Evaluation of drug-drug interactions in cattle using intestinal explants.

BALLENT M; PEREZ V.; VIRKEL G; LIFSCHITZ A.; LANUSSE C

Buenos Aires

Congreso; Reunión conjunta de Sociedades de Biociencias y XLIX reunion anual de SAFE; 2017

The concurrent administration of drugs is currently used in veterinary medicine. In cattle, the coadministration of anthelmintics may be a useful pharmacological tool to delay the parasite resistance. Different transporter proteins such as P-glycoprotein (P-gp) are involved in the excretion process of anthelmintics. Previous studies corroborated in vivo pharmacokinetic changes obtained after the coadministration of two macrocyclic lactones. The aim of the current trial was to evaluate the modulation of intestinal transport of macrocyclic lactones in cattle using the intestinal explants model. Bovine ileum samples from Aberdeen Angus/Hereford crossbreed steers were obtained from a slaughterhouse located in Tandil area. Immediately following sacrifice, a segment of caudal ileum (30 cm) was opened by the mesenteric border, rinsed with ice-cold 1.15% KCl and immersed in ice-cold Euro-Collins solution. Containers were covered, chilled in ice, and transported to the laboratory within 30?40 min for subsequent procedures. Intestinal explants (19 mm of diameter) were prepared and transferred to 6-well culture plates with 6 ml of Wiliams´ medium E containing abamectin (ABM) alone (0.5 µM) or ABM plus ivermectin (IVM) (1µM). Explants were incubated inside a container with humidified atmosphere of 95% O2:5% CO2 at 37 ºC. Intestinal explants were harvested between 15 and 60 minutes post-incubation and frozen at -20 ºC. ABM concentrations were measured by HPLC with fluorescent detection. The concentrations of ABM in the explants were significantly higher after the coincubation with IVM (P