no differences between ceftibuten and cefpodoxime proxetil. Eleven of 12 volunteers reported loose stools (days 2–7, mean duration 4.4 (SD 2.7) days) with amoxycillin/clavulanate, but nobody during ceftibuten administration and one volunteer during cefpodoxime proxetil administration. Conclusions: Ceftibuten showed excellent and cefpodoxime favorable pharmacokinetic properties, with significantly less pronounced fecal flora changes and intestinal side effects compared to amoxycillin/clavulanate. The multiple crossover design allows powerful microbiological statistical analysis and pharmacokinetic parameter comparisons.

• Publisher: Blackwell Publishing Ltd,Blackwell,Elsevier Limited
• Subject: amoxycillin/clavulanate / Antibacterial agents / Antibiotics. Antiinfectious agents. Antiparasitic agents / Biological and medical sciences / cefpodoxime proxetil / Ceftibuten / fecal flora / Flora / Medical sciences / Pharmacokinetics / Pharmacology. Drug treatments / statistical analysis / triple crossover design / β‐lactamase activity