Effect of the injection site on the bioavailability of amoxycillin trihydrate in dairy cows

Abstract

The pharmacokinetic behaviour of amoxycillin sodium and amoxycillin trihydrate‐20% aqueous suspension was studied in a group of five dairy cows. Amoxycillin sodium was administered intravenously and amoxycillin trihydrate‐20% by four different routes of administration: subcutaneously in the dewlap, intramuscularly in the lateral neck, M. triceps, and buttock (M. semitendineus). The dose level for both drug formulations was 3.83 ± 0.47 mg/kg.The mean plasma concentration–time curve(Cp)for intravenous amoxycillin sodium administration could be described mathematically by the biexponential equation Cp= 15.6 e‐0.033t+ 1.04 e‐0.0091t. The areas under the plasma concentration–time curve (AUC's) obtained after the intravenous injections of sodium amoxycillin were used as references for the bioavailability studies of the four routes of amoxycillin trihydrate administration.Intramuscular injections into the lateral neck or into the M. triceps resulted in similar systemic bioavailabilities, being at 12 h post injection (p.i.) 76.2 and 79.2% of the administered dose. The biological half‐lives (t1/2) were similar, being 6.2 and 6.9 h, respectively. After subcutaneous injection into the dewlap or intramuscular injection into the buttock lower bioavailabilities at 12 h p.i. were observed (24.1 and 49.2%, respectively). The plasma amoxycillin concentration was persistently low. The half‐lives of plasma amoxycillin disposition after the buttock and dewlap injections were 13.2 and 44 h, respectively.The plasma concentrations obtained were compared with minimal inhibitory concentrations (MIC) against pathogenic bacteria with respect to the theoretical design of effective antibacterial therapy. The differences observed serve to emphasize the fact that more attention should be paid to the effect of the route of administration on the biological bioavailability of a drug, with particular reference to studies on clinical efficacy. Pre‐slaughter withdrawal times were suggested for the different routes of injection of these two drug formations.