Distribution and Elimination of the Third Generation Cephalosporins in Dogs: A Comparative Study

Abstract

Members of the third generation of cefalosporins are well regarded as a therapeutic choice due to their extended bactericidal effect against gram-negative pathogenic bacteria in addition to their pharmacokinetics-pharmacodynamics favorable features. Cefatoxime is active against gram-negative bacilli and Streptococci in contrast to Pseudomonas aeruginosa, while, Ceftazidime shows a greater antibacterial activity against P. aeruginosa. pharmacokinetic studies of Ceftazidime and Cefotaxime in local Mongrel dogs are almost non-existent. Therefore, this study aims to enrich the therapeutic profile of the third generation of cefalosporins with data by subjecting each ceftazidime and cefotaxime to study their distribution and elimination features, and to compare their pharmacokinetic profiles. The pharmacokinetic study ran a crossover design where a single intravenous bolus of Ceftazidime (20 mg/kg) was administered. then, after a washout period of two weeks, a bolus of Cefotaxime (25 mg/kg) was injected intravenously. The microbiological assay was used to find the concentrations of the two antibiotics. The Noncompartmental pharmacokinetic model was applied to calculate the distribution and elimination parameters of Ceftazidime and Cefotaxime. The results found the concentration at zero time (C0) and the areas under the curve (AUC & AUMC) parameters were significantly higher in the plasma of the dogs that were given Ceftazidime compared to those whom Cefotaxime administered. In contrast, Cefotaxime displayed larger volumes of distribution (Vdss and Vz ) than Ceftazidime. The mean residence time (MRT) and the half-life (t1/2) are longer in Cefotaxime than in Ceftazidime, also body clearance (Cl) was higher in Cefotaxime.
The Study concluded that the distribution and elimination of Ceftazidime and Cefatoxime in local mongrel dogs is slightly variable compared to the distribution and elimination in most recent studies done on dogs considering the difference in dose, the useddog species, the method of analysis, and the pharmacokinetics calculations. and, the comparison between the two drugs showed a better distribution of Cefatoxime to the peripheral tissues, a longer half-life, and a mild rapid elimination compared to Ceftazidime which achieved a greater concentration at the zero time accompanied by a larger area under the curve, such as paradoxical events may require a further study for the pharmacokinetics of both drugs especially Cefatoxime due to lack of adequate and recent pharmacokinetic studies for this drugs in dogs compared to Ceftazidime.