Comparative plasma ampicillin levels and bioavailability of five parenteral ampicillin formulations in ruminant calves

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Abstract
Plasma ampicillin concentrations were determined in an eight‐ways crossover trial involving six ruminant calves, which were treated intravenously (i.v.) with sodium ampicillin at 15.5 mg/kg and intramuscularly (i.m.) with five different ampicillin trihydrate or ampicillin anhydrate formulations at 7.7 mg/kg. The mean plasma concentration‐time curve (Cp)after intravenous ampicillin sodium administration was described biexponentially, as: Cp = 38.8 e ‐0.0268t + 0.45 e ‐0.0058t. Intramuscular injection, into the lateral neck, of Ampikel‐20® and Polyflex® resulted in 100 per cent bioavailabilities within 12 h post injection (p.i.), but the biological half‐lives (t½>) were different, being 2.1 and 3.8 h, respectively. Ampikel‐20® produced the hïghest peak plasma drug concentrations (mean C max:4.8 μg ampicillin/ml). After intramuscular injection of Penbritin® the mean bioavailability for the first 12 h p.i. was 63 per cent, the mean t½>, was 5.9 h, and the mean Cmax was 1.8 μg/ml. Treatment with Albipen® and Duphacillin® resulted in low plasma ampicillin levels, which were maintained for 3 to 6 days p.i., limited bioavailability during the first 12 h p.i., and a mean t½> of 22.2 and 11.9 h, respectively. Plasma concentrations of ampicillin from four hours onwards after i.m. and s.c. administration of Ampikel‐20® at a dose level of 15.5 mg/ kg were similar. The duration of potentially therapeutic plasma ampicillin concentrations after administration of each formulation is presented. Pre‐slaughter withdrawal times for diseased calves are suggested for the different formulations studied.