Assessment of the long-acting ivermectin formulation in sheep: Further insight into potential pharmacokinetic interactions.

The aim of the current study was to evaluate the in vivo pharmacokinetic of ivermectin (IVM) after the administration of a long-acting (LA) formulation to sheep and its impact on potential drug-drug interactions. The work included the evaluation of the comparative plasma profiles of IVM administered at a single therapeutic dose (200 µg/kg) and as LA formulation at 630 µg/kg. Additionally, IVM was measured in different gastrointestinal tissues at 15 days posttreatment with both IVM formulations. The impact of the long-lasting and enhanced IVM exposure on the disposition kinetics of abamectin (ABM) was also assessed. Plasma (IVM and ABM) and gastrointestinal (IVM) concentrations were analyzed by HPLC with fluorescent detection. In plasma, the calculated Cmax and AUC0-t values of the IVM-LA formulation were 1.47- and 3.35-fold higher compared with IVM 1% formulation, respectively. The T1/2ab and Tmax collected after administration of the LA formulation were 2- and 3.5-fold longer than those observed after administration of IVM 1% formulation, respectively. Significantly higher IVM concentrations were measured in the intestine mucosal tissues and luminal contents with the LA formulation, and in the liver, the increase was 7-fold higher than conventional formulation. There was no drug interaction between IVM and ABM after the single administration of ABM at 15 days post-administration of the IVM LA formulation. The characterization of the kinetic behavior of the LA formulation to sheep and its potential influence on drug-drug interactions is a further contribution to the field.

Ivermectin dissipation and movement from feces to soil under field conditions.

The aim of this work was to evaluate the fate of ivermectin (IVM) at two concentrations in cattle feces and its movement to the nearby soil and plants. Feces were spiked with IVM at two levels: 3000 ng g-1 (high group, HG) and 300 ng g-1 (low group, LG). Artificial dung pats were prepared and deposited in an experimental field area. Feces and underlying soil were sampled up to 60 days post-deposition (dpd). As an additional analysis, grasses growing around the pats were sampled at 30 and 60 dpd. Ivermectin concentrations in all matrices were determined by HPLC. Mean IVM fecal concentrations were in the range between 3901.9 ng g-1 and 2419.2 ng g-1 (high group) and 375.3 ng g-1 and 177.49 ng g-1 (low group). Mean times for 50% and 90% dissipation were 88.23 and 293.03 days (HG) and 39.1 and 129.9 days (LG). Soil concentrations ranged from 26.1 ng g-1 to 71.1 ng g-1 (HG) and 3.4 to 5.9 ng g-1 (LG); in plants, concentrations were between 71.4 and 380.8 ng g-1 and 5.40 and 51.8 ng g-1 in HG and LG, respectively. These results confirm that IVM moves from feces to the underlying soil as well as to nearby plants. The potential risk of detrimental effects on soil organisms and the impact on herbivorous animals should be further evaluated.