| The article reported pharmacodynamics of orbifloxacin which often be used specially for animals,established orbifloxacin reversed phase high-performance liquid chromatography in plasma and tissues as well as extraction method in tissues. Pharmacokinetics and residual of orbifloxacin in crucian tissues were also studied. The results as follows:1.For the first time,the paper reported the antibiosis of Orbifloxacin on pathogenic bacteria in vitro.Paper disk method and tube dilution method have been used to research the effect of antibiosis in vitro and MIC of Orbifloxacin on pathogenic bacteria(E.Coli, Aeromonas hydrophila,Klebsiella oxytoca,Myxococcus piscicola,P.Fluorescens, Staphylococci) of aquatic,Orbifloxacin is a kind of medicine which is used specially for animals.The results showed that these aquatic pathogenic bacteria were midrange sensitive and hyper sensitive to Orbifloxacin,the bacteria of hyper sensitive include Klebsiella oxytoca and Staphylococci,other bacteria belong to midrange sensitive. Orbifloxacin has fairly strong bacteriostatic action to Klebsiella oxytoca and Myxococcus piscicola,the lowest MIC below 0.125μg/ml.MIC was 0.5μg/ml for Aeromonas hydrophila and P.Fluorescens,MIC of Staphylococci and E.Coli was respectively 0.125μg/ml and 4μg/ml.2.For the first time,orbifloxacin reversed phase high-performance liquid chromatography was established.According to the absorption light spectrum,chemical constitution,dissolubility and other peculiarity of orbifloxacin and referring reversed phase high-performance liquid chromatography detection condition for other FQNS,bolting the composition and percentage of mobile phase,wavelength,flow rate,PH and column temperature etc.Chromatography separation was achieved on a shim-pak.ODS-C18(4μm, 4.6×150mm) column using 0.02%trifluoroacetic acid and acetonitrile(V/V,75: 25),to add to sodium heptanesulfonate 0.5g/L as the mobile phase.PH=2.5 use phosphoric acid accommodation.The UV detection wavelength was set at 279 nm,a flow rate of 0.8 ml/min with a column temperature at 30℃.Retention time were 10 minutes,the lowest detectable limit was 0.01μg/ml.3.For the first time,orbifloxacin extraction method in tissues was established.Regard recovery rate as reference index,after repeatedly comparing pure solvent, acid and base extraction for orbifloxacin in tissues,decided to adopting pure solvent extraction so as to obtain high recovery rate and foreign matter was completely separated.Means:Tissue was extracted by acetonitrile 6ml at first,collected to centrifuge tube and,centrifuged five minutes(4000r/min) after oscillation, supernatant was degreased by N-hexane 6ml;that was derived aqueous phase by separating after oscillation and standing.Aqueous phase was blown dry through Nitrogen gas at 60℃water temperature before it was dissolved.The tissue recovery rate ranged from 83.7%to 99.12%.4.For the first time,pharmacokinetics of orbifloxacin in crucian was determined.The plasma concentration-time curve of orbifloxacin fitted to a two-compartment open model with absorption:C=6.0930.773t+3.7630.028t-9.856-1.286t.the character of pharmacokinetics:Orbifloxacin was rapidly absorbed in plasma of crucian,short peak time(Tmax 1.773h),high peak plasma concentration(Cmax 4.115μg/ml),fast distribution(T1/2αwas 0.896),slow elimination(T1/2βwas 24.045h),large area under the plasma concentration time curve(approximately 130.753mg·h/L).5.The elimination regularity of orbifloxacin was analyzed in crucian,and formulated withdrawal time.Orbifloxacin has a strong penetration in tissues and distribute generally.The elimination half-time of liver,kidney,muscle and skin was 12.158,18.382,10.374 and 11.493 h respectively calculated by formula WDT.Orbifloxacin has the highest concentration in kidney and liver,which explained that orbifloxacin was absorpted quickly by kidney and liver,they are chief organs conceming drug metabolism.We suggest that withdrawal time should be 8d at least after single i.m.(10mg/kg) of orbifloxacin in crucian calculated by software WT1.4,according to the maximum residues limit(MRL ) of 10gg/kg in kidney.The results of studies showed that orbifloxacin had a strong bacteriostasis to these aquatic pathogenic bacteria in vitro,besides it had a feature that quick absorption extensive distribution,slow elimination,long-maintained valid drug concentration,short withdrawal time,low residual after in crucian.So with the hope that orbifloxacin would be use as a new drug for fish diseases prevention after further experiment.
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