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Effects of probenecid on blood levels and tissue distribution of ampicillin in fowls and turkeys.

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 coadministered intramuscularly, at 200 mg/kg, with sodium ampicillin solution, at 25 mg/kg, resulted in peak serum antibiotic concentration of 16.5 microgram/ml. A similar dose of ampicillin administered alone produced a peak level of 4.6 microgram/ml. Subcutaneous injections of sodium ampicillin at 25 mg/kg with aqueous probenecid at 200 mg/kg resulted in a peak serum ampicillin concentration (12.8 microgram/ml) three times as high as the peak produced by the subcutaneous injection of ampicillin alone at 50 mg/kg (4.2 microgram/ml). The elimination half-life (t 1/2) of the drug (30 min) was increased to 1.5 hr by coadministration of probenecid parenterally, and serum antibiotic levels greater than or equal to 5.0 microgram/ml were maintained during 3 hours. Ampicillin seemed to be poorly absorbed from the gastrointestinal tract of fowls. A single oral bolus administration of ampicillin trihydrate aqueous suspension produced a peak of 0.6 microgram/ml, and coadministrations of aqueous probenecid suspension at 20, 50, and 100 mg/kg respectively produced peaks of 0.9, 1.25, and 1.5 microgram/ml. During 4 and 5 days, when ampicillin was added to the drinking water at rates of 200 and 50 mg/liter, serum ampicillin levels were rather low (peaks of 0.20 and 0.12 microgram/ml, respectively), and although these levels were increased by 50% with the coadministration of probenecid they were considered to be of limited clinical value for treating systemic bacterial infections. Probenecid did not change the distribution of ampicillin in the organs.