Phase I biotransformation of albendazole in lancet fluke (Dicrocoelium dendriticum).
Dicroceliosis, a lancet fluke infection, is a frequent parasitosis of small ruminants and the anthelmintic drug albendazole (ABZ) is effective in control of this parasitosis. The aim of our project was to study the metabolism of ABZ and ABZ sulphoxide (ABZ.SO) in lancet fluke. Both invitro (subcellular fractions of fluke homogenates) and exvivo experiments (adult flukes cultivated in medium) were performed for this purpose. ABZ was metabolised invitro by lancet fluke NADPH-dependent enzymes by two oxidative steps (sulphoxidation and sulphonation). The apparent kinetic parameters of these reactions have been determined. In the exvivo experiments, only ABZ sulphoxidation was observed. The stereospecificity in ABZ sulphoxidation invitro was slight, with preferential formation of (+)-ABZ.SO enantiomer. In contrast (-)-ABZ.SO formation predominated in exvivo experiments. Sulphoreduction of ABZ.SO occurred neither invivo nor exvivo. The detection of ABZ oxidative metabolites indicates the presence of drug metabolising oxidases in lancet fluke.
Department of Biochemical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, Hradec Králové CZ-500 05, Czech Republic. viktor.cvilink@faf.cuni.cz
V
V
Cvilink
B
B
Szotáková
V
V
Krízová
J
J
Lamka
L
L
Skálová
D015766:Albendazole / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D000818:Animals; D000871:Anthelmintics / Q000493:pharmacokinetics*; D001711:Biotransformation; D004011:Dicrocoeliasis / Q000469:parasitology / Q000662:veterinary*; D004013:Dicrocoelium / Q000378:metabolism*; D005260:Female; D008107:Liver Diseases / Q000469:parasitology / Q000662:veterinary*; D015203:Reproducibility of Results; D012756:Sheep; D012757:Sheep Diseases / Q000469:parasitology*
D000871:Anthelmintics; D015766:Albendazole; C027186:albendazole sulfoxide