Abstract
The pharmacokinetics and tissue distribution of enrofloxacin were determined in Yellow River carp (Cyprinus carpio haematopterus) reared at 20°C after single oral administration of enrofloxacin at 10 mg·kg−1 body weight (BW). Plasma, bile, and different tissue samples, including liver, kidney, gill, gut, and skin-muscle, were collected at predetermined times points. An HPLC method was developed to simultaneously determine the concentrations of enrofloxacin and its metabolite, ciprofloxacin. However, ciprofloxacin was only detectable in some liver samples with trace levels. Then the average enrofloxacin concentrations vs. time data were subjected to a non-compartmental analysis using WinNonLin 5.2 software. Multiple peaking profiles were observed in all enrofloxacin concentration-time curves. The peak concentration (Cmax) values were observed as 0.79, 1.01, 2.09, 2.85, 4.34, 10.78, and 13.07 μg·ml−1 (or g−1) in plasma, skin-muscle, gill, kidney, liver, bile, and gut, respectively, and the corresponding time to reach peak concentration (Tmax) was 8, 8, 1, 8, 1, 72, and 4 h, respectively. The values of elimination half-life (T1/2λZ) of enrofloxacin in different tissues was in the following order: gill (291.13 h) > liver (222.29 h) > kidney (157.22 h) > plasma (129.44 h) > gut (91.47 h) > skin-muscle (87.77 h) > bile (86.22 h). The present results showed that enrofloxacin had a wide distribution in different tissues, however slow absorption and elimination in Yellow River carp. Additionally, enrofloxacin exhibited large distribution in bile, indicating that bile excretion might be the primary elimination route of enrofloxacin in Yellow River carp. A withdrawal period was calculated as 379.2 °C-day for single oral dosing of enrofloxacin at 10 mg/kg BW. Based on the calculated PK/PD indices of AUC/MIC or Cmax/MIC, the current enrofloxacin dosing regimen might have a positive therapeutic effect on the infection of Flavobacterium columnare, Aeromonas sobria, or Aeromonas hydrophila. However, the depletion study following multiple oral doses should be carried out in Yellow River carp reared at lower temperatures, and the withdrawal period should also be further calculated.
Highlights
Common carp (Cyprinus carpio), with the characteristics of strong adaptability, excellent reproductive ability, and rich nutritional value, has been reared in Asia for more than 2 000 years [1]
The results showed that all interand intra-day coefficients of variation were below 4.78% for enrofloxacin and below 5.79% for ciprofloxacin
While the AUC ratio between ciprofloxacin and enrofloxacin was high up to 20, 51.5, and 55% in donkeys [35], pigs [36], and sheep [37], respectively. These results indicated that the extent of demethylation of enrofloxacin to ciprofloxacin was low in many fish species compared with homoiothermic species
Summary
Common carp (Cyprinus carpio), with the characteristics of strong adaptability, excellent reproductive ability, and rich nutritional value, has been reared in Asia for more than 2 000 years [1]. With the development of freshwater aquaculture, Yellow River carp have been cultivated artificially in a wide temperature range of 5–28◦C, and it has stronger disease resistance and more delicious meat [3]. Lepidorthosis is a common disease in the Yellow River carp, which has caused substantial economic, and its pathogenic bacteria included Aeromonas hydrophila and Aeromonas sobria [5]. Columnaris disease is another common disease in the Yellow River carp caused by Flavobacterium columnare [6]. To reduce these losses, treatment with effective antibacterial agents is necessary
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