Intramuscular dosing strategy for ampicillin sodium in horses, based on its distribution into tissue chambers before and after induction of inflammation

The Pharmacokinetics (PK) and distribution into tissue chamber fluid (TCF) of intramuscularly (i.m.) administered ampicillin sodium were examined in horses in order to design adequate dosing strategies. Concentration–time curves of ampicillin in plasma and TCF were determined in six horses following administration of 15 mg/kg ampicillin sodium, before and after the induction of local inflammation with 0.5% carrageenan. The calculated parameters were used to simulate various dosage–dosing interval combinations. Ampicillin was absorbed very rapidly following i.m. administration. Plasma concentrations were maximual between 18 and 21 min after administration. None of the plasma PK parameters were affected significantly by local (TC) inflammation. Penetration of ampicillin into and elimination from the TCF were affected significantly by inflammation and the half-life of elimination from the tissue fluid t1/2(d) was significantly shorter in inflammation. In the simulated dosage–dosing interval scenarios, only a dosage of 15 mg ampicillin/kg four times daily would successfully treat all ampicillin-susceptible bacterial isolates in well vascularized tissues. However a dosage as low as 10 mg/kg twice daily, would, in theory, treat all ampicillin-susceptible isolates in the inflamed poorly vascularized tissues. Decreasing the dosage results in loss of efficacy that cannot be completely compensated for by increasing the frequency of dosing.