Research On Biopharmaceutic Classification And Pharmacokinetic Characteristics Of Thiamphenicol And Florfenicol In Ducks

Thiamphenicol（TAP）and fluphenicol（FFC）belong to phenicols antibiotic,and they have been used in veterinary clinic because of the wide antimicrobial spectrum,effective antibacterial action and low side effect.TAP and FFC are mainly be used to prevent and cure bacterial disease of chicken,pig,fish and so on,but there are few reports on duck.At present,there are some pharmacokinetics studies about TAP and FFC in chicken,pig,fish and other animals at home and abroad.However,there is no report about the pharmacokinetics study of TAP in duck,and there are pharmacokinetics study about FFC only at oral and intravenous administration.Biopharmaceutical classification system（BCS）is a scientific framework system which classifies the drugs according to their permeability and solubility.BCS is significant in promoting the development of new drugs,demonstrating the in vitro and in vivo correlation of drugs and applying the exemption of oral equivalent bioequivalence test.In this study,ducks were selected as the animal model.The solubility and permeablility of TAP and FFC were firstly studied to preliminary determine their BCS classification.At the same time,we also analyzed the absorption characteristics of TAP and FFC in duck intestine using everted intestinal sac model.The pharmacokinetics of TAP and FFC in duck was also studied,and the pharmacokinetic parameters and bioavailability data were obtained,hoping to provide theoretical basis for guiding clinical medication.Analysis and comparison the results of in vitro solubilty,permeability andeverted intestinal sac tests with the in vivo bioavailability,expecting to establish in vitro platform for BCS classification of oral preparation in duck.The classical shake flask method was applied to detemine the solubility of TAP and FFC at different pH and the everted intestinal sac model was used to study the in vitro permeability of TAP and FFC.The results indicated that TAP and FFC can dissolve in different pH（2.5,4.0,4.3,6.5,6.8,7.6）.On permeability aspect,different concentrations TAP and FFC can be absorbed in different duck intestinal section,the apparent permeability coefficient of small intestine is less than 10×10^-6 cm/s.Jejunum is the main apart to absorpt TAP and FFC.According to the guiding principle of FDA about BCS,thiamphenicol and florfenicol are BCS classⅢ.The pharmacokinetic behaviors of TAP and FFC in ducks were studied through single oral and intravenous administration.The pharmacokinetics of TAP in ducks after intravenous administration（10 mg/kg b.w.）were in line with a two-compartment open model.The T_1/2αis0.053±0.033 h,V_（c）is 0.694±0.017 L/kg,t_1/2βis 0.755±0.008 h,and CL_（S）is 1.220±0.007 L/kg/h.The pharmacokinetics of TAP in ducks after oral administration（10 mg/kg b.w.）fitted a one-compartment open model with first-order obsorption,the peak blood concentration（2.775±0.011μg/mL）at 0.559±0.007 h after administration,and the t_1/2ka is 0.167±0.004 h,t_1/2ke/2ke is 1.239±0.015 h,CL/F_（S）is 1.475±0.011 L/kg/h and bioavailability is 82.754±0.826%.The pharmacokinetics of FFC in ducks after intravenous administration（30 mg/kg b.w.）was found to be a two-compartment open model.The T_1/2αis 0.066±0.035 h,V_（c）is 1.105±0.194 L/kg,t_1/2βis 0.701±0.058 h,and CL_（S）is 1.684±0.032 L/kg/h.The pharmacokinetics of FFC in ducks after oral administration（30 mg/kg b.w.）concordant with a one-compartment open model with first-order obsorption,the peak blood concentration（7.491±0.130μg/mL）at 0.499±0.011 h after administration,and the t_1/2ka is 0.161±0.009 h,t_1/2ke is 0.967±0.054 h,CL/F_（S）is 2.009±0.060L/kg/h and bioavailability is 83.902±2.978%.The results indicated that TAP and FFC can be absorbed rapidly,distributed widely,eliminated quickly and have a high bioavailability after oral administration in ducks.The bioavailability of TAP and FFC in ducks was 82.754±0.826%和83.902±2.978%,respectively.TAP and FFC were low permeability drugs according to the classification standards of FDA permeability.The results were in accordance with the in vitro permeability test results of TAP and FFC,indicating that the permeability test results of TAP and FFC in vitro were in good correlation with in vivo.It is hoped that the in vitro intestinal permeability test will replace the bioequivalence test of duck drugs.