INVESTIGADORES
VIRKEL Guillermo Leon
artículos
Título:
In vitro and in vivo assessment of the benzydamine-mediated interference with the hepatic S-oxidation of the anthelmintic albendazole in sheep
Autor/es:
VIRKEL, G.; LIFSCHITZ, A.; SALLOVITZ, J.; MATÉ, L.; FARÍAS, C.; LANUSSE, C.
Revista:
JOURNAL OF SMALL RUMINANT RESEARCH
Editorial:
ELSEVIER SCIENCE BV
Referencias:
Lugar: Amsterdam; Año: 2014 vol. 120 p. 142 - 149
ISSN:
0921-4488
Resumen:
The aim of this research was to investigate the influence of benzydamine
(BZ) on the in 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 the in
vivo trial, lambs received ABZ (5mg/kg, intra-ruminal route) or ABZ
(5mg/kg) plus BZ (8mg/kg, i.m., two doses 4h apart). Incubated and
plasma samples were analysed by HPLC. In vitro, BZ IC50s (the
concentrations that produced a 50% decrease in ABZ S-oxidation) for the
production of total ABZSO and (+)ABZSO were 71.0±8.1 and 62.6±8.1μM,
respectively. BZ showed a strong inhibitory potency over the
flavin-monooxygenase (FMO)-dependent production of (+)ABZSO compared to
the cytochrome P450 (CYP)-mediated production of (-)ABZSO. In vivo,
co-administration of BZ with ABZ did not change the pharmacokinetic
parameters of ABZSO and ABZSO2 with the exception of significantly higher (p<0.01) formation half-lives (t1/2for)
for (-)ABZSO (3.24±1.03h vs. 6.19±2.18h) and (+)ABZSO (3.87±1.20h vs.
7.21±2.46h). BZ inhibited the hepatic FMO and CYP-dependent S-oxidation
of ABZ in vitro. However, the metabolic interaction between ABZ and BZ
was not observed in the in vivo pharmacokinetic trial. Hence, further
work using a different dosing scheme or pharmaco-technical preparation
of BZ may be required to observe in vivo the metabolic interference
clearly shown under in vitro conditions.