Comparison of pharmacokinetic profiles of doramectin and ivermectin pour-on formulations in cattle

The plasma pharmacokinetics of doramectin and invermectin after topical administration (500 microg kg(-1)) were compared over a 50-day period in 24 young beef cattle. Observed maximum concentration (Cmax) and time to maximum concentration (Tmax) were determined directly from plasma concentrations for each animal. The area under the plasma concentration-time curve (AUC) and mean residence time (MRT) were calculated as indices of drug exposure and persistence. The Cmax of doramectin (12.2+/-4.8 ng ml(-1)) and ivermectin (12.2+/-6.0 ng ml(-1)) and Tmax of doramectin (4.3+/-1.6 days) and ivermectin (3.4+/-0.8 days) were not significantly different (p > 0.05). In contrast, the AUC of doramectin (168.0+/-41.7 ng day ml(-1)) was significantly greater than that of ivermectin (115.5+/-43.0 ng day ml(-1)). Furthermore, the range of AUC values calculated for ivermectin was wider than that obtained for doramectin, extending from 51.3 to 182.3 ng day ml(-1) for ivermectin versus 104.3-228.7 ng day ml(-1) for doramectin. The MRT was significantly greater for doramectin (12.8+/-1.9 days) than for ivermectin (8.4+/-1.5 days). It was concluded that a 500 microg kg(-1) pour-on administration of doramectin and ivermectin led to an overall exposure as reflected by the mean AUC, that was 45% higher for doramectin compared to ivermectin and that the relative inter-individual variability was less for doramectin than for ivermectin. Possible therapeutic consequences of these differences between doramectin and ivermectin pour-on formulations are discussed.