Effects of ionophores on liver CYP1A and 3A in male broilers

Drug-drug interactions (DDIs) may adversely affect the prevention and cure of diseases. The effects of three polyether ionophore antibiotics, salinomycin (SAL), monensin (MON), and maduramycin (MAD) on the pharmacokinetics of florfenicol (FFC) were investigated in broilers. The chickens were fed rations with or without SAL (60 mg/kg feeds), MON (120 mg/kg feeds), or MAD (5 mg/kg feeds) for 14 consecutive days. FFC was given to the chickens either intravenously (i.v.) or orally (p.o.) at a single dose of 30 mg/kg body weight. Blood samples were taken from each chicken at 0-24 h postadministration of FFC. The plasma concentration of FFC was detected by high-performance liquid chromatography. The plasma concentration of FFC decreased with i.v. or p.o. co-administration of SAL, MON, or MAD in broilers, implying occurrence of DDIs during the co-administration of FFC with these ionophores. Our findings suggest that more attention should be given to the use of FFC to treat bacterial infections in chickens supplemented with polyether ionophore antibiotics.

Section: Discussionmentioning

confidence: 99%

“…As reported by Zhang et al . (), we added polyether ionophores to feed at veterinary clinical recommended dosages for 14 consecutive days to induce metabolic enzymes of chickens in this study. To estimate the levels of the polyether ionophores, we presumed that the feed intake of each chicken was a definite value.…”

Section: Discussionmentioning

confidence: 99%

Effect of three polyether ionophores on pharmacokinetics of florfenicol in male broilers

Wang

Chen

et al. 2012

“…The primers used for CYP3A37 amplification were adopted from Zhang et al . and were as follows: CYP3A37 forward, 5′‐CGAATCCCAGAAATCAGA–3′ and CYP3A37 reverse, 5′‐AGCCAGGTAACCAAGTGT‐3′ (GenBank ID: NM 001001751.1) (Zhang et al ., ). The annealing temperature was set at 60 °C for the primers.…”

Section: Methodsmentioning

confidence: 97%

“…Absolute quantification was carried out using the Applied Biosystems 7 500 Fast Real-Time PCR System (Applied Biosystems, Foster City, CA). The primers used for CYP3A37 amplification were adopted from Zhang et al and were as follows: CYP3A37 forward, 5′-CGAATCCCAGAAATCAGA-3′ and CYP3A37 reverse, 5′-AGCCAGGTAACCAAGTGT-3′ (GenBank ID: NM 001001751.1) (Zhang et al, 2010). The annealing temperature was set at 60°C for the primers.…”

Section: Microsomal Preparation For Cyp3a Activity Measurementsmentioning

confidence: 99%

Hepatic and intestinal CYP3A expression and activity in broilers

Osselaere

Bock

Eeckhaut

et al. 2013

Cytochrome P450 is involved in drug metabolism. Subfamily CYP3A shows a degree of similarity across different animal species. However, little information is available about its expression and activity in broiler chickens. A RT-PCR method was developed for the quantification of CYP3A37 expression in the liver and small intestine of broilers. A higher expression in the jejunum was observed compared with that in the ileum. In the liver, a significantly lower expression compared with that in the jejunum was noticed. Thus, the role of the small bowel in drug metabolism cannot be neglected in broilers. CYP3A activity was studied in vitro using midazolam as a substrate. Two protocols for the preparation of intestinal microsomes were compared. Mincing of the tissues before ultracentrifugation seemed to be more appropriate than a protocol based on ethylenediaminetetra-acetic acid separation. CYP3A activity revealed to be the highest in the duodenum with a decreasing trend towards the ileum. Activity in liver was comparable to duodenal activity.

“…The chicken CYP3A37 gene is considered to be ortholog to the human CYP3A4 (Ourlin et al ., ). CYP3A isoforms play a pivotal role in the metabolism of about 50% of all therapeutics in human medicine including various antimicrobials, sedatives, dysrhythmics, calcium channel antagonists and protease inhibitors and antihistamines (Zhang et al ., ). Genes of the CYP2H1 (homolog to rodent CYP2B) and CYP3A enzymes can be induced not only by phenobarbital but also by dexamethasone (Handschin & Meyer, ).…”

Section: Introductionmentioning

confidence: 97%

Effects of dietary sodium butyrate on hepatic biotransformation and pharmacokinetics of erythromycin in chickens

Csikó

Nagy

Mátis

et al. 2014

Butyrate, a commonly applied feed additive in poultry nutrition, can modify the expression of certain genes, including those encoding cytochrome P450 (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 CYP3A family, was investigated in vitro and in vivo. Butyrate increased the expression of the avian-specific CYP2H1 both in vitro and in vivo. In contrast, the avian CYP3A37 expression was decreased in hepatocytes following butyrate exposure, but not in the in vivo model. CYP1A 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 CYP2H1 expression and a less pronounced inhibition of CYP3A37. 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.