Stability and distribution of macrocyclic lactones in gastrointestinal content in sheep

BALLENT, M.; LIFSCHITZ, A.; SALLOVITZ, J.; IMPERIALE, F.; LANUSSE, C.

San Luis

Congreso; XXXV Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); 2003

The macrocyclic lactones (ML) (ivermectin, moxidectin) are broad-spectrum antiparasitic compounds extensively used in veterinary and human medicine worldwide. A reduced systemic bioavailability of these compounds is obtained after oral administration in ruminants, that affect their efficacy and persistence of anthelmintic activity. The main goal of this study was to investigate the in vitro stability and distribution of ML in gastrointestinal content in sheep. Three Corriedale sheep were slaughtered by captive bolt and samples of ruminal and abomasal content collected, kept at 37 º C and immediately processed for incubation. Aliquots of either ivermectin (IVM) and moxidectin (MXD) in metanol were added to 2 ml to gastrointestinal content to reach a final concentration of 1 nM/ml. The incubation were carried out in a shaking water bath at 37 ºC under anaerobic conditions for 2, 6 and 24 h. After incubation period 1 ml of each sample were centrifuged at 14 rpm to separate the particular and fluid digesta and all samples immediately frozen at –20 ºC until HPLC analysis. IVM and MXD were stable in ruminal and abomasal content after all periods of incubation. There were a singular partition of ML in both gastrointestinal contents. A significantly higher concentration of IVM and MXD (90-99 % of total drug) were obtained in the particular digesta of ruminal and abomasal content. Therefore the partition of ML in the gastrointestinal content influence on the amount and duration in which IVM and MXD are available for gastrointestinal absorption.