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

G. VIRKEL, A. LIFSCHITZ, J. SALLOVITZ, L. MATÉ, C. FARÍAS, C. LANUSSE.

JOURNAL OF SMALL RUMINANT RESEARCH

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2014 vol. 120 p. 140 - 149

0921-4488

tThe aim of this research was to investigate the influence of benzydamine (BZ) on thein vitro and in vivo hepatic metabolism of the anthelmintic albendazole (ABZ) in sheep.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). In thein vivo trial, lambs received ABZ (5 mg/kg, intra-ruminal route) or ABZ (5 mg/kg) plus BZ(8 mg/kg, i.m., two doses 4 h apart). Incubated and plasma samples were analysed by HPLC.In vitro, BZ IC50s (the concentrations that produced a 50% decrease in ABZ S-oxidation) forthe production of total ABZSO and (+)ABZSO were 71.0 ± 8.1 and 62.6 ± 8.1 M, respectively.BZ showed a strong inhibitory potency over the flavin-monooxygenase (FMO)-dependentproduction of (+)ABZSO compared to the cytochrome P450 (CYP)-mediated productionof (−)ABZSO. In vivo, co-administration of BZ with ABZ did not change the pharma-cokinetic parameters of ABZSO and ABZSO2with the exception of significantly higher(p < 0.01) formation half-lives (t1/2for) for (−)ABZSO (3.24 ± 1.03 h vs. 6.19 ± 2.18 h) and(+)ABZSO (3.87 ± 1.20 h vs. 7.21 ± 2.46 h). BZ inhibited the hepatic FMO and CYP-dependentS-oxidation of ABZ in vitro. However, the metabolic interaction between ABZ and BZ wasnot observed in the in vivo pharmacokinetic trial. Hence, further work using a differentdosing scheme or pharmaco-technical preparation of BZ may be required to observe in vivothe metabolic interference clearly shown under in vitro conditions.