CHRONOKINETICS OF CEFTAZIDIME AFTER INTRAMUSCULAR ADMINISTRATION TO DOGS

Abstract

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 (08:30 h and 20:30 h) to dogs, in order to determine whether time-of-day administration modifies ceftazidime pharmacokinetics and/or predicted clinical antipseudomonal efficacy. Six female healthy beagle dogs were administered ceftazidime pentahydrate by the intramuscular route in a single dose of 25 mg/kg at both 08:30 and 20:30 h, 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 C_max, t_max, t_{½ 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 (k_a) was significantly higher after the 20:30 h than 08:30 h administration. No significant differences between T > MIC were found when comparing the 08:30 h and 20:30 h administrations. Mean T > MIC values predicted a favorable bacteriostatic effect for all susceptible strains of P. aeruginosa for the 12 h dosing interval at both dosing times. Our results suggest that similar antipseudomonal activity may be expected when ceftazidime is administered at 8:30 and 20:30 h; however, as only two timepoints of drug administration were explored, we are unable to draw any conclusions for other treatment times during the 24 h. (Author correspondence: [email protected]).

Keywords:

• Chronopharmacology
• Chronokinetics
• Antibiotics
• Ceftazidime
• Dogs
• Circadian rhythms
• Cephalosporin
• Pseudomonas aeruginosa

ACKNOWLEDGMENTS

The authors wish to thank Laboratorios Richet, Buenos Aires, Argentina, for kindly providing the drug used in this study, and Claudio Pacheco for technical assistance with dogs.