Interstitial fluid concentrations of cefoxitin, cephazolin and cefamandole

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Abstract
Total and free (protein-unbound) concentrations of cefoxitin, cefamandole and cephazolin were measured over 4 h in the interstitial fluid (IF) of rats and compared to simultaneous blood concentrations following the intramuscular injection of 50 mg/kg doses. Blood, total and free IF concentrations of cefoxitin and cephazolin were higher than those of cefamandole. The free IF/blood concentration ratio of cefoxitin was significantly greater than those of cefamandole and cephazolin (0.77, 0.53, 0.54 respectively derived from area under the curve data; 0.27, 0.11, 0.14, respectively derived from peak concentrations). Binding to rat serum protein (37.5, 42, 78% respectively) was not the major determinant of IF free drug concentrations. The free concentrations of cefoxitin achieved in interstitial fluid suggest that the drug should be useful in the therapy of tissue infections caused by susceptible micro-organisms.