Pharmacokinetics and pharmacodynamics of total and unbound cefoxitin and cefotetan in healthy volunteers.
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.
Carver
P L
PL
University of Michigan, College of Pharmacy, Ann Arbor.
Nightingale
C H
CH
Quintiliani
R
R
D000328:Adult; D001419:Bacteria / Q000187:drug effects; D015313:Cefotetan / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D002440:Cefoxitin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D011485:Protein Binding / Q000187:drug effects
D015313:Cefotetan; D002440:Cefoxitin