Pharmacodynamics(PD) And Pharmacokinetics/Pharmacodynamics (PK/PD) Model Of Enrofloxacin In Vitro Against Aeromonas Hydrophila

Aeromonas hydrophila(A.hydrophila) can cause people, livestock, poultry, aquatic animals suffering from bacterial diseases, A.hydrophila diseases breaks out in our country recently.But now it usually breaks out the bacterial diseases of creature in part of China,causing fish farming damage especially and public health problem. Enrofloxacin are broad spectrum antibacterial activity against gram-positive bacteria, negative bacteria and mycoplasma. From the nineties twentieth century enrofloxacin is extensive application in aquaculture,the drug resistance is also emerging. How to use existing antimicrobial drugs, to extend their useful life, to retard the emergence of drug resistance, to apply the new parameters to evaluate the new drug become studying hot spots.The thesis are to consist of minimal inhibitory concentration(MIC); minimal bactericidal concentration(MBC); the growth curve of A.hydrophila; the killing curve of A.hydrophila against encrofloxacin and post-antibiotic effect(PAE).The results showed that the MIC, MBC and MBC/MIC were 0.16μg/mL,0.32μg/mL and 2 respectively. A.hydrophila which cultured in fluid medium came into logarithmic growth phase after 2hours and lasted 10hours. The maximum drug action was reached after 4hours～8hours, it was concentration–dependent manner accroding to the results of killing curve.The PAE of 4MIC was longer than that of 8MIC, but no remarkable difference was discovered between them(P>0.05). Enrofloxacin had the most effective inhibition on A.hydrophila at pH7～8. The action of enrofloxacin was influenced mostly by divalent cation such as the Mg2+ and the action decreased as the concentration dropped. Bateria counting showed the blood serum could degrade the drug action and no significant effect on enrofloxacin activity. Enrofloxacin had the most effective inhibition on A.hydrophila at 30 to 40℃temperature.By in vitro PK/PD model, PK/PD parameter of A.hydrophila against enrofloxacin was studied. In the invitro model with elimination half-life of 100h, A.hydrophila was inhibited for 6h by 2MIC enrofloxacin and was continuously inhibited in the entire experiment period of 24h by 4MIC, 8MIC and 16MIC enrofloxacin. In the invitro model with elimination half-life of 168h, the inhibitation effect of 2MIC enrofloxacin on A.hydrophila lasted for 6h and the bacteria regrew after that. 4MIC, 8MIC and 16MIC enrofloxacin showed continously inhabitative action on A.hydrophila amount of of enrofloxacin in 1h. The A.hydrophila decreased 0.31±0.01, 1.60±0.01, 0.70±0.08, 0.90±0.10lg(CFU/mL), when it exposed to 2MIC,4MIC,8MIC and 16MIC in the invitro model with elimination half-life of 100h. The A.hydrophila decreased 0.33±0.02, 1.60±0.04,0.75±0.08, 0.93±0.15l g(CFU/mL),when it exposed to 2MIC,4MIC,8MIC and 16MIC in the invitro model with elimination half-life of 168h. The concentration-time data was analyzed by the software of 3P97,it show that R2 is exceed 0.95 and the concentration of enrofloxacin is 0.35±0.04μg/mL, 0.66±0.01μg/mL,1.50±0.16μg/mL and 2.82±0.07μg/mL in beginning of the PK/PD model. The t1/2β, V, CL are 103.94±6.2631h,1.0±0.0171L/kg and 0.0095±0.0215 L·(kg·h) respectively, and it is 170.11±5.3009h;0.92±0.0993L/kg;0.0055±0.0014 L·(kg·h) respectively.It is concluded that continous inhabitation of A.hydrophila by enrofloxacin could be achieved at the condition of AUC0→24/MIC≥75.24±13.24, Cmax/MIC>4.10±0.12.