Study On The PK-PD Modeling Of Florfenicol Against Streptococcus Agalactiae

To combine the pharmacokinetics of florfenicol after intramuscular(i.m.), oral and intraperitoneal administration with the in vitro and ex vivo activities of florfenicol against a pathogenic strain of Streptococcus agalactiae in plasma of tilapia. So, the ex vivo PK-PD model of florfenicol against Streptococcus agalactiae were established. It was suggestted that the models be used to provide a rational basis for designing dosage regimen.1. The determination of in vitro sensibility of florfenicolAntimicrobial susceptibility testing of Streptococcus agalactiae using broth dilution method. The MIC(Minimal Inhibitory Concentration) and MBC(Minimal Bactericidal Concentration) for Streptococcus agalactiae were 2μg/m L and 4 μg/m L,respectively. The ratio of MBC/MIC was 2.2. The Establishment of the analysis methods of florfenicolA HPLC methord was developed for the determination of florfenicol in tilapia plasma. Florfenicol in the samples was extracted by the ethyl acetate. Mobile phase consisted of acetonitrile and water. The levels of absolute recoveries of florfenicol were more than 90 %. The lower limit of quantification of florfenicol in the body fluids was 0.01 μg/m L. The results indicated that the detection method of florfenicol was rapid, simple and sensitive, which could satisfy the following study.3. Study on the ex vivo pk-pd modeling of florfenicol against Streptococcus agalactiae in tilapia plasma.The concentrations of florfenicol in plasma was analysised by HPLC and the concentration-time data were analyzed by the Win Nolin software.The main PK parameters were described as follows: Tmax were 4 h、1 h、0.5 h, respectively; T1/2λz were 10.45 h、13.13 h、15.37 h, respectively; AUC were 91.06 μg·h/m L、61.96 μg·h/m L、114.50 μg·h/m L, respectively; Vd were 2.48 L/kg、4.59 L/kg、2.90 L/kg, respectively; CL were 0.16 L/h·kg、0.24 L/h·kg、1.31 L/h·kg, respectively; MRT were 16.70 h、12.74 h、20.68 h, respectively;The MIC and MBC of florfenicol against the Streptococcus agalactiae in tilapia plasma were 4 μg/m L and 8 μg/m L, respectively, both were 2 times higher than those in MH broth. The in vivo pk parameters combining with the in vitro MIC and MBC to provide the various PK-PD indices(AUC/MIC). The ex vivo growth inhibition data after intraperitoneal administrations was fitted to the inhibitory effect sigmoid Emax model, the values of AUC24h/MIC required to produce bacteriostasis(E=0) was 25.08 h, bactericidal activity(E=1,2) was 33.45 h、56.10 h, separately, the calculated corresponding dosages of florfenicol were 6.57、8.76、14.70 mg/kg b.w..