Pharmacokinetics Of Two Quinolones In Crucian Carp At Three Water Temperature

In this thesis, enrofloxacin and norfloxacin pharmacokinetics was studied in crucian carp at different temperatures. Drugs were organized to crucian carps 5 mg/kg body weight at temperatures of 15℃, 20℃and 25℃, respectively. After administration plasma kidney and liver samples were collected. The drug concentration of samples was determined with high performance liquid chromatography (HPLC) method. The concentration-time data were treated and with practical pharmacokinetics program (3P97).Enrofloxacin concentration-time data were all conformed to two-compartment model with first order absorption at three water temperatures, in plasma, kidney and liver. At temperatures of 15℃, 20℃and 25℃, in plasma, the time-point of maximal concentration (Tpeak) was 0.504 h, 0.228 h and 0.183 h; the absorption half life (T1/2α) was 0.925 h,0.804 h and 0.696 h; the elimination half-life (T1/2β) was 235.1 h, 188.4 h and 132.9 h; the clearance rate (CLC) was 0.035 L/kg/h, 0.062 L/kg/h and 0.085 L/kg/h; maximal concentration (Cmax) was 0.515μg/mL, 0.462μg/mL and 0.318μg/mL; area under the concentration-time curve (AUC) was 144.1μg/mL·h, 81.12μg/mL·h and 31.61μg/mL·h, respectively. In kidney and liver, metabolism of drugs was similar to in plasma. Metabolism of enrofloxacin in crucian carp showed: in a certain temperature range, the rate of drug absorption and distribution at higher temperature is larger than this at lower temperature; the rate of elimination was lager at higher temperature; but the amount of drug absorption was lower at higher temperature.Norfloxacin experimental data showed that all drug concentration-time data of three tissues conformed to two-compartment model with first order absorption at three water temperatures.At three water temperatures (15℃, 20℃and 25℃), the norfloxacin in carp plasma, the time-point of maximal concentration (Tpeak) was 1.688 h, 1.593 h and 1.128 h; the absorption half life (T1/2α) was 1.868 h, 1.662 h and 1.606 h; the elimination half-life (T1/2β) was 309.6 h, 227.7 h and 177.4 h; the clearance rate (CLC) was 0.608 L/kg/h, 0.632 L/kg/h and 0.688 L/kg/h; maximal concentration (Cmax) was 0.029μg/mL, 0.039μg/mL and 0.044μg/mL; area under the concentration-time curve (AUC) was 8.213μg/mL·h, 7.808μg/mL·h and 7.067μg/mL·h, respectively. Metabolism of the drug in the kidney and liver showed similar to that in plasma. Metabolism of norfloxacin in crucian carp showed: in a certain temperature range, the distribution and absorption rate of norfloxacin increased with temperature; the elimination rate also become larger while temperature increased; while temperature increased the amount of drug absorption become lower; maximal concentration become lager while temperature increased. Under the same experimental conditions, enrofloxacin and norfloxacin experiment were carried out, at 20℃in carp plasma, t1/2αwere 0.804 h and 1.662 h, t1/2βwere 188.4 h and 227.7 h, AUC were to 81.12μg/mL·h and 7.808μg/mL·h, respectively. Pharmacokinetics of enrofloxacin and norfloxacin was obviously different in crucian carp. the absorption rate and elimination rate of enrofloxacin were higher than those of norfloxacin. The amount of drug absorption of enrofloxacin was higher than that of norfloxacin. Different drugs has different metabolism.