Pharmacokinetics, Residues And Bioavailabilities Of Norfloxacin In Carassius Auratus And Ctenopharyngodon Idellus L.

The present study investigated the pharmacokinetics, residues and bioavailabilities of norfloxacin (NFX) in Carassius auratus and Ctenopharyngodon idellus L. at different water temperature, administration routes and doses. The drug concentrations in serum, muscle, liver and kidney were determined by Re-high performance liquid chromatography (Re-HPLC). The research is the first one that ever has been done in China.Following a single-dosing intramuscular injection of 10 mg NFX/kg body weight in C. auratus at the water temperature (25.4±0.3)℃, the drug concentration in the serum amounted to the largest (6.6708±0.9242)μg/ml immediately at the first sampling point in 2 min, then declined. The results show that the serum concentration-time data were best described as a two-compartment open model with first order absorption, the half-life of distribution t_1/2α was (0.4231±0.0880)h, the half-life of elimination t_1/2β was (9.1613±3.6362)h.Following a single-dosing oral administration of 10 mg NFX/kg body weight in C. idellus at the water temperature (26±1)℃, the serum concentration-time data were best described as a two-compartment open model with first order absorption, the half-life of absorption t_1/2Ka was (0.1468±0.0046)h, the half-life of distribution t_1/2α was (0.5224±0.0812)h, the half-life of elimination t_1/2β was (82.8811±0.7391)h.Following a single-dosing intravenous injection of 10 mg NFX/kg weight in C. idellus at the water temperature (25.0±0.4)℃, the serum concentration-time data were best described as a three-compartment open model, the half-life of distribution in deep compartment t_1/2pi was (0.0252±0.0150)h, the half-life of distribution in shallow compartment t_1/2α was (0.7716±0.3687)h, the half-life of elimination t_1/2β was (151.42±21.093)h.Following a single-dosing oral administration of 10 mg NFX/kg weight in C. idellus at the water temperature (25.0±0.4)℃, the serum concentration-time data were best described as a two-compartment open model with first order absorption, the half-life of absorption t_1/2α Was (0.1157±0.0279)h, the half-life of distribution t_1/2α was (1.1299±0.3276)h, the half-life of elimination t_1/2β was (175.21±43.166)h.Following a single-dosing oral administration of 10 mg NFX/kg weight mixed feed in C. idellus at the water temperature (25.0±0.4)℃, the serum concentration-time data were best described as a two-compartment open model with first order absorption, the half-life of absorption t_1/2ka was (0.1949±0.0798)h, the half-life of distribution t_1/2α was (0.8836±0.1476)h, the half-life of elimination t_1/2β was (66.428±7.1048)h.In fact the drug concentration reached the peak concentration at the end of intravenous injection, the drug bioavailability could be considered as 100％. So the bioavailability of p.o. was 50.75％and the bioavailability of p.o. with feed was 33.74％by the contrast of i.v. in C. idellus.Two kinds of fish were treated with feed at the dosage of 10 mg/kg NFX per day for 5 days. No drugs were detected in muscle, serum and liver in C. auratus, the concentration in kidney is (0.0463±0.0134)μg/g and lower than 0.05μg/g on Day 8. As for C. idellus, no drugs were detected in muscle and the drug concentrations declined to (0.0287±0.0015)μg/ml, (0.0181±0.0042)μg/g and (0.0369±0.0037)μg/g in the serum, liver and kidney on Day 12 respectively, all below 0.05μg/ml orμg/g.Taking together, the following routes of administration could be sequenced in descending order according to their NFX absorption speeds: intravenous injection, intramuscular injection, oral administration, oral administration with feed. Following intravenous and intramuscular injection, the absorption of norfloxacin in aquatic animals was very rapid, and absorbed NFX was widely distributed with a rather high concentration in the tissues, and the elimination took time. So in cases of serious diseases in which fast pharmaceutical effect was required, the two routes would be preferred. In aquaculture practices, the most common routes are oral and oral administration with feed which boasted of fast absorption, wide distribution, long-time stay in the body and a concentration equal to the minimal inhibitory concentration for common bacteria.For the sake of consumers' wellbeing, we recommend the fish can be consumed only when no drug is detected in muscle and the drug concentrations are lower than 0.05μg/ml orμg/g in other tissues, the day we define as a withdrawal period. Therefore, we suggest a withdrawal period should last at least for 8 days in C. auratus at the water temperature (23±1)℃and 12 days in C. idellus at the water temperature (19±1)℃after they have been administered with feed at a dosage of 10mg/kg.