COMPARATIVE PLASMA DISPOSITION KINETICS OF IVERMECTIN, MOXIDECTIN ANDDORAMECTIN IN CATTLE

The persistence of the broad-spectrum antiparasitic activity of endect ocide compounds relies on their disposition kinetics and pattern of pl asma/tissues exchange in the host. This study evaluates the comparativ e plasma disposition kinetics of ivermectin (IVM), moxidectin (MXD) an d doramectin (DRM) in cattle treated with commercially available injec table formulations. Twelve (12) parasite-free male Hereford calves (18 0-210 kg) grazing on pasture were allocated into three groups of four animals each. Animals in each group received either IVM (Ivomec 1%, MS D AGVET, Rahway, NJ, USA), MXD (Cydectin 1%, American Cyanamid, Wayne, NJ, USA) or DRM (Dectomax 1%, Pfizer Inc., New York, NY, USA) by subc utaneous injection at a dose of 200 mu g/kg. Jugular blood samples wer e collected from 1 h up to 80 days post-treatment, and plasma extracte d, derivatized and analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The parent molecules were detecte d in plasma between 1 h and either 70 (DRM) or 80 (IVM and MXD) days p ost-treatment. The absorption of MXD from the site of injection was si gnificantly faster (absorption half-life (t(1/2ab)) = 1.32 h) than tho se of IVM (t(1/2ab) = 39.2 h) and DRM (t(1/2ab) = 56.4 h). MXD peak pl asma concentration (C-max) was reached significantly earlier (8.00 h) compared to those of IVM and DRM (4-6 days post-treatment). There were no differences on C-max values; the area under the concentration-time curve (AUC) was higher for IVM (459 ng.d/mL) and DRM (627 ng.d/mL) co mpared to that of MXD (217 ng.d/mL). The mean plasma residence time wa s longer for MXD (14.6 d) compared to IVM (7.35 d) and DRM (9.09 d). U nidentified metabolites were detected in plasma; they accounted for 5. 75% (DRM), 8.50% (IVM) and 13.8% (MXD) of the total amount of their re spective parent drugs recovered in plasma, The comparative plasma disp osition kinetics of IVM, MXD and DRM in cattle, characterized over 80 days post-treatment under standardized experimental conditions, is rep orted for the first time.