Effect of early treatment with rafoxanide on antipyrine clearance in sheep infected with Fasciola hepatica

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.Peer reviewe

Fenbendazole pharmacokinetics, metabolism, and potentiation in horses

The present study was designed to describe the pharmacokinetics and fecal excretion of fenbendazole (FBZ) and fenbendazole sulphoxide (FBZSO) and their metabolites in horses, to investigate the effects which concurrent feeding has on the absorption and pharmacokinetics of FBZ, and to determine the effect of coadministration of the metabolic inhibitor piperonyl-butoxide on the in vivo pharmacokinetics and in vitro liver microsomal metabolism of sulfide and sulfoxide benzimidazoles. The effect of piperonyl-butoxide on the enantiomeric genesis of the sulfoxide moiety was also investigated. Following administration of FBZSO and FBZ, the fenbendazole sulphone metabolite predominated in plasma, and the C-max and area under the plasma curve (AUC) values for each moiety were larger (P 4:1 to 1:1. It is concluded that in horses efficacy of FBZSO and FBZ could be improved by administration to unfed animals and coadministration with piperonyl-butoxide.Peer reviewe

The absorption, distribution and elimination of anthelmintic drugs : the role of pharmacokinetics

Peer reviewe