Comparative distribution of ivermectin and doramectin to parasite locationtissues in cattle

Pharmacokinetic studies have been used traditionally to characterize drug c oncentration profiles achieved in the bloodstream. However, endectocide mol ecules exert their persistent and broad spectrum activity against parasites localized in many different tissues. The aim of this study was to compare the distribution of ivermectin (IVM) and doramectin (DRM) to different tiss ues in which parasites are found following subcutaneous administration to c alves. Holstein calves weighing 120-140 kg were injected in the shoulder ar ea with commercially available formulations of IVM (Ivomec 1% MSD AGVET, NJ , USA) (Group A) or DRM (Dectomax 1%, Pfizer, NY, USA) (Group B). Two treat ed calves were sacrificed at 1, 4, 8, 18, 28, 38, 48 or 58 days post-treatm ent. Plasma, abomasal and small intestinal fluids and mucosal tissues, bile , faeces, lung and skin samples were collected, extracted, derivatized and analyzed by high performance Liquid chromatography (HPLC) with fluorescence detection to determine IVM and DRM concentrations. IVM and DRM were distri buted to all the tissues and fluids analyzed. Concentrations >0.1 ng/ml (ng /g) were detected between 1 and 48 days post-treatment in all the tissues a nd fluids investigated. At 58 days post-treatment, NM and DRM were detected only in bile and faeces, where large concentrations were excreted, Delayed T-max values for DRM (4 days post-administration) compared to those for IV M (1 day) were observed in the different tissues and fluids. High NM and DR M concentrations were measured in the most important target tissues, includ ing skin. The highest NM and DRM concentrations were measured in abomasal m ucosa and lung tissue. Enhanced availabilities of both IVM (between 45 and 244%) and DRM (20-147%) were obtained in tissues compared to plasma. There was good correlation between concentration profiles of both compounds in pl asma and target tissues (mucosal tissue, skin, and lung). Drug concentratio ns in target tissues remained above 1 ng/g for either 18 (IVM) or 38 (DRM) days post-treatment. The characterization of tissue distribution patterns c ontributes to our understanding of the basis for the broad-spectrum endecto cide activity of avermectin-type compounds. (C) 2000 Elsevier Science B.V. All rights reserved.