Chronokinetics of ceftazidime after intramuscular administration to dogs

摘要

Ceftazidime, a third-generation cephalosporin, is widely used for the treatment of Pseudomonas aeruginosa infections. The aims of the present study were to characterize the pharmacokinetics of ceftazidime and to estimate the T>MIC against P. aeruginosa, after its intramuscular (im) administration at two different dosing times (08:30h and 20:30h) to dogs, in order to determine whether time-of-day administration modifies ceftazidime pharmacokinetics andor predicted clinical antipseudomonal efficacy. Six female healthy beagle dogs were administered ceftazidime pentahydrate by the intramuscular route in a single dose of 25mgkg at both 08:30 and 20:30h, two weeks apart. Plasma ceftazidime concentrations were determined by microbiological assay. Pharmacokinetic parameters and time above the minimum inhibitory concentration (T>MIC) and 4xMIC for Pseudomonas aeruginosa were calculated from the disposition curve of each dog. No differences between the daytime and nighttime administrations were found for the main pharmacokinetic parameters, including Cmax, tmax, t λ, AUC, and MRT; however, the high interindividual variability shown by these values and the small number of individuals may account for this lack of difference. Rate of absorption (ka) was significantly higher after the 20:30h than 08:30h administration. No significant differences between T>MIC were found when comparing the 08:30h and 20:30h administrations. Mean T>MIC values predicted a favorable bacteriostatic effect for all susceptible strains of P. aeruginosa for the 12h dosing interval at both dosing times. Our results suggest that similar antipseudomonal activity may be expected when ceftazidime is administered at 8:30 and 20:30h; however, as only two timepoints of drug administration were explored, we are unable to draw any conclusions for other treatment times during the 24h.