The Metabolism and Fate of Closantel (Flukiver) in Sheep and Cattle

Abstract

Closantel was reasonably well absorbed in sheep and cattle. After oral (10 mg/kg) or parenteral (5 mg/kg) administration, similar peak times (8-48 h) and peak plasma levels (45-55 micrograms/mL) are observed. Plasma level-time curves are superimposable for either route and increase linearly with the dose. The elimination half-life of closantel is 2 to 3 weeks. The relative bioavailability of 50% of oral closantel can partly be explained by incomplete absorption. Experiments in sheep with 14C-closantel revealed that the plasma radioactivity is almost exclusively due to the unmetabolized drug, metabolites accounting for less than 2%. At least 80% of the dose was excreted with the feces over the investigational period of 8 weeks, and less than 0.5% with the urine. Closantel was only poorly metabolized. Over 90% of the fecal radioactivity was due to the parent compound. Two monoiodoclosantel isomers were the only fecal metabolites detected with radio-HPLC. The distribution of closantel to tissues was limited by its high protein binding. Closantel bound strongly (greater than 99.9%) and almost exclusively to plasma albumin. Accordingly, tissue concentrations were many times lower than the corresponding plasma levels. Residual radioactivity in sheep in all tissues but liver was entirely due to closantel. About 30% to 40% of the liver radioactivity could be attributed to monoiodoclosantel. In both sheep and cattle, residual tissue concentrations decline parallel to the plasma concentrations. Consequently, the plasma kinetics of closantel reliably reflect its depletion from tissues. Independently of the dosing scheme and route of administration, the maximum daily intake by the consumer was always below the acceptable daily intake within 4 weeks after the last dose.

Efficacy of Closantel 5% against Cattle Gastrointestinal Parasites

“…The pharmacokinetics of ivermectin have been extensively reported in ruminants (Degroodt et al, 1994;Fairweather and Boray, 1999;EAVPT, 1986;Michiels et al, 1987), as have those of closantel (Vercruysse and Rew, 2002;Lanusse and Prichard, 1993;Montenegro et al, 2003;Lanusse et al, 1997;Mohammed-Ali and Bogan, 1987;Edem and Usoh, 2009;Akinnuga et al, 2010). Recently a novel product combining closantel and ivermectin in a single formulation has been developed and licensed for use in cattle.…”

Alterações oftálmicas associadas à intoxicação experimental por closantel em caprinos

“…cianometil]-2-metilfenol}-2-hidroxi 3,5-diiodo benzamida) é um anti-helmíntico usado em bovinos e pequenos ruminantes, com eficácia contra Haemonchus contortus, larvas de Oestrus ovis, Fasciola hepatica e outros parasitas hematófagos (Michiels et al, 1987;Hennessy et al, 1993). Pertence à classe dos salicilanilídeos halogenados e age por via oral e intramuscular (Guerrero, 1984;Michiels et al, 1987).…”

“…Pertence à classe dos salicilanilídeos halogenados e age por via oral e intramuscular (Guerrero, 1984;Michiels et al, 1987). Quando o sangue é sugado pelos parasitas, o fármaco, que se encontra ligado às proteínas plasmáticas, age interferindo na síntese de ATP pela mitocôndria das células do parasita, por meio do desacoplamento da fosforilação oxidativa (Van Den Bossche et al, 1979;Michiels et al, 1987).…”

Screening of closantel and rafoxanide in animal muscles by HPLC with fluorescence detection and confirmation using MS

“…) are broad-spectrum antiparasitic agents belonging to salicylanilide antibiotics which are commonly used to treat and control fascioliasis in sheep and cattle [1]. Closantel and rafoxanide bond strongly to plasma proteins.…”