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

Devreese M, Antonissen G, De Baere S, De Backer P, Croubels S - BMC Vet. Res. (2014)

Bottom Line: 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.The 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium. mathias.devreese@ugent.be.

ABSTRACT

Background: The (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.

Results: The 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.

Conclusions: The 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.

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Plasma concentrations (average + SD) of enro- (A) and ciprofloxacin (B) 2, 4 and 100 hours after the first oral (PO) or intramuscular (IM) administration of 10 or 50 mg enrofloxacin/kg body weight to broiler chickens given during 5 consecutive days (n = 8). Values from the different treatment strategies with a different superscript within one time point, for the same compound ((A) or (B)), are statistically different at p < 0.05. The inserts show the chemical structure of enro- (A) and ciprofloxacin (B).
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Fig1: Plasma concentrations (average + SD) of enro- (A) and ciprofloxacin (B) 2, 4 and 100 hours after the first oral (PO) or intramuscular (IM) administration of 10 or 50 mg enrofloxacin/kg body weight to broiler chickens given during 5 consecutive days (n = 8). Values from the different treatment strategies with a different superscript within one time point, for the same compound ((A) or (B)), are statistically different at p < 0.05. The inserts show the chemical structure of enro- (A) and ciprofloxacin (B).

Mentions: The plasma concentrations of enro- and ciprofloxacin after oral or intramuscular administration are presented in Figure 1. Values present the mean (+ standard deviation, SD) of the 8 birds/group. Biotransformation of enro- to ciprofloxacin in broiler chickens is limited, as can be concluded from the concentration ranges measured for enrofloxacin: 1.66 to 14.04 μg/mL compared to ciprofloxacin: 0.08 to 0.65 μg/mL. The time of sampling, namely 2 or 4 h after first administration or 4 h after last administration (100 h), had a limited influence of the plasma levels of enro- and ciprofloxacin. However, dose escalation, from 10 mg/kg BW to 50 mg/kg BW, led to linearly increased plasma concentrations. At a dose of 10 mg/kg, the administration route (oral, PO, versus intramuscular, IM) altered the mean plasma concentrations only at 100 h (PO: 2.64 ± 0.42 μg/mL, IM: 1.66 ± 0.17 μg/mL) but not at 2 (PO: 3.02 ± 0.77 μg/mL, IM: 4.41 ± 1.26 μg/mL) and 4 h (PO: 2.69 ± 0.38 μg/mL, IM: 2.66 ± 0.31 μg/mL). In contrast, at the elevated dosage of 50 mg/kg, plasma levels at 2 (PO: 9.27 ± 1.15 μg/mL, IM: 14.04 ± 1.93 μg/mL) and 4 h (PO: 6.63 ± 1.12 μg/mL, IM: 12.66 ± 3.53 μg/mL) post administration were higher after parenteral administration, but not at 100 h (PO: 10.32 ± 1.62 μg/mL, IM: 8.54 ± 4.41 μg/mL).Figure 1


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

Devreese M, Antonissen G, De Baere S, De Backer P, Croubels S - BMC Vet. Res. (2014)

Plasma concentrations (average + SD) of enro- (A) and ciprofloxacin (B) 2, 4 and 100 hours after the first oral (PO) or intramuscular (IM) administration of 10 or 50 mg enrofloxacin/kg body weight to broiler chickens given during 5 consecutive days (n = 8). Values from the different treatment strategies with a different superscript within one time point, for the same compound ((A) or (B)), are statistically different at p < 0.05. The inserts show the chemical structure of enro- (A) and ciprofloxacin (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4260181&req=5

Fig1: Plasma concentrations (average + SD) of enro- (A) and ciprofloxacin (B) 2, 4 and 100 hours after the first oral (PO) or intramuscular (IM) administration of 10 or 50 mg enrofloxacin/kg body weight to broiler chickens given during 5 consecutive days (n = 8). Values from the different treatment strategies with a different superscript within one time point, for the same compound ((A) or (B)), are statistically different at p < 0.05. The inserts show the chemical structure of enro- (A) and ciprofloxacin (B).
Mentions: The plasma concentrations of enro- and ciprofloxacin after oral or intramuscular administration are presented in Figure 1. Values present the mean (+ standard deviation, SD) of the 8 birds/group. Biotransformation of enro- to ciprofloxacin in broiler chickens is limited, as can be concluded from the concentration ranges measured for enrofloxacin: 1.66 to 14.04 μg/mL compared to ciprofloxacin: 0.08 to 0.65 μg/mL. The time of sampling, namely 2 or 4 h after first administration or 4 h after last administration (100 h), had a limited influence of the plasma levels of enro- and ciprofloxacin. However, dose escalation, from 10 mg/kg BW to 50 mg/kg BW, led to linearly increased plasma concentrations. At a dose of 10 mg/kg, the administration route (oral, PO, versus intramuscular, IM) altered the mean plasma concentrations only at 100 h (PO: 2.64 ± 0.42 μg/mL, IM: 1.66 ± 0.17 μg/mL) but not at 2 (PO: 3.02 ± 0.77 μg/mL, IM: 4.41 ± 1.26 μg/mL) and 4 h (PO: 2.69 ± 0.38 μg/mL, IM: 2.66 ± 0.31 μg/mL). In contrast, at the elevated dosage of 50 mg/kg, plasma levels at 2 (PO: 9.27 ± 1.15 μg/mL, IM: 14.04 ± 1.93 μg/mL) and 4 h (PO: 6.63 ± 1.12 μg/mL, IM: 12.66 ± 3.53 μg/mL) post administration were higher after parenteral administration, but not at 100 h (PO: 10.32 ± 1.62 μg/mL, IM: 8.54 ± 4.41 μg/mL).Figure 1

Bottom Line: 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.The 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium. mathias.devreese@ugent.be.

ABSTRACT

Background: The (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.

Results: The 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.

Conclusions: The 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.

Show MeSH
Related in: MedlinePlus