Pharmacokinetics and efficacy of triclabendazole in goats with induced fascioliasis

Abstract

The pharmacokinetics of triclabendazole were evaluated in normal goats and in goats artificially infected with Fasciola hepatica. Triclabendazole and its metabolites were determined using a novel high performance liquid chromatographic method with fluorimetric detection after solid-phase extraction. In normal goats triclabendazole given orally was metabolized rapidly to its sulphoxide and sulphone derivatives. The maximum plasma concentrations for the sulphoxide and sulphone were similar ranging from 9 to 19 micrograms/ml and these were attained at an average 12.8 and 25.6 h, respectively, after administration. Both metabolites were eliminated slowly from plasma with elimination half-lives of 22.4 h for the sulphoxide and 19.4 h for the sulphone. They persisted at measurable concentrations in plasma for up to seven days. In milk, the two metabolites occurred in low concentrations and none of them was detectable (sulphoxide less than 0.04 microgram/ml, sulphone less than 0.02 microgram/ml) after seven days. The pharmacokinetic behaviour of triclabendazole was not altered in animals with fascioliasis. Efficacy of the drug against immature (six-week) F. hepatica was 100%.

Effect of Fascioliasis on the pharmacokinetic parameters of triclabendazole in human subjects

“…This finding is in agreement with a previous study conducted in both normal and infected goats and reported that the pharmacokinetic behaviour of TCBZ was not altered in fascioliasis [20]. This may not be surprising since the liver has considerable reserves with respect to drug metabolism and significant pharmacokinetic alterations for most drugs are only seen if the liver is severely damaged [21].…”

“…The absence of TCBZ and presence of its sulfoxide metabolite in plasma shortly after administration could be attributed to the strong first pass hepatic metabolism of TCBZ. Same results are reported in similar works done previously not only on animals [20] but also on human [2,3].…”

Economic and Production Consequences of Liver Fluke Disease in Double‐Muscled Fattening Cattle

“…O u r purpose was therefore not to find a drug which could be a candidate for programmes to control the liver fluke parasite. However, it is important to quote that the reduction in the fluke burdens and the efficiency in combatting both immature and mature stages of Fusciolu hepatica are higher with other drugs such as triclabendazole (BORAY and HAPPICH, 1968;KINABO and BOGAN, 1988;FUHUI, 1989;QURESHI et al, 1989) and diamphenetide (HARPENIST, 1973). Further studies might be done in order to investigate if such drugs characterized by an higher flukicidal potency but 208 GENICOT, MOULIGNEAU and LEKEUX also by higher prices induce a significantly higher improvement of daily body gains in Belgian double-muscled fattening bulls infected with Fasciofa hepatica.…”

Pharmacokinetic disposition of triclabendazole in cattle and sheep; discrimination of the order and the rate of the absorption process of its active metabolite triclabendazole sulfoxide

“…Triclabendazole (TCBZ; 6-chloro-5-(2, 3-dichlorophenoxy)-2-methylthiobenzimidazole) is a member of the benzimidazole (BZD) group of anthelmintics and is highly effective against mature and immature stages of Fasciola hepatica and Fasciola gigantica in all ruminant species (Boray 1983;Turner et al 1984;Bennett and Köhler 1987;Kinabo andBogan 1988, Mottier et al 2004).…”