Pharmacokinetic processes of Lithium used for food aversion in sheep and goats

Abstract Text: Conditioned taste aversion (CTA) is a useful management tool to control weeds in commercial crops. Lithium chloride (LiCl) is a safe product used in livestock CTA studies to induce aversion to palatable plants. Despite the use of LiCl in numerous studies, there is a lack of information on the pharmacokinetics that accompany different CTA doses in domestic livestock. This information is needed for using selective grazing in practice, and to avoid any possible soil contamination by excreted Li. With this aim, we studied the kinetics of Li elimination in 2 experiments: 1) Murciano-Grandina lactating goats (n = 6) after a single dose of 200 mg LiCl/kg BW; and 2) Manchega dairy sheep, open and dry, after a single dose of 225 mg LiCl/kg BW. For Exp.1, goats were penned in metabolic cages for measuring daily milk yield, water and feed intake. Samples of urine, feces, milk and blood were collected over a period of 168 h. In Exp.2, ewes were maintained as a group in a pen with head lockers, where they were restrained at every sampling time for feces (rectum) and blood (jugular) collection over 192 h. Concentration of Li was measured by graphite furnace Atomic Absorption Spectrometry and data corrected for its basal concentration. Withdrawal period (Wp) was calculated with a statistical tolerance limit of 95% (EMEA/CVMP/036/95). Individual biological half-life (t_1/2) was calculated using PK Solutions computer program (Farrier, 1997). Results showed that plasma Li concentration reached a maximum at 4 h in lactating goats (14.5 ± 0.8 mg Li/L plasma) and 12 h in dry sheep (17.7 ± 0.8 mg Li/L plasma). Values of t_1/2 were 30.9 ± 2.1 and 40.3 ± 3.8 h for sheep and goats, respectively (t = 2.39; DF = 10; P< 0.03). In goats, recovery rate of administered Li was 101.7% at 96 h (urine, 92.4 ± 4.4%; feces, 6.5 ± 1.3%; milk, 2.8 ± 0.4%); however the estimated Wp established in feces was 9 and 11 d for sheep and goats, respectively. In conclusion, Li was fully eliminated in sheep and goats, but needed longer time than reported in other species (i.e., rat and human). LiCl can be used safely to induce CTA for controlling weeds by grazing in organic crops after a waiting period of approximately 1 wk before moving the animals to the crop. Funded by Plan Nacional I+D+I AGL 2010-22178-C02-01.

Keywords: conditioned aversion; small ruminants; lithium chloride