Comparative pharmacokinetics of ivermectin alone and a novel formulation of ivermectin and rafoxanide in calves and sheep

This study investigated the comparative serum disposition kinetics of ivermectin (IVM) after a single subcutaneous dose of 200 microg/kg body weight of IVM alone or in combination with an anthelmintic consisting of ivermectin and rafoxanide (200 microg/kg of IVM and 2.5 mg/kg rafoxanide) for use in calves and sheep. The IVM concentrations in serum samples were analyzed by high-performance liquid chromatography with fluorescence detection. In sheep serum, rafoxanide induced a rapid absorption of IVM when given in combined form manifested by a shorter absorption half-life time of IVM by 68.49% when given in combination as compared with IVM when given alone. In addition, there is an increase in the value of the area under the concentration curve (AUC) by 15.48% while the value of elimination rate constant was decreased by 38.2% and significantly increased the half-life time of elimination from 2.04 days for IVM alone to 3.3 days when given in combination with rafoxanide. In calves serum, the mean t1/2ab for IVM/rafoxanide was 0.131 days and for the control formulation 0.16 days, and t1/2el was 5.78 and 4.95, respectively. IVM Cmax for IVM/rafoxanide was 22.4 ng/ml and for the control formulation 19.1 ng/ml. T (max) values were 0.99 and 1.12 days, and the mean AUC values were 188.9 and 165.4 ng/ml/day. The difference in Cmax, AUC, Kab, K el, and t1/2el was significant. However, there was no statistical difference between the Tmax and t1/2ab. These findings revealed that the combination of rafoxanide with IVM in sheep and calves increased the absorption of IVM and delayed its elimination.