Pharmacokinetics of single doses of cefoperazone given by the intravenous and intramuscular routes to unweaned calves

Cefoperazone pharmacokinetics were studied in unweaned calves. The antibiotic was administered to 10 calves intravenously, to eight calves intramuscularly at 20 mg kg−1and to 10 calves intramuscularly at 20 mg kg−1together with probenecid at 40 mg kg−1. Serum concentration versus time data were analysed by non-compartmental methods based on the statistical moment theory. The intravenous data were also fitted by a linear, open two-compartment model. The terminal halflife of cefoperazone was 127·9 ± 28·2 min (mean ± sd) after intravenous and 136·9 ± 19·6 min after intramuscular administration. The t½was increased to 257·3 ± 127·3 min by the co-administration of probenecid. The total body clearance was 8·16 ± 1·60 ml min−1kg−1and the volume of distribution at steady state was 0·713 ± 0·167 litre kg−1. The mean residence time values were 87·2 ± 10·6 min after intravenous and 140·3 ± 20·6 min after intramuscular injection and were increased to 264·5 ± 99·8 min by the co-administration of probenecid. The estimated mean absorption time was 53·1 min and the estimated bioavailability after intramuscular administration was 76·3 per cent. The minimal inhibitory concentration (mic90) values of cefoperazone ranged from 0·5 to 2 μg ml−1for Escherichia coli, salmonella groups C, D and E and Pasteurella multocidaisolates. Salmonella group B strains appeared to be highly resistant to cefoperazone with mic90>32 μg ml−1. There were no significant differences between the pharmacokinetic variables calculated by statistical moment theory or compartmental analysis indicating central compartment output of cefoperazone. Statistical moment theory provided an additional independent parameter, the system moment mean residence time for characterisation of drug disposition kinetics.