In vitro and in vivo assessment of the benzydamine-mediated interference with the hepatic S-oxidation of the anthelmintic albendazole in sheep

VIRKEL G.; LIFSCHITZ A.; SALLOVITZ J.; MATÉ L.; LANUSSE C.

JOURNAL OF SMALL RUMINANT RESEARCH

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2014 vol. 120 p. 142 - 149

0921-4488

Objectives The aim of this research was to investigate the influence of benzydamine (BZ) on the hepatic metabolism of the anthelmintic albendazole (ABZ) in sheep. Methods The enantioselective ABZ S-oxidation was assessed by the amount of its (-) and (+) ABZ-sulphoxide (ABZSO) enantiomers formed in sheep liver microsomes (in vitro work). A cross over design was employed for the pharmacokinetic trial (in vivo assay). Corriedale x Merino cross-breed lambs (n=8) received albendazole (5 mg/kg, intra-ruminal route) or albendazole (5 mg/kg) plus BZ (8 mg/kg, i.m., two doses 4 h apart). Incubated and plasma samples were analysed by HPLC. Key findings Benzydamine IC50s for the production of total ABZSO and (+)ABZSO were 71.0 ± 8.1 and 62.6 ± 8.1 µM, respectively. A strong inhibitory potency of BZ over the flavin-monooxygenase (FMO)-dependent production of (+)ABZSO compared to the cytochrome P450 (CYP)-mediated production of (-)ABZSO was also observed. Significantly higher (p