Bioavailability of oral penicillins in the horse: a comparison of pivampicillin and amoxicillin

Abstract

The pharmacokinetics of ampicillin and amoxicillin following intravenous administration at a dose rate of 15 and 10 mg/kg respectively were studied in four healthy adult horses. Pharmacokinetics of pivampicillin and amoxicillin were studied after oral administration to four healthy adult horses. Pivampicillin, a prodrug of ampicillin, was administered orally to starved and fed horses at a dose rate of 19.9 mg/kg, which is equivalent on a molecular basis to 15 mg/kg ampicillin. Amoxicillin was administered orally to starved horses only, at a dose rate of 20 mg/kg. Ampicillin and amoxicillin concentrations in plasma, synovial fluid and urine were determined. Mean biological half-life of intravenously administered ampicillin and amoxicillin was 1.72 and 1.43 h respectively, whilst the distribution volume (Vss) appeared to be 0.180 and 0.192 1/kg. Orally administered pivampicillin and amoxicillin were rapidly absorbed. A maximum concentration in plasma of 3.80 micrograms/ml was reached 2 h after administration of pivampicillin to starved horses; in fed horses a maximum concentration of 5.12 micrograms/ml was reached 1 h after administration. After oral administration of amoxicillin a maximum concentration of 2.03 micrograms/ml was reached after 1 h. The (absolute) bioavailability of pivampicillin administered orally was 30.9% in starved horses and 35.9% in fed horses. The bioavailability of amoxicillin administered orally was 5.3% in starved horses.

Some pharmacokinetic parameters of ampicillin/sulbactam combination after intravenous and intramuscular administration to goats

“…Using Akaike's information criterion (AIC) (33), we fitted the ampicillin and sulbactam plasma concentration vs time data after intravenous administration of the combination preparation to a two-compartment open model. This conclusion is in agreement with that found in previous studies of ampicillin carried out in various animals species (8,11,21,22,30) and in humans (5,14). However, the data for sulbactam are reported to best fit a two-compartment model in sheep and a one-compartment model in calves when the same combination of drugs was administered (20).…”

“…No significant differences between ampicillin and sulbactam after intravenous administration were found in the apparent volume of distribution, calculated by the area method (Varea). The ampicillin Varea value is similar to that reported in sheep (22), greater than the value reported in dogs of 0.27 1/kg (2), but smaller than the values reported for other animal species (1,8,11). Perhaps the most important kinetic parameter is the half-life (t112p).…”

“…Perhaps the most important kinetic parameter is the half-life (t112p). The half-life of ampicillin after intravenous administration (19.2 min) was similar to that reported in sheep (30) but shorter than that reported for horses (11,27) cows (21), sheep (22), and goats (1). The mean half-life of sulbactam in the present study was shorter than that obtained in sheep (1.55 h), but similar to the value reported for calves (0.72 h) (20).…”

Comparative Veterinary Pharmacokinetics

“…Bioavailability of several drugs can be very low compared to other domestic species. Examples include several antibiotics, like ampicillin and amoxicillin that have 0-1% and 5% oral bioavailability, respectively (Ensink et al 1992, Ensink et al 1996. This phenomenon can result in severe dysbacteriosis because of the low extent of absorption and accumulation of the substance in the intestinal lumen.…”

“…Namely, oral bioavailability values show pronounced differences between animal species. The frequently applied broad spectrum aminopenicillin, amoxicillin shows an oral bioavailability of 5% in horses (Ensink et al, 1992), 28-33% in swine (Agerso&Friis, 1998), 59-68% in poultry (El Sooud et al, 2004, Jerzsele et al, 2009, Jerzsele et al, 2011 and 60-80% in dogs and cats (Küng et al, 1994).…”