Bioequivalence of ivermectin formulations in pigs and cattle

The vehicle in which endectocide compounds are formulated plays a relevant role in their absorption kinetics and resultant systemic availability, The pharmaceutical bioequivalence and comparative plasma disposition kinetics o f ivermectin (NM), following the subcutaneous administration of two injecta ble formulations to pigs and cattle were investigated using parallel experi mental designs, Sixteen parasite-free male Duroc Jersey-Yorkshire crossbred pigs (90-110 kg) (Expt 1) and 16 parasite-free male Holstein calves (100-1 20 kg) (Expt 2) were divided into two groups and treated subcutaneously at either 300 (pigs) or 200 (calves) mu g/kg with two different propylene glyc ol/glycerol formal (60:40) based NM formulations; in both experiments pigs or calves in Group A received the test (NM-TEST) formulation and those in G roup B were treated with the reference formulation (IVM-CONTROL). Hepariniz ed blood samples were taken from 0 h up to either 20 (pigs) or 30 (calves) days post-treatment and plasma was extracted, derivatized and analysed by h igh performance liquid chromatography (HPLC) using fluorescence detection. Early detection of NM (12 h) with a peak plasma concentration (C-max) betwe en 33 and 39 ng/mL was observed in pigs. The drug was detected in plasma up to 20 days postadministration of either formulation, resulting in eliminat ion half-lives between 3.47 and 3.80 days, There were no differences betwee n the NM-TEST and IVM-CONTROL formulations in the kinetic parameters (excep t t(max)) obtained in pigs, IVM was detected in plasma between 12 h and 30 days postadministration of both formulations under investigation in cattle, The plasma disposition kinetics of IVM in calves was similar following tre atment with both formulations. C-max values (between 40.5 and 46.4 ng/mL) w ere achieved at 2 days post-administration of both formulations. None of th e estimated kinetic parameters were statistically different between drug fo rmulations. The injectable IVM formulations investigated were bioequivalent after their subcutaneous administration to both pigs and calves at recomme nded dose rates.