Effects of Probenecid on Blood Levels and Tissue Distribution of Ampicillin in Fowls and Turkeys

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Abstract
The effect of probenecid (a benzoic acid derivative which competitively inhibits active secretion of weak organic acids by the renal tubules) on serum ampicillin concentrations and the distribution of ampicillin in body organs was examined in fowls and turkeys. An aqueous solution of probenecid co-administered i.m. at 200 mg/kg with sodium ampicillin solution at 25 mg/kg resulted in peak serum antibiotic concentration of 16.5 .mu.g/ml. A similar dose of ampicillin administered alone produced a peak level of 4.6 .mu.g/ml. S.c. injections of sodium ampicillin at 25 mg/kg with aqueous probenecid at 200 mg/kg resulted in a peak serum ampicillin concentration (12.8 .mu.g/ml) 3 times as high as the peak produced by the s.c. injection of ampicillin alone at 50 mg/kg (4.2 .mu.g/ml). The elimination half-life (t1/2) of the drug (30 min) was increased to 1.5 h by co-administration of probenecid parenterally, and serum antibiotic levels .gtoreq. 5.0 .mu.g/ml were maintained during 3 h. Ampicillin seemed poorly absorbed from the gastrointestinal tract of fowls. A single oral bolus administration of ampicillin trihydrate aqueous suspension produced a peak of 0.6 .mu.g/ml, and co-administrations of aqueous probenecid suspension at 20, 50, and 100 mg/kg, respectively, produced peaks of 0.9, 1.25 and 1.5 .mu.g/ml. During 4 and 5 days, when ampicillin was added to the drinking water at rates of 200 and 50 mg/l, serum ampicillin levels were rather low (peaks of 0.20 and 0.12 .mu.g/ml, respectively) and although these levels were increased by 50% with the co-administration of probenecid they were considered of limited clinical value for treating systemic bacterial infections. Probenecid did not change the distribution of ampicillin in the organs.

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