Pharmacokinetics of ivermectin in sheep following pretreatment with Escherichia coli endotoxin.

Abstract

The comparative pharmacokinetics of ivermectin (IVM), between healthy and in Escherichia coli lipopolysaccharides (LPS) injected sheep, was investigated after an intravenous (IV) administration of a single dose of 0.2mg/kg. Ten Suffolk Down sheep, 55±3.3kg, were distributed in two experimental groups: Group 1 (LPS): treated with three doses of 1μg LPS/kg bw at -24, -16, and -0.75hr before IVM; group 2 (Control): treated with saline solution (SS). An IV dose of 0.2mg IVM/kg was administered 45min after the last injection of LPS or SS. Plasma concentrations of IVM were determined by liquid chromatography. Pharmacokinetic parameters were calculated based on non-compartmental modeling. In healthy sheep, the values of the pharmacokinetic parameters were as follows: elimination half-life (2.85days), mean residence time (MRT) (2.27days), area under the plasma concentration curve over time (AUC, 117.4ng day-1 ml-1 ), volume of distribution (875.6ml/kg), and clearance (187.1ml/day). No statistically significant differences were observed when compared with the results obtained from the group of sheep treated with LPS. It is concluded that the acute inflammatory response (AIR) induced by the intravenous administration of E.coli LPS in adult sheep produced no changes in plasma concentrations or in the pharmacokinetic behavior of IVM, when it is administered intravenously at therapeutic doses.