| Danofloxacin is a kind of fluoroquinolones exclusive used in veterinary medicine, and it has better water-solubility and can be administered by many pathway, it has wide antibacterial spectrum, and its antimicrobial activity is powerful, it also has good pharmacokinetics character Meanwhile its adverse effect is less, its cross tolerance with other antibacterials is less. Danofloxacin has been used in veterinary surgeon to treat bacterial infection of some animals. Amur sturgeon has thick muscle and soft bone, it is delicious, it has high economic value.Amur sturgeon has been artificial breeding for many years in China. With the development of the cultivation of Amur sturgeon, it often has been infected by Ah, this is a restrict factor for sustainable development, so some medicine must be investigated for Amur sturgeon. Some quinolones have already been used to treat diseased fishes, but we have not found any reports about the danfloxacin used in aquiculture. In this study, the activites in vitro and influence of 4 factors of danofloxacin against Ah, efficacy for Amur sturgeon infected by Ah, the pharmacokinetics of danofloxacin in vivo in healthy and Ah infected Amur sturgeon, detection for residual of danfloxacin in Amur sturgeon and safety evaluation of danofloxacin in Amur sturgeon were investigated firstly. So as to appraise its feasibility and security, to provide the scientific basis for the application of danofloxacin in aquculture. The result is: 1 Minimal inhibitory concentration (MIC) of danofloxacin and influences of pH, various concentration of Mg2+,inoculum size of bacteria,calf blood serum on the vitro activity against Ah wre determined by two-fold dilution. MIC and MBC is 0.05mg·L-1 and 0.1 mg·L-1 separately. Bacteriostasis activity is the most powerful when pH is 8; over 50% of calf blood serum in nutrient medium MBC is affected obviously, while inoculum size of bacteria is 107 bacteriostasis activity is depressed, Mg2+ can influence the MIC and MBC evidently. 2 The result of efficacy of danofloxacin against experimentally infected by Ah of Amur sturgeon shows that the death rate of is 15,0,0% of given respectively danofloxacin at 2.5,10,20 mg·kg-1, and once every day for four days. The results showed that the efficacy of danofloxacin(10,20 mg·kg-1) is as same as enrofloxacin(10 mg·kg-1), and is better than florfenicol(50 mg·kg-1) and gantanol(100 mg·kg-1). 3 The pharmacokinetics of danofloxacin in healthy and Aeromonas hydrophila infected Amur sturgeon were investigated by high performance liquid chromatography(HPLC). The Amur sturgeon is 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 administration were all 10mg·kg-1.MCPKP pharmacokinetic software was used to analyze the medicinal concentration-time courses. The pharmacokinetics and bioavailability of danofloxacin in healthy and diseased Amur sturgeon infected with Aeromonas hydrophila were studied. The pharmacokinetic characteristics 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,the main pharmacokinetic parameters of danofloxin: distributionhalf-time (t1/2α) 0.552h; elimination half-time (t1/2β) 22.186h;area under the plasma drug concentration-time curve (AUC) 34.226 mg·(L·h)-1,apparent volume of the central compartment (Vl) 0.922 L·kg-1, VB is 10.144 L·kg-1,kel is 0.317 h-1 .The Vl of diseased sturgeon by single intravenous danofloxacin decreased to 0.290 L·kg-1. The pharmacokinetic characteristics of danofloxacin by oral administration in healthy sturgeon is described by the two compartment open model with first order absorb, the data is described with C=1.278e-0.073t+0.177e-0.089t-1.455e-0.329t, the main pharmacokinetic parameters of danofloxin t1/2ka 9.491h, t1/2β78.267 h,time of reaching maximum drug concentration after a single injection of a drug (Tmax)6.284 h,maximum drug concentration (Cmax)0.791 mg·ml-1, slopes of distribution phrase(α)0.073 h-1, The result showed that the absorption distribution and elimination of danofloxacin changed markedly. The αdecreased to 0.050 h-1. Meanwhile the rate of elimination slowed, t1/2βincreased to 93.987h, Tmax prolonged to 9.060 h, the Cmax decreased to 0.585 mg·ml-1. The bioavailability of danofloxacin in healthy and diseased sturgeon is 96.503%和94.435% by oral administration. The high bioavailability in healthy and diseased group showed that danofloxacin is suitable to cure the bacterial infection .Danofloxacin can be given to Amur sturgeon by oral administration at dose of 10 mg·kg-1 interval 2 days. 4 Using HPLC, detected the danofloxacin concentration in serum, liver, kidney, muscle and gill by oral administration at dose 10 mg·kg-1 for four times .The result showed that: danofloxacin distributed to serum, liver, kidney, gill and muscle.The concentration of danofloxacin can not be detected after oral administration for 9 days, and the concentration of danofloxacin in liver and kidney were higher than in serum, gill and muscle. According the result we think the withdrawal time is 9 days. 5 The acute toxicity test of danofloxacin in Amur sturgeon was studied. The dose of danofloxacin by oral administration or abdominal cavity injection .The LD50 (mediallethaldose) and 95% confidence of LD50 of danofloxacin in sturgeon by abdominal cavity injection were 429.47mg·kg-1 and 425.22433.66 mg.kg-1 respectively, and were 1502.1040 mg·kg-1 and 1307.88631738.6013 mg·kg-1 respectively by oral administration. The tissue section showed that the hepatic cell cord dissolved, the hepatic cell cellularswelling and deformation. The cell nucleus liquid chromatography (nucleus of hepatic cell karyolysised).The sinusoid narrowed, the erythrocyte in them changed the form. The ultrastructure of liver cell showed that the cells were filled with more lipid droplet, the mitochondrion break, rough endoplasmic reticulum occur rarefaction and fragmentation and Lysosome disrupted. 6 The effects of danofloxacin by oral administration for 20 days at dosage of 20,50 and 100 mg·kg-1 on the toxicity of Amur sturgeon wre studied. The result showed that at 5th day, the SOD activity of 100 mg·kg-1 group is higher than the control group significantly , and at 10th and 15th day the activity in these three test group all remain higher value than control group. The activity of SOD in plasma remained lower level by oral danofloxacin of dosage at 20 ,50 and 100 mg·kg-1. The SOD activity in erythrocyte remain high level than control group. The activity of CAT in liver is higher evidently than the control group , but at 20th day only the CAT activity of 100 mg·kg-1 group is lower than the control group obviously . CAT activity in erythrocyte is higher than control group obviously. The activity of Na+,K+-ATP in liver and erythrocyte is not significant compared with control group(P>0.05). but danofloxacin decreased its activity in gill. The GSH-px activity in erythrocyte of 100 mg·kg-1 is higher than other test group(P<0.05). The NO concentration in liver plasma is stable compared with control group. The MDA concentration in liver and erythrocyte remain unchanged, but can raise up in plasma(P>0.05). The activity of GST in erythrocyte is not be affected by dnaofloxacin. 7 At 15th day ,GOT activity in liver of 100 mg·kg-1 is lower than control and other test group obviously. GPT activrity in liver almost remain unchanged. The activity of GOT and GPT in plasma all induced by danofloxacin. The BUN and Cr concentration in plasma of test group is higher than control group. The concentration of K+ in plasma of 50 and 100 mg·kg-1 is lower than control group(P<0.05)at 20th day, but Na+ only in 100mg·kg-1 is ohigher than control(P<0.01).The concentration of Cl-1 of 100 mg·kg-1 is higher markly than control group(P<0.01) only at 15th and 20th day , Ca2+ is lower than control group, but not obviously(P>0.05). The number of erythrocyte in test group all increased to contrast control group, but the leukocyte number remain unchanged. The result showed that the effect of danofloxacin against serum and liver protein content is not remarkable, haematoglobin(Hb) content is lower than control group only at 20th day. 8 Danofloxacin can decrease the content of lysozyme in liver and plasma, and 100 mg·kg-1 dosage is markly. The idellus liver and spleen is not changed in all test group compared with control group. The phagocytic activity of leucocyte changed by danofloxacin administration. 9 The erythrocyte micronucleus remained stable, but nuclear anomalies in test group raised markly comparition control group. The result showed that the nuclear anomalies is the highestat 10th day, then began decreased but still is higher obviously than control group.
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