Ivermectin pharmacokinetics in lactating sheep.

Ivermectin (IVM) concentrations in plasma and milk were studied in six Istrian Pramenka dairy sheep after a single subcutaneous dose of 0.2 mg/kg b.w. of IVM in the early lactation period to describe IVM disposition in milk and to evaluate the transfer of IVM residues via milk to suckling lambs. Large inter-animal in concentration variability of IVM in both matrices was observed. The highest overall concentration was found in the same animal: 21.7 microg/l of H(2)B(1a) in plasma on the second day and 44.9 microg/kg of H(2)B(1a) in milk on the first day after the drug was administered. The mean time in which IVM concentrations fell below the limit of detection for the whole ewe group was 22 and 23 days for plasma and milk, respectively. Time course of IVM concentration in milk was following the time course of IVM concentration in plasma, with an overall mean+/-S.D. of milk/plasma ratio of 1.67+/-0.50 for the first 7 days of the experiment. A mean of 0.7% of the dose was excreted through milk. Individual pharmacokinetic parameters were determined by fitting a one-compartment model to the milk and plasma concentration-time profiles. Mean t(max), c(max), t(1/2k(e)) and AUC values for plasma data were: 1.70+/-0.65 days, 11.88+/-6.96 microg/l, 2.85+/-1.97 days and 63.99+/-28.34 microg day/l, respectively, and for milk: 1.28+/-1.07 days, 22.67+/-18.27 microg/l, 3.56+/-2.01 days and 114.60+/-60.41 microg day/l, respectively. The highest level of concentration in suckling lamb plasma, 0.36 microg/l of H(2)B(1a), was slightly above the limit of determination. The mean lamb to ewe ratio of areas under the plasma concentration-time curve for the first 5 days was 0.02. On the basis of obtained results, it can therefore be claimed that indirect IVM exposure of the suckling lambs via milk was negligible.