Effect of induced synovial inflammation on pharmacokinetics and synovial concentration of sodium ampicillin and kanamycin sulfate after systemic administration in ponies

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Abstract
Single doses of sodium ampicillin (10 mg/kg) and kanamycin sulfate (5 mg/kg) were administered intramuscularly (i.m.) separately, and then together, to five pony mares. The plasma antibiotic concentration-time curves were constructed. The pharmacokinetic parameters of the antibiotics given separately were not altered by concurrent administration. Four of the five pony mares were then given the i.m. kanamycin/ampicillin combination 4 h after acute synovitis and fever had been induced by injection of lipopolysaccharide into the left intercarpal joint. The plasma concentration-time curves and the synovial concentration-time curves of inflamed and normal joints were constructed. The Cmax of ampicillin in the lipopolysaccharide experiment was significantly higher than in the other experiments. The antibiotics entered the synovial fluid of the inflamed joints more quickly and attained higher concentrations than in the uninflamed joints. The ampicillin concentration exceeded 5 .mu.g/ml in inflamed synovial fluid for some 2.5 h after injection, and kanamycin sulfate concentration exceeded 2 .mu.g/ml for 7 h.