The effect of feed intake level on the pharmacokinetic disposition of closantel in sheep.

Closantel (CLS), containing a trace of [14C]CLS, was administered intraruminally to sheep whose feed intake was maintained at either 800 or 400 g day-1. The kinetic disposition of [14C]metabolites was determined in rumen and abomasal fluid and particulate digesta and of CLS per se in plasma. The slower digesta flow rate in the sheep on low, compared with high, feed intake resulted in the proportion of the dose passing through the abomasum being reduced from 60 to 45%. Increased absorption of CLS from the rumen of sheep on low feed intake resulted in both higher maximum CLS concentration and greater area under CLS plasma concentration versus time curve, although the elimination half-life was independent of feed intake. Not only are the higher plasma CLS concentrations likely to increase efficacy against Haemonchus contortus, the threshold concentrations that are considered to inhibit the establishment of ingested H. contortus larvae were extended by 10-14 days. The extended CLS presence after reduced feeding, when integrated with parasite treatment programmes, provides an opportunity to reduce the impact of H. contortus infection.