Elevation and prolongation of serum ampicillin and amoxycillin concentrations in calves by the concomitant administration of probenecid

Abstract

The effects of probenecid on serum ampicillin and amoxycillin concentrations were investigated in 1–5 week old calves after oral and parenteral drug administration. Ampicillin trihydrate was administered orally at 250mg/calf, after an overnight fast, alone and with 1.5g probenecid. Peak serum ampicillin concentrations were elevated from 0.60 to 1.22 μg/ml by the co‐administration of probenecid. In calves given 0.5 g amoxycillin trihydrate with the milk replacer, peak serum drug concentration increased from 1.74 to 3.16 μg/ml when 1.5 g probenecid was given too. Maximal effect of probenecid administered orally was with the 1.5 g/calf dose with considerably lesser increase in peak serum amoxycillin being observed with doses of 0.5 g, 1 g and 2 g/calf. After parenteral injection of probenecid solution at 1 g and 2 g/calf serum ampicillin concentrations peaked at more than twice the concentrations measured after equal doses of the two antibiotics were injected alone. The co‐administration of 2 g probenecid and 1 g sodium ampicillin or 0.5 g sodium amoxycillin parenterally resulted in peak antibiotic concentrations considered to be effective against some of the more resistant pathogenic Gram‐negative bacteria associated with diseases in calves and serum antibiotic concentrations 5 μg/ml were maintained during 5–6 h as opposed to 2–3 h after the antibiotics were injected alone. Oral administration of 1.5 g probenecid at three consecutive milk feeding times did not alter serum urea or serum creatinine concentrations.