title: Uptake of benzimidazoles by Trichuris suis in vivo in pigs.
abstract: It is recognized that the clinical efficacy of single dose benzimidazoles (BZs) against the nematode, Trichuris suis of pigs and the closely related Trichuris trichiura in humans is only poor to moderate. Recent in vitro studies have indicated that a low uptake of fenbendazole (FBZ) in T. suis may be responsible for its poor efficacy. The aim of this study was to investigate this hypothesis by measuring the concentrations of FBZ and its metabolites, oxfendazole (OXF) and FBZ sulphone (FBZSO2), in T. suis isolated from FBZ treated pigs and in plasma of the pigs. The highest concentration of FBZ measured in T. suis was 66.6 pmol/mg dry worm tissue which was approximately half of what was measured in a previous in vitro study. The correlation between drug concentrations in plasma and in T. suis worms was highly positive for OXF (r = 0.93, P = 0.0007) and FBZSO2 (r = 0.85, P = 0.007), but no correlation was found for FBZ. This study shows that the low uptake of FBZ observed for T. suis in vitro, also takes place in vivo. The high and significant correlations between OXF and FBZSO2 concentrations in plasma of the pigs and T. suis (and the lack of this correlation for FBZ) suggests that the metabolites reach the worms via the blood-enterocyte interface while FBZ primarily reaches the worms via the intestinal lumen of the host.
authors: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlaegevej 100, DK-1870 Frederiksberg C, Denmark.
authors: Tina V A
authors: TV
authors: Hansen
authors: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlaegevej 100, DK-1870 Frederiksberg C, Denmark.
authors: Christian
authors: C
authors: Friis
authors: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlaegevej 100, DK-1870 Frederiksberg C, Denmark.
authors: Peter
authors: P
authors: Nejsum
authors: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlaegevej 100, DK-1870 Frederiksberg C, Denmark.
authors: Annette
authors: A
authors: Olsen
authors: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlaegevej 100, DK-1870 Frederiksberg C, Denmark.
authors: Stig Milan
authors: SM
authors: Thamsborg
keywords: Benzimidazole; Drug-uptake; Treatment efficacy; Trichuris suis; Trichuris trichiura