| The crucian carp, as one of important food fish in our country, were widely distributed in china, except in the western plateau region. The carps’ ability to adapt is very strong which can all survive whether in deep or shallow water, in running or still water, whether in high (32 0C) or low (0℃) temperature, in strong alkali (pH=9) or salt(4.5%). The use of antibacterial drug could prevent from and treat for some explosive bacterial disease, which result from the increasing breeding density with the intensive aquaculture. Enrofloxacin belongs to the chemical synthesis antibacterial drugs of fluoroquinolones, and widely used for prevention from aquatic animal diseases especially bacterial disease. But the lack of normative breeding or interest-driven made the drug abuse and unreasonable use becomes more and more serious, that lead to the generation of drug-resistant bacteria. Aeromonas hydrophila belongs to vibrionaceae aeromonas as a mesophilic typical bacteria that could cause masse mortality of crucian carps. In this study, the pharmacokinetics and post-antibio tic effect of enrofloxacin were investigated in the crucian carpst from sanshui company of foshan city, Guangdong province, and more details is as follows:1. It was aimed at comparing the post-antibiotic effect (PAE) of enrofloxacin and other conmmon antibiotics in aquaculture on Aeromonas hydrophila (A. hydrophila).The minimal inhibitory concentration (MIC) and minimal bactericidal concentration(MBC) of the drugs were 0.016 and 0.023 μg/mL (enrofloxcin)、0.250 and 0.500 μg/mL(doxycycline)、0.250 and 0.500 μg/mL (norfloxacin), 1 and 4 μg/mL (florfenicol), 2 and 4 μg/mL (thiamphenicol) respectively; there were a certain post-antibiotic effect(PAE) at different levels of drug concentration, among them, the PAE of doxycycline was up to 2.84 h. It was described that the PAE of 5 kind of antibiotics on A. hydrophila existed, and were in a concentration-dependent manner at 0MIC, 1/2MIC, 1MIC, 2MIC and 4MIC.2. The comparative pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin was studied after oral (PO) , intramuscular (IM) and bath administration at a dose of 10 mg/kg.The pharmacokinetics of plasma concentration of enrofloxacin after PO and IM administration conformed to a 2-compartment open model by compartmental modeling,while the absorption half-lif (T1/2ka) , the distribution half-life (T1/2a), the elimination half-life (T1/2λz),time to peak (Tmax),area under the concentration-time curve (AUC)values, and total body clearance (CL/F) were 0.13 and 0.65 h, 2.22 and 24.07 h, 62.17 and 80.95 h, 0.68 and 4.08 h, 162.72 and 223.46 μg h/mL, 0.06 and 0.04 L/h/kg,respectively. And the result after bath was calculated by uncompartmental modeling,while the elimination half-life (T1/2λz),maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) were 61.15 h, 0.36 μg/mL and 14.91 μg h/mL. So, enrofloxacin was absorbed and distributed faster after PO administration than IM, except for the same broad distribution, eliminated faster than bath administration ,but at similar rate with IM.The pharmacokinetics of ciprofloxacin after PO and IM administration were calculated by uncompartmental modeling, and the elimination half-life(T1/2λz), time to peak (Tmax) and area under the concentration-time curve (AUC) were 129.99 and 137.71 h, 2.00 and 48.00 h, 3.30 and 4.85 μg h/mL, respectively; the ratio of AUC between ciprofloxacin and enrofloxacin were 2.17 and 2.03 %. After bath administration,enrofloxacin was not detected in plasma. Above all, the concentration of ciprofloxacin metabolic transformed from enrofloxacin was very low, so it was suggested that enrofloxacin should be focused for its bateriostatic action in aquatic livestock.3. The comparative pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin was studied in healthy and infected crucian carps at a dose of 10 mg/kg.After disease modeling for A. hydrophila was built by selecting the best strain to infect and the best inoculum size using single facter experiment, we studied at the effect of A.hydrophila on the pharmacokinetics of drugs in crucian carp. The pharmacokinetics of drugs were calculated by uncompartmental modelling, and the elimination half-life(T1/2λz), time to peak (Tmax), maximum plasma concentration (Cmax), area under the concentration-time curve (AUC), volume of distribution at steady-state (Vd) and total body clearance (CL/F) were 64.66 and 73.70 h, 0.5 and 0.75 h, 3.55 and 2.66 μg/mL,163.04 and 137.43 μg h/mL, 5.72 and 7.74 L/kg, 0.06 and 0.07 L/h/kg, respectively. The concentration of enrofloxacin in infected animals was at a slighter lower on the whole than the healthy; under the condition of infection, maximum plasma concentration was lengthened as much as 50%, drug’s total absorption decreased and elimination was slower, but there was no change at distribution.Ciprofloxacin, the main metabolite of enrofloxacin was also calculated by uncompartmental modelling. The elimination half-life(T1/2λz), time to peak (Tmax),maximum plasma concentration (Cmax), area under the concentration-time curve (AUC)were 90.01 and 75.57 h, 36 and 48 h, 0.031 and 0.046 μg/mL, 4.79 and 6.47 μg h/mL,respectively; the ratio of AUC between ciprofloxacin and enrofloxacin were 2.94 and 4.71 %. Above all, the concentration of ciprofloxacin metabolic transformed from enrofloxacin was very low in aquatic livestock. |
