Effect of administration route and dose escalation on plasma and intestinal concentrations of enrofloxacin and ciprofloxacin in broiler chickens

Abstract

BackgroundThe (mis)use of fluoroquinolones in the fowl industry has led to an alarming incidence of fluoroquinolone resistance in pathogenic as well as commensal bacteria. Next to simply reducing antimicrobial consumption, optimizing dosage regimens can be regarded as a suitable strategy to reduce antimicrobial resistance development without jeopardizing therapy efficacy and outcome. A first step in order to limit antimicrobial resistance is to assess the exposure of the intestinal microbiota to enrofloxacin after different treatment strategies. Therefore, a study was conducted in broiler chickens to assess the effect of route of administration (oral versus intramuscular) and dose escalation (10 and 50 mg/kg body weight) on plasma and intestinal concentrations of enrofloxacin and its main metabolite ciprofloxacin after treatment with enrofloxacin once daily for five consecutive days. Four different parts of the intestinal tract were sampled: ileum, cecum, colon and cloaca. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to quantify both analytes in plasma and intestinal content. Sample preparation prior to LC-MS/MS analysis consisted of extraction with ethyl acetate. For intestinal content samples PBS buffer was added before extraction. The supernatant was evaporated to dryness and resuspended in water prior to analysis.ResultsThe results in plasma and intestinal content demonstrated that biotransformation of enro- to ciprofloxacin in broiler chickens is limited. In general, the intestinal microbiota in cecum and colon is exposed to significant levels of enrofloxacin after conventional treatment (21–130 μg/g). A clear increase of intestinal concentrations was demonstrated after administration of a five-fold higher dose (31–454 μg/g). After intramuscular administration, intestinal concentrations were comparable, except for the higher levels in cloaca due to the complete bioavailability and urinary excretion.ConclusionsThe intestinal microbiota is exposed to high levels of the antimicrobial, after oral as well as parenteral therapy. Furthermore, a dose and time dependent correlation was observed. The impact of the detected intestinal levels on resistance selection in the intestinal microbiota has to be further investigated.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-014-0289-1) contains supplementary material, which is available to authorized users.

Pharmacokinetic–Pharmacodynamic Modeling of Enrofloxacin Against Escherichia coli in Broilers

“…Moraru et al ( 31 ) detected enrofloxacin concentrations in excreta samples ranged between 40.5 and 50.7 μg/g after 3 days orally treatment with 10 mg enrofloxacin/kg BW. Devreese et al ( 26 ) found enrofloxacin concentrations in cloacal samples ranged between 20.1 and 55.7 μg/g after orally treatment of 10 mg enrofloxacin/kg BW. In this study, we found the enrofloxacin concentrations in the intestinal contents were significantly less than previously reported concentrations that maybe due to sample and dosage differences.…”

“…The metabolism of enrofloxacin to ciprofloxacin in broilers is limited to 5 and 10% ( 23 , 24 ). There is some research on the PK of enrofloxacin in intestinal contents ( 25 , 26 ), but limited data are available regarding the PK/PD in broiler intestinal contents.…”

The impact of ginsenosides on cognitive deficits in experimental animal studies of Alzheimer’s disease: a systematic review

“…First, the effect size was higher in rat studies than in mouse studies, which suggests that different species may react differently to ginsenoside. Second, the route of administration and dosage of ginsenoside also affected the outcome [ 42 ]. The protective effect on acquisition memory was better with doses of 30 mg or higher (although not significantly) and the protective effect on retention memory was better with doses of 10 mg.…”

Not All Antibiotic Use Practices in Food-Animal Agriculture Afford the Same Risk

“…From a risk perspective, greater attention to oral administration practices may be more useful, although this should be confirmed empirically for different antibiotics and animals. For example, Devreese et al (2014) found similar concentrations of enrofloxacin in the cecum and colon of broiler chickens that were treated orally or by intramuscular injection. Unexpectedly higher concentrations were present in the cloaca after systemic injection compared with oral administration.…”