Phase I biotransformation of albendazole in lancet fluke (Dicrocoelium dendriticum)

被引：21

作者：

Cvilink, V. ^{[1
]}

Szotakova, B. ^{[1
]}

Krizova, V. ^{[1
]}

Lamka, J. ^{[1
]}

Skalova, L. ^{[1
]}

机构：

[1] Charles Univ Prague, Dept Biochem Sci, Fac Pharm, CZ-50005 Hradec Kralove, Czech Republic

来源：

RESEARCH IN VETERINARY SCIENCE | 2009年 / 86卷 / 01期

关键词：

Drug metabolism; Anthelmintics; Dicrocoeliosis; Stereospecificity; HAEMONCHUS-CONTORTUS; HELMINTH-PARASITES; FASCIOLA-HEPATICA; COMPARATIVE METABOLISM; SULFOXIDE; DRUG; SHEEP; CYTOCHROME-P450; RESISTANT; MECHANISMS;

D O I：

10.1016/j.rvsc.2008.05.006

中图分类号：

S85 [动物医学（兽医学）];

学科分类号：

090604 [动物药学];

摘要：

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 in vitro (subcellular fractions of fluke homogenates) and ex vivo experiments (adult flukes cultivated in medium) were performed for this purpose. ABZ was metabolised in vitro 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 ex vivo experiments, only ABZ sulphoxidation was observed. The stereospecificity in ABZ sulphoxidation in vitro was slight, with preferential formation of (+)-ABZ.SO enantiomer. In contrast (-)-ABZ.SO formation predominated in ex vivo experiments. Sulphoreduction of ABZ.SO occurred neither in vivo nor ex vivo. The detection of ABZ oxidative metabolites indicates the presence of drug metabolising oxidases in lancet fluke. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：49 / 55

页数：7

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