Moxidectin in cattle: correlation between plasma and target tissues disposition

Abstract

The time of parasite exposure to active drug concentrations determines the persistence of the antiparasitic activity of endectocide compounds. This study 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 available formulation of MXD (Cydectin 1%, American Cyanamid, Wayne, NJ, USA) at 200 micrograms/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 small intestine mucosal tissue and fluids, bile, faeces, lung, skin and plasma samples were collected, extracted, derivatized and analysed to determine MXD concentrations by high performance liquid chromatography (HPLC) with fluorescence detection. MXD was extensively distributed to all tissues and fluids analysed, being detected (concentrations > 0.1 ng/g; ng/mL) between 1 and 58 days post-treatment. MXD peak concentrations were attained during the first sampling day. MXD maximum concentration (Cmax) values ranged from 52.9 (intestinal mucosa) up to 149 ng/g (faeces). The mean residence time (MRT) 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 high correlation between MXD concentrations observed in plasma and those detected in both gastrointestinal mucosal tissues. MXD concentrations were markedly 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 detected in the hypodermal tissue (P < 0.05). Large concentrations of MXD were excreted in bile and faeces. These findings may contribute to an understanding of the relationship between the kinetic behaviour and the persistence of the antiparasite activity of MXD against different ecto-endoparasites in cattle.

Enhancement of oral moxidectin bioavailability in rabbits by lipid co-administration

“…Previous findings ratified the relevance of plasma disposition kinetics in predicting the pattern of tissue distribution and the concentration profiles of moxidectin attained in target tissues where parasites are located (Lifschitz et al 1999). Thus, the antiparasitic activity of MLs is related to the presence of an effective concentration for a suitable length of time at the site of action.…”

In Vitro Efficacy of Moxidectin versus Ivermectin against Sarcoptes scabiei

“…Our results explain in part why single-dose moxidectin achieved 100% efficacy in pigs at day 14, compared to ivermectin's 62% efficacy (17). While moxidectin has excellent retention in the skin of pigs and cattle (34), different pharmacokinetics may relate to observed differences in treatment efficacy in other species. There have been few reports regarding the skin concentrations of ivermectin and moxidectin in humans.…”

Gene expression of ABC transporters in Cooperia oncophora after field and laboratory selection with macrocyclic lactones

“…In this study, the effect of IVM was compared before in vivo exposure and 10 days post-treatment. As the half-life of IVM in cattle is 16 days [30,31], the worms were exposed to the active drug at the time of collection. The most notable change observed in the present study was the up-regulation of Con-mrp1 and Con-pgp16.…”