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Effects of dietary sodium butyrate on hepatic biotransformation and pharmacokinetics of erythromycin in chickens
Author(s) -
Csikó G.,
Nagy G.,
Mátis G.,
Neogrády Z.,
Kulcsár A.,
Jerzsele Á.,
Szekér K.,
Gálfi P.
Publication year - 2014
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12109
Subject(s) - butyrate , in vivo , sodium butyrate , pharmacokinetics , erythromycin , cytochrome p450 , pharmacology , chemistry , in vitro , biology , biochemistry , metabolism , antibiotics , gene , microbiology and biotechnology , fermentation
Butyrate, a commonly applied feed additive in poultry nutrition, can modify the expression of certain genes, including those encoding cytochrome P 450 (CYP) enzymes. In comparative in vitro and in vivo experiments, the effect of butyrate on hepatic CYP genes was examined in primary cultures of chicken hepatocytes and in liver samples of chickens collected from animals that had been given butyrate as a feed additive. Moreover, the effect of butyrate on the biotransformation of erythromycin, a marker substance for the activity of enzymes of the CYP 3 A family, was investigated in vitro and in vivo . Butyrate increased the expression of the avian‐specific CYP 2 H 1 both in vitro and in vivo . In contrast, the avian CYP 3 A 37 expression was decreased in hepatocytes following butyrate exposure, but not in the in vivo model. CYP 1 A was suppressed by butyrate in the in vitro experiments, and overexpressed in vivo in butyrate‐fed animals. The concomitant incubation of hepatocytes with butyrate and erythromycin led to an increased CYP 2 H 1 expression and a less pronounced inhibition of CYP 3A37. In in vivo pharmacokinetic experiments, butyrate‐fed animals given a single i.m. injection of erythromycin, a slower absorption phase (longer T half‐abs and delayed T max ) but a rapid elimination phase of this marker substrate was observed. Although these measurable differences were detected in the pharmacokinetics of erythromycin, it is unlikely that a concomitant application of sodium butyrate with erythromycin or other CYP substrates will cause clinically significant feed‐drug interaction in chickens.