Pharmacokinetics and pharmacodynamics of total and unbound cefoxitin and cefotetan in healthy volunteers

J Antimicrob Chemother. 1989 Jan;23(1):99-106. doi: 10.1093/jac/23.1.99.


Cefotetan is a semisynthetic cephalosporin with a broad spectrum of Gram-negative and anaerobic activity. We compared the pharmacokinetics and serum inhibitory activity of 2 g doses of cefotetan and cefoxitin in six healthy volunteers. The half-life of cefotetan (176 min) was significantly longer than that of cefoxitin (49 min). Despite higher protein binding (85% versus 50%), free cefotetan serum concentrations 12 h post dose (1.6 mg/l) were higher than free cefoxitin serum concentrations 6 h post dose (0.32 mg/l). Total and free serum inhibitory titres for Escherichia coli were greater than 1:8 for 12 h post dose for cefotetan, but only 1 h post dose for cefoxitin. Against Bacteroides fragilis, neither cefoxitin nor cefotetan exhibited free serum inhibitory titres greater than 1:8 at the end of their respective dosing intervals. However, cefotetan titres were equivalent or superior to those of cefoxitin over the entire 6 or 12 h dosing interval. Despite relatively high protein binding, cefotetan demonstrates comparable or superior activity 12 h after dosing to cefoxitin 6 h after dosing. More studies comparing the clinical outcome of cefoxitin and cefotetan are needed but our results support the clinical recommendations that cefoxitin should be given every 6 h, and cefotetan every 12 h.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Bacteria / drug effects
  • Cefotetan / administration & dosage
  • Cefotetan / pharmacokinetics*
  • Cefotetan / pharmacology
  • Cefoxitin / administration & dosage
  • Cefoxitin / pharmacokinetics*
  • Cefoxitin / pharmacology
  • Female
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Protein Binding / drug effects


  • Cefotetan
  • Cefoxitin