THE EFFECT OF FEED-INTAKE LEVEL ON THE PHARMACOKINETIC DISPOSITION OFCLOSANTEL IN SHEEP

Closantel (CLS), containing a trace of [C-14]CLS, was administered int raruminally to sheep whose feed intake was maintained at either 800 or 400 g day(-1). The kinetic disposition of [C-14]metabolites was deter mined in rumen and abomasal fluid and particulate digests and of CLS p er se in plasma. The slower digesta how rate in the sheep on low, comp ared with high, feed intake resulted in the proportion of the dose pas sing through the abomasum being reduced from 60 to 45%. Increased abso rption of CLS from the rumen of sheep on low feed intake resulted in b oth higher maximum CLS concentration and greater area under CLS plasma concentration versus time curve, although the elimination half-life w as independent of feed intake. Not only are the higher plasma CLS conc entrations likely to increase efficacy against Haemonchus contortus, t he threshold concentrations that are considered to inhibit the establi shment of ingested H. contortus larvae were extended by 10-14 days. Th e extended CLS presence after reduced feeding, when integrated with pa rasite treatment programmes, provides an opportunity to reduce the imp act of H. contortus infection. (C) 1997 Australian Society for Parasit ology. Published by Elsevier Science Ltd.