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The metabolic fate of ivermectin in host (Ovis aries) and parasite (Haemonchus contortus)

Published online by Cambridge University Press:  22 October 2012

IVAN VOKŘÁL ,
VERONIKA JEDLIČKOVÁ ,
ROBERT JIRÁSKO ,
LUCIE STUCHLÍKOVÁ ,
HANA BÁRTÍKOVÁ ,
LENKA SKÁLOVÁ ,
JIŘÍ LAMKA ,
MICHAL HOLČAPEK  and
BARBORA SZOTÁKOVÁ
IVAN VOKŘÁL
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
VERONIKA JEDLIČKOVÁ
Affiliation:
Faculty of Chemical Technology, University of Pardubice, Studentská 573, CZ-53210 Pardubice, Czech Republic
ROBERT JIRÁSKO
Affiliation:
Faculty of Chemical Technology, University of Pardubice, Studentská 573, CZ-53210 Pardubice, Czech Republic
LUCIE STUCHLÍKOVÁ
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
HANA BÁRTÍKOVÁ
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
LENKA SKÁLOVÁ
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
JIŘÍ LAMKA
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
MICHAL HOLČAPEK
Affiliation:
Faculty of Chemical Technology, University of Pardubice, Studentská 573, CZ-53210 Pardubice, Czech Republic
BARBORA SZOTÁKOVÁ*
Affiliation:
Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic
*
*Corresponding author: Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic. Tel: +420 495 067 324. Fax: +420 495 067 168. E-mail: [email protected]
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Summary

Ivermectin (IVE), one of the most important anthelmintics, is often used in the treatment of haemonchosis in ruminants. The objective of our work was (1) to find and identify phase I and II metabolites of IVE formed by the Barber's pole worm (Haemonchus contortus), and (2) to compare IVE metabolites in helminths with IVE biotransformation in sheep (Ovis aries) as host species. Ultrahigh-performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS) was used for this purpose. During in vitro incubations, microsomes (from adult worms or from ovine liver) and a primary culture of ovine hepatocytes were incubated with IVE. In the ex vivo study, living H. contortus adults were incubated in the presence of 1 μM IVE for 24 h. The results showed that the H. contortus enzymatic system is not able to metabolize IVE. On the other hand, 7 different phase I as well as 9 phase II IVE metabolites were detected in ovine samples using UHPLC/MS/MS analyses. Most of these metabolites have not been described before. Haemonchus contortus is not able to deactivate IVE through biotransformation; therefore, biotransformation does not contribute to the development of IVE-resistance in the Barber's pole worm.

Keywords

ivermectinHaemonchus contortusbiotransformationUHPLC/MS/MS
Type
Research Article
Information
Parasitology , Volume 140 , Issue 3 , March 2013 , pp. 361 - 367
Copyright
Copyright © Cambridge University Press 2012

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