Plasma pharmacokinetics and faecal excretion of ivermectin, doramectin and moxidectin following oral administration in horses

Abstract

The present study was carried out to investigate whether the pharmacokinetics of avermectins or a milbemycin could explain their known or predicted efficacy in the horse. The avermectins, ivermectin (IVM) and doramectin (DRM), and the milbemycin, moxidectin (MXD), were each administered orally to horses at 200 mug/kg bwt. Blood and faecal samples were collected at predetermined times over 80 days (197 days for MXD) and 30 days, respectively, and plasma pharmacokinetics and faecal excretion determined. Maximum plasma concentrations (C-max) (IVM: 21.4 ng/ml; DRM: 21.3 ng/ml; MXD: 30.1 ng/ml) were obtained at 7.9 h (IVM), 8 h (DRM) and 7.9 h (MXD). The area under the concentration time curve (AUC) of MXD (92.8 ng.day/ml) was significantly larger than that of IVM (46.1 ng.day/ml) but not of DRM (53.3 ng.day/ml) and mean residence time of MXD (17.5 days) was significantly longer than that of either avermectin, while that of DRM (3 days) was significantly longer than that of IVM (2:3 days). The highest (dry weight) faecal concentrations (IVM: 19.5 mug/g; DRM: 20.5 mug/g; MXD: 16.6 mug/g) were detected at 24 h for all molecules and each compound was detected (greater than or equal to 0.05 mug/g) in faeces between 8 h and 8 days following administration. The avermectins and milbemycin with longer residence times may have extended prophylactic activity in horses and may be more effective against emerging and maturing cyathostomes during therapy. This will be dependent upon the relative potency of the drugs and should be confirmed in efficacy studies.