Pharmacodynamics and pharmacokinetics of cefoperazone and cefamandole in dogs following single dose intravenous and intramuscular administration

The pharmacokinetics and intramuscular (i.m.) bioavailability of cefoperazone and cefamandole (20mg/kg) were investigated in dogs and the findings related to minimal inhibitory concentrations (MICs) for 90 bacterial strains isolated clinically from dogs. The MICs of cefamandole for Staphylococcus intermedius (MIC(90) 0.125 microg/mL) were lower than those of cefoperazone (MIC(90) 0.5 micro/mL) although the latter was more effective against Escherichia coli strains (MIC(90) 2.0 microg/mL vs. 4.0 microg/mL). The pharmacokinetics of the drugs after intravenous administrations were similar: a rapid distribution phase was followed by a slower elimination phase (t((1/2)lambda2) 84.0+/-21.3 min for cefoperazone and 81.4+/-9.7 min for cefamandole). The apparent volume of distribution and body clearance were 0.233 L/kg and 1.96 mL/kg/min for cefoperazone, 0.190 L/kg and 1.76 mL/kg/min for cefamandole. After i.m. administration the bioavailability and peak serum concentration of cefamandole (85.1+/-13.5% and 35.9+/-5.4 microg/mL) were significantly higher than cefoperazone (41.4+/-7.1% and 24.5+/-3.0 micog/mL), but not the serum half-lives (t(1/2el) 134.3+/-12.6 min for cefoperazone and 145.4+/-12.3 min for cefamandole). The time above MIC(90) indicated that cefamandole can be administered once daily to dogs for the treatment of staphylococcal infections (T>MIC for S. intermedius 23.8+/-0.3 and for Staphylococcus aureus 21.6+/-0.6h).