Moxidectin in cattle: correlation between plasma and target tissues disposition

The time of parasite exposure to active drug concentrations determines the persistence of the antiparasitic activity of endectocide compounds. This st udy evaluates the disposition kinetics of moxidectin (MXD) in plasma and in different target tissues following its subcutaneous (s.c.) administration to cattle, Eighteen male, 10-month old Holstein calves weighing 120-140 kg were subcutaneously injected in the shoulder area with a commercially avail able formulation of MXD (Cydectin 1%, American Cyanamid, Wayne, NJ, USA) at 200 mu g/kg. Two treated calves were killed at each of the following times post-treatment: 1, 4, 8, 18, 28, 38, 48, 58 and 68 days. Abomasal and smal l intestine mucosal tissue and fluids, bile, faeces, lung, skin and plasma samples were collected, extracted, derivatized and analysed to determine MX D concentrations by high performance liquid chromatography (HPLC) with fluo rescence detection. MXD was extensively distributed to all tissues and flui ds analysed, being detected (concentrations > 0.1 ng/g; ng/mL) between 1 an d 58 days post-treatment. MXD peak concentrations were attained during the first sampling day. MXD maximum concentration (C-max) values ranged from 52 .9 (intestinal mucosa) up to 149 ng/g (faeces). The mean residence time (MR T) in the different tissues and fluids ranged from 6.8 (abomasal mucosa) up to 11.3 (bile) days. MXD concentrations in abomasal and intestinal mucosal tissue were higher than those detected in plasma; however, there was a hig h correlation between MXD concentrations observed in plasma and those detec ted in both gastrointestinal mucosal tissues. MXD concentrations were marke dly greater in the mucosa than in its respective digestive fluid (P < 0.01) , MXD concentrations in skin were higher than those found in plasma (P < 0. 01). Drug concentrations recovered in the dermis were greater than those de tected in the hypodermal tissue (P < 0.05). Large concentrations of MXD wer e excreted in bile and faeces. These findings may contribute to an understa nding of the relationship between the kinetic behaviour and the persistence of the antiparasite activity of MXD against different ecto-endoparasites i n cattle.