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

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 (t1/2) were different, being 2.1 and 3.8 h, respectively. Ampikel-20 produced the highest peak plasma drug concentrations (mean C max :4.8 microgram ampicillin/ml). After intramuscular injection of Penbritin the mean bioavailability for the first 12 h p.i. was 63 per cent, the mean t1/2 was 5.9 h, and the mean Cmax was 1.8 microgram/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 t1/2 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.