Pharmacokinetics of extended-release ivermectin microspheres after oral administration to healthy pigs.

We compared the pharmacokinetics of ivermectin premix and ivermectin microspheres in pigs after single and multiple administration regimes. In the single-dose experiments, 24 piglets were randomly divided into three groups and given ivermectin at 0.3 mg/kg using (a) 1.0% ivermectin administered subcutaneously, (b) 0.25% ivermectin premix orally, and (c) 0.25% ivermectin microspheres orally. In the multiple-dose experiment, 6 pigs in two equal groups received ivermectin premix and microspheres orally at 0.3 mg/kg for 7 consecutive days to monitor the valley plasma levels. The plasma samples were detected by fluorescence high-performance liquid chromatography, and concentration-time data were fitted to a noncompartmental model. After oral administration of ivermectin microspheres at a single dose, the elimination rate constant (Kel), the half-life (t1/2 ), the peak time (Tmax ), the mean residence time (MRT), and the peak concentration (Cmax ) were 0.012 +/- 0.0031/hr, 59.94 +/- 20.18 hr, 9.50 +/- 0.93 hr, 55.96 +/- 11.40 hr, and 37.75 +/- 3.45 ng/ml, respectively. The Cmax of microspheres was not statistically different (p > .05) compared with that of premix groups (39.81 +/- 5.83 ng/ml). Moreover, the AUC of the microcapsule groups was increased from 1,129.76 +/- 245.62 to 1,607.33 +/- 343.35 hr ng/ml compared with the premix groups, and the relative bioavailability increased by an average of 17.53% after oral administration with ivermectin microspheres. Multiple-dose administration also indicated pigs fed with ivermectin microspheres can get a higher minimum steady-state concentration and a longer maintenance time than ivermectin premix.