Study On Effect Of Platycodin On Pharmacokinetics Of Difloxacin And Distribution In Lung In Chickens After Oral Administration

Objective: To study the effect of platycodin on pharmacokinetics of difloxacin in chickens and distribution in lung after oral administration. Methods: 195 healthy chickens were allocated into five groups of 39 chickens each at random. The chickens in groupâ… were orally given with single dose of Difloxacin at 10mg/kg·b·w ,The chickens in groupâ…¡were orally given with single dose of Difloxaein at 10mg/kg·b·w and platycodin at 20mg/kg·b·w simultaneously. The chickens in groupâ…¢were orally given with single dose of Difloxacin at 10mg/kg·b·w and platycodin at 40mg/kg·b·w simultaneously. The chickens in groupâ…£were orally given with single dose of Difloxacin at 10mg/kg·b·w and platycodin at 60mg/kg·b·w simultaneously. The chickens in groupâ…¤were intravenously injected with single dose of Difloxacin at 10mg/kg·b·w. The concentrations of Difloxacin in plasma and lung were determined by reverse phase high performance liquid chromatography with a limit of detection of 0.01 mg/L in plasma and 0.05μg/g in tissues, respectively. The pharmacokinetic variables were calculated by 3P97 PK program and SPSS(11.0) program. Results: The Model were fitted a two-compartment Model with 1st Order Absorption(weight=1).The main pharrnacokinetics parameters and calculated-equations in chickens were as follows, respectively: Groupâ… : T_1/2Ka= (0.037±0.002) h,T_1/2α=(0.499±0.051) h, T_1/β=(14.429±2.306) h, T_peak=(0.500±0.278) h, C_max=(1.834±0.077) mg/L, AUC=(16.294±1.662) (mg/L·h), Ka=(18.506±0.494) (1/h), MRT_{0→36(h)}= (14.228±2.187) h, C=2.256e^-1.389t+0.737e^-0.048t -2.993e^-18.506t。Groupâ…¡: T_1/2Ka=(0.170±0.034) h,T₍1/2α=(2.188±0.929) h, T_1/2β=(38.160±3.232) h, T peak=(0.750±0.149) h, C_max=(0.828±0.040) mg/L, AUC=(19.633±1.512) (mg/L·h), Ka=(4.089±1.226) (1/h), MRT_{0→36(h)}= (17.665±2.079) h, C=0.729e^-0.317t+0.321e^-0.018t -1.050e^-4.089t。Groupâ…¢: T_1/2Ka=(0.552±0.065) h,T_1/2α=(1.389±0.627) h, T_1/2β=(36.338±4.895) h, T_peak=(1.000±0.125) h, C max=(1.010±0.014) mg/L, AUC=(22.874±0.315) (mg/L·h), Ka=(1.256±0.150) (1/h), MRT_{0→36(h)}=(17.314±2.768 )h, C =2.282·e^0.499t+0.396·e^-0.019t -2.678e^-1.25t。Groupâ…£: T_1/2Ka=(0.430±0.074) h,T_{1/2α=(1.646±0.226) h, T1/2β=(71.680±4.214) h, T peak=(1.000±0.041) h, C9max}=(1.439±0.016) mg/L, AUC=(32.372±1.579) (mg/L·h), Ka=(1.256±0.205) (1/h) , MRT_{0→36(h)}= (16.2904±2.276) h,C =2.694e^-0.421t +0.279e^-0.001t -2.973e^-1.611t。Groupâ…¤: T_1/2α=(0.852±0.329) h, T_1/21β=(26.367±3.142) h, AUC=(24.704±1.202) (mg/L·h), MRT_{0→36(h)}=(14.435±2.295) h, C =5.124e^-Ï€t+2.824e^-0.814t+0.533e^-0.026t。Conclusions:â‘ Difloxacin in healthy chickens was quickly absorbed with high concentration in plasma, distributed widespread, and eliminated slowly.â‘¡Platycodin could influence the pharmacokinetic variables of Difloxacin in healthy chickens significantly: decreased the speed of absorption, but enhanced the degree of absorption; accelerated the distribution from blood to tissues ; retarded the speed of elimination, increased the time of drug action; increased the bioavailability of Difloxacin; Platycodin increased the distribution volume of Difloxacin, manifest that Platycodin make Difloxacin distributed more widespread, furthermore, profit to cure infection of the deep part tissue.â‘¢When Platycodin and Difloxacin were orally administered together, the Difloxacin concentration of lung tissue in healthy chickens was increased notably. It was showed that Platycodin is the hylic foundation of the Leading action of platycodon root.