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Pharmacokinetic assessment of the monepantel plus oxfendazole combined administration in dairy cows.

Authors :
Ballent, M.
Viviani, P.
Imperiale, F.
Dominguez, P.
Halwachs, S.
Mahnke, H.
Honscha, W.
Lanusse, C.
Virkel, G.
Lifschitz, A.
Source :
Journal of Veterinary Pharmacology & Therapeutics; Apr2018, Vol. 41 Issue 2, p292-300, 9p
Publication Year :
2018

Abstract

Monepantel (MNP) is a novel anthelmintic compound launched into the veterinary pharmaceutical market. MNP is not licenced for use in dairy animals due to the prolonged elimination of its metabolite monepantel sulphone (MNPSO<subscript>2</subscript>) into milk. The goal of this study was to evaluate the presence of potential <italic>in vivo</italic> drug‐drug interactions affecting the pattern of milk excretion after the coadministration of the anthelmintics MNP and oxfendazole (OFZ) to lactating dairy cows. The concentrations of both parent drugs and their metabolites were measured in plasma and milk samples by HPLC. MNPSO<subscript>2</subscript> was the main metabolite recovered from plasma and milk after oral administration of MNP. A high distribution of MNPSO<subscript>2</subscript> into milk was observed. The milk‐to‐plasma ratio (M/P ratio) for this metabolite was equal to 6.75. Conversely, the M/P ratio of OFZ was 1.26. Plasma concentration profiles of MNP and MNPSO<subscript>2</subscript> were not modified in the presence of OFZ. The pattern of MNPSO<subscript>2</subscript> excretion into milk was also unchanged in animals receiving MNP plus OFZ. The percentage of the total administered dose recovered from milk was 0.09 ± 0.04% (MNP) and 2.79 ± 1.54% (MNPSO<subscript>2</subscript>) after the administration of MNP alone and 0.06 ± 0.04% (MNP) and 2.34 ± 1.38% (MNPSO<subscript>2</subscript>) after the combined treatment. The presence of MNP did not alter the plasma and milk disposition kinetics of OFZ. The concentrations of the metabolite fenbendazole sulphone tended to be slightly higher in the coadministered group. Although from a pharmacodynamic point of view the coadministration of MNP and OFZ may be a useful tool, the presence of OFZ did not modify the <italic>in vivo</italic> pharmacokinetic behaviour of MNP and therefore did not result in reduced milk concentrations of MNPSO<subscript>2</subscript>. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01407783
Volume :
41
Issue :
2
Database :
Complementary Index
Journal :
Journal of Veterinary Pharmacology & Therapeutics
Publication Type :
Academic Journal
Accession number :
128312888
Full Text :
https://doi.org/10.1111/jvp.12466