Abstract
The use of topical (pour-on) administration of endectocide drugs in cattle has reached world-wide acceptance. However, only limited information is available on the kinetic behaviour for topically administered moxidectin (MXD). To improve our understanding of the relationship between pharmacokinetics and efficacy for pour-on preparations, MXD concentration profiles were measured in tissues of endo- and ectoparasites location over 35 days postadministration. MXD distribution to the fluid content and mucosal tissue of the abomasum and different intestinal sections (duodenum, ileum, caecum and colon) was assessed. The comparative patterns of MXD distribution to skin and hypodermic tissue from different anatomical sites (backline, rib cage, thigh and face) were also investigated following the pour-on administration. Wide tissue distribution and long residence time characterized the kinetics of topically administered MXD. MXD was recovered between 1 and 35 days post-treatment in all the tissues investigated. The highest MXD availabilities were observed in the skin layers at the site of administration (backline) and in the fat tissue. The fluid contents of different intestinal sections showed MXD concentrations higher than those measured in their respective mucosal tissues, particularly at day 1 post-treatment. MXD concentrations in the skin (epidermis + dermis) were higher than those measured in the hypodermic tissue. Large differences in the availability of MXD in skin from different anatomical regions (backline > rib cage > thigh > face) were observed. The low plasma and the high skin availability indicate the formation of a skin depot of the drug, being released slowly to the plasma and reaching concentrations in systemic tissues (abomasal mucosa, lungs, etc.) similar to those measured after subcutaneous administration. These findings demonstrate that target parasites may be exposed to markedly different drug concentrations according to their location sites, which is particularly relevant for ectoparasites located in different anatomical regions. Knowledge of the tissue distribution of topically administered endectocides contributes to understand the differences observed in efficacy and/or persistence of activity and to optimize their use in cattle.
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