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

The plasma pharmacokinetics of doramectin and invermectin after topical administration (500 mu g kg(-1)) were compared over a 50-day period in 24 young beef cattle. Observed maximum concentration (C-max) and time to maximum concentration (T-max) 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 C-max of doramectin (12.2 +/- 4.8 ng ml(-1)) and ivermectin (12.2 +/- 6.0 ng ml(-1)) and T-max 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 mu g kg(-1) pour-on administration of doramectin and ivermectin led to an overall exposure as reflected by the mean AUG, 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. (C) 1999 Elsevier Science B.V. All rights reserved.