Uptake of benzimidazoles by Trichuris suis in vivo in pigs
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Uptake of benzimidazoles by Trichuris suis in vivo in pigs. / Hansen, Tina Vicky Alstrup; Friis, Christian; Nejsum, Peter; Olsen, Annette; Thamsborg, Stig Milan.
In: International Journal for Parasitology: Drugs and Drug Resistance, Vol. 4, No. 2, 2014, p. 112-117.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Uptake of benzimidazoles by Trichuris suis in vivo in pigs
AU - Hansen, Tina Vicky Alstrup
AU - Friis, Christian
AU - Nejsum, Peter
AU - Olsen, Annette
AU - Thamsborg, Stig Milan
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Faculty of Health and Medical Sciences
KW - Trichuris trichiura
KW - Trichuris suis
KW - Benzimidazole
KW - Drug-uptake
KW - Treatment efficacy
U2 - 10.1016/j.ijpddr.2014.03.003
DO - 10.1016/j.ijpddr.2014.03.003
M3 - Journal article
C2 - 25057460
VL - 4
SP - 112
EP - 117
JO - International Journal for Parasitology
JF - International Journal for Parasitology
SN - 0020-7519
IS - 2
ER -
ID: 122666894