title: Effect of early treatment with rafoxanide on antipyrine clearance in sheep infected with Fasciola hepatica.
abstract: 1. The effect of the salicylanilide compound rafoxanide against immature stages of Fasciola hepatica was investigated in sheep using a series of antipyrine clearance tests and measuring glutamate dehydrogenase and gamma-glutamyl transferase activities in plasma. 2. Three animal groups were used. In two groups, sheep were infected with 200 metacercariae each. Four weeks after infection one of the two groups was treated with rafoxanide and the other was left untreated. The third group was unparasitized and also received rafoxanide. 3. Infection was confirmed by post-mortem examination of the livers of infected sheep. Infection did not alter the plasma disposition of rafoxanide. 4. The efficacy of rafoxanide, as assessed by the reduction in the number of adult flukes in treated animals compared with controls, was 85%. 5. Glutamate dehydrogenase activity fell dramatically 2 weeks after treatment but increased again at 12 weeks post-infection in the infected rafoxanide-treated group. 6. Antipyrine clearance decreased between 8 and 14 weeks post-infection in untreated sheep. In the infected rafoxanide-treated group plasma clearance of antipyrine remained unchanged until 10 weeks after rafoxanide administration when it decreased from the preinfection value of 5.09 to 3.90 ml.kg/min. Rafoxanide did not affect antipyrine disposition in uninfected sheep. 7. It was concluded that rafoxanide had an incomplete anthelmintic effect against immature stages of Fasciola hepatica, and that surviving parasites caused delayed liver damage which was reflected in an elevation in glutamate dehydrogenase activity and decreased plasma clearance of antipyrine.
authors.affiliation: Department of Veterinary Pharmacology, University of Glasgow Veterinary School, Bearsden, UK.
authors.forename: H A
authors.initials: HA
authors.lastname: Benchaoui
authors.forename: Q A
authors.initials: QA
authors.lastname: McKellar
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000493:pharmacokinetics*; D005210:Fasciola hepatica / Q000187:drug effects*; D005211:Fascioliasis / Q000378:metabolism / Q000469:parasitology / Q000662:veterinary*; D005969:Glutamate Dehydrogenase / Q000097:blood; D008099:Liver / Q000469:parasitology; D011888:Rafoxanide / Q000494:pharmacology*; D012756:Sheep; D012757:Sheep Diseases / Q000378:metabolism* / Q000469:parasitology; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D011888:Rafoxanide; D005969:Glutamate Dehydrogenase; D005723:gamma-Glutamyltransferase; D000983:Antipyrine