Research On Compound Amoxicillin Injectional Suspension And Study On Its Pharmacokinetics In Healthy Rats

Objective:The aim of this study was to evaluate the antibacterial activity of Borneol combined with Amoxicillin against clinical isolated of Staphylococcus aureus, Staph-ylococcus epidermidis and E.coli in vitro,and to develop New Amoxicillin infectional suepension designed mainly for Borneol and Amoxicillin,and to study the effect of Borneol on pharmacokinetics of Amoxicillin in rats and distribution in brain after intramuscular injection(im).Methods:The MIC(minimaL inhibitory concentration,MIC) determination of Amoxicillin,Borneol,and Borneol combined with Amoxicillin were performed with the method of solid medium continuously dilution respectively.The FIC(fractiona inhibitory concentration index)was determined with checkerboard system,and the optimun prescription was gained by orthogonal design.Meanwhile,the hemolytic test,light & heat stability test and muscular irritation tset were carried out.24 healthy Wistar rats were alllocated into 2 groups of 12 rats at random.The rats in groupâ… were im given with single dose of Amoxicillin infectional suspension at 200(kg·b·w).The rats in groupâ…¡were im given with single dose of New Amoxicillin infectional suspension at 200(mg/kg·b·w).Results:In combination,the MIC of Amoxicillin and Borneol against Staphylococcusaureus and Staphylococcus epidermidis both decreased to 1/8 of the former MIC.The FIC of both was 0.25.And NO.9 was the optimum description under comprehensive marking that included 3.0%suspension agent,2.0%wetting agent and 2.5%antioxidant.The tests indicated that New Amoxicillin performed moderate irritation,no hemolytic reaction in 15min～3h and conformed to stability regulation.The model were fitted-a two-compartment model with 1st order absorption(weight=1/C²).The main pharmacokinetics parameters and calculated-equations in chickens were as follows, respectively:T_1/2Ka=(0.13±0.002)h,T_1/2α=(3.918±0.022)h,T₁/2β)=(38.024±0.016)h,T_peak=(0.754±0.000)h,C_max=(41.150±0.058)mg/L,A UC=(254.653±0.019)(mg/L·h),Ka=(8.297±0.059)(1/h), V1/F=(7.847±0.090)L/kg,CL/F=(0.648±0.069)L/h/kg,C=2.256e^-1.389t+0.737e^-0.048t-2.993e^{-18.5 06t}.Groupâ…¡:T_1/2Ka=(0.048±0.052)h,T_1/2α=(2.795±0.000)h,T_1/2β=(48.892±0.064)h,T_peak=(0.75±0.000)h,C_max=(37.960±0.026)mg/L,A UC=(242.646±0.011)(mg/L·h),Ka=(14.424±0.051)(1 / h),V 1/F=(5.567±0.017)L/kg,CL/F=(0.711±0.012)L/h/kg,C=2.256e^-1.389t+0.737e^-0.048t-2.993 e^-18.506t.Conclusion:Borneol combined with Amoxicillin showed synergistic effect against Staphylococcus aureus and Staphylococcus epidermidis.But it showed no synergistic effecta gainst E.coli.New Amoxicillin infecional suspension conformed to all the tests and could be used clinically.Borneol could influend the pharmacokinetic variables of Amoxicillin in healthy rats significantly:accelerated the speed of absorption;accelerated the distribution from blood to brain;retarded the speed of elimination,increased the time of drug action;When New Amoxicillin was im administered,the Amoxicillin concentration of brain tissue in healthy rats increased notably.It was likely that Borneo could enhance the permeation of Amoxicillin to brain,and this provided experiment basis for Chinese traditional medicine guiding drug theory and combination application of Chinese and western in veterinary drug.