Abstract:
The pharmacokinetics of danofloxacin in healthy and Aeromonas hydrophila infected Acipenser schrenckii were investigated, so as to provide scientific basis for the application of danofloxacin in aquaculture. About 106 CFU per mL was inoculated to Amur sturgeon to induce the disease model. The 150 healthy fish and over 200 infected fish randomly divided into two groups according to different routes of administration. TheAmur sturgeon are divided into 4 groups for the experiment, the healthy group for intravenous, the healthy group for oral administration, the diseased group for intravenous and the diseased group for oral administration.The dose for intravenous and oral administrat ion were all 10mg/ kg. At different times after administration the blood were collected. High-performance liquid Chromatography(HPLC) was used to determine the concentration of danofloxacin in plasma of Amur Strugeon and the MCPKP pharmacokinetic software was used to analyze themedicinal concentration-time courses. Using a C18 colume, the mobile phase consisted of Acetonitrile/ tridistilled water(15:85). The fluorescence acceleration and emission wavelenght were 280 nm and 450 nm. The protein of samples were deprived with methyl alcohol. The precipitated mixture was shaken and then centrifuged, the filtrate was evaporated to dryness with Nitrogen fumes. Within the range of 0.005-1.0Lg/mL, danofloxacin had a good linearity. The lowest detectability was 0.005Lg#mL-1 and the average recovery of danofloxacin was above 84%. The within day and day- to- day precision expressed by RSD was less than 10% at three drug levels (0.005、0.1 and 1Lg/mL). The pharmacokinetics and bioavailability of danofloxacin in healthy and diseased Amur sturgeon infected with Aeromonas hydrophila were studied. The pharmacokinetic characterist ics of danofloxacin in healthy group is described by the three compartment open model by intravenous. The data is C=5.830- 5.582t+ 4.162- 1.157t+ 0.852- 0.029t, themain pharmacokinetic parameters of danofloxin; distrbution half time(t1/ 2A) 0.55 h; elimination half time(t1/ 2B) 22.19 h; area under the plasma drug concentration- time curve(AUC) 34.23 mg/(L#h), apparent volume of the central compartment(Vl) 0.92L/ kg,apparent volume of a drug distribution in body(Vb) is 10.14L/ kg, kel is 0.32/ h. The Vl of diseased sturgeon by single intravenous danofloxacin decreased to 0.29L/ kg. The elimination of danofloxacin between healthy and diseased sturgeon by intravenous is same. The pharmacokinetic characteristics of danofloxacin by oral administration in healthy sturgenon is described by the two compartment open moldel with first order absorb, the data is described with C=1.278e- 0.073t + 0.177e- 01089t -1.455e- 01329t, the main pharmacokinetic parameters of danofloxin t1/ 2ka9.49h, t1/ 2B 78.27h, time of reaching maximum drug concentration after a single i. m. injection of a drug(Tmaxmax) 0.79mg/ mL,slopes of distribution phrase(A) 0.07/ h, The result showed that the absorption distribution and elimination of danofloxacin changed markedly. The Adecreased to 0.05/ h. Meanwhile the rate of elimination slowed, t1/ 2B increased to 93.99h, tmax prolonged to 9.06h, the Cmax decreased to 0.59mg/mL. the bioavailability of danofloxacin in healthy and diseased sturgeon is 96.50% and 94.44% by oral administration. The high bioavailability in healthy and diseased group showed that danofloxacin is suitable to cure the bacterial infection Amur sturgeon. Danofloxacin can be given by oral administrat ion at dose of 10mg/ kg interval 2 days to prevent infected Ah Amur sturgeon.