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Home » Archive » 2008

TDK conference 2008

Pharmacokinetic investigation of the amoxicillin-clavulanic acid combination in chickens and sensitivity of Salmonella spp., E. coli and Pasteurella spp. to the combination
Tóth István - year 5
Department of Pharmacology and Toxicology
Supervisor: Dr. Jerzsele Ákos

Abstract:

In the poultry industry prevention and treatment of bacterial infections with antibiotics have a high economic importance. The clavulanate potentiated amoxicillin may be a good choice for this purpose according to its large therapeutic index and broad antibacterial spectrum. In our experiments the pharmacokinetic behaviour of the two substances were studied in broiler chickens after intravenous and oral administration at a dose of 12,5 mg/kg bw. The other part of our study was to determine the MIC values of the Salmonella enterica, Pasteurella multocida and Escherichia coli strains in Hungary isolated from chickens. The objective was to lay down a recommendation of the correct therapy in broiler chickens.

Twelve broiler chickens were treated with the amoxicillin-clavulanic acid combination orally and intravenously in a cross-over study. The plasma concentrations of the agents were determined using RP-HPLC and UV-detection at 210 nm. Data collected were subjected to compartmental analyses. The sensitivity of pathogenic bacteria to the combination were estimated by testing 59 Salmonella, 40 Pasteurella and 69 E. coli strains derived from chickens. Agar-dilution method was used to determine MIC50 and MIC90 values.

The disposition curves for both drugs after intravenous administration were best described by a two-compartmental open model. Significant differences (p<0.05) were found in absorption, distribution, and elimination half-life, clearance, volume of distribution, and MRT between amoxicillin and clavulanic acid. This means that amoxicillin has slower distribution and better penetration in the tissues and elimination is slower as well. However, these differences are only slight deviations, so it can be concluded that the pharmacokinetic profile of the two substances are similar, which enhances the synergistic effect of the combination.

The MIC90 values for the amoxicillin-clavulanic acid combination in Salmonella and Pasteurella spp. were found to be 2 μg/ml, and 16 μg/ml in E. coli. It has been found that the MIC90 values of the strains tested were found lower in the case of amoxicillin-clavulanic acid combination than that of amoxicillin alone.

In view of the pharmacokinetic parameters of the combination and MIC90 values for important pathogenic strains, therapeutic recommendations have been given for the usage of the amoxicillin-clavulanic acid combination in broiler chickens against infections caused by the above-mentioned bacteria.



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