Pharmacokinetic Of Comparing Orally Naodesheng Microemulsion And Naodesheng Tablet

OBJECTIVESThe aim of this study is to compare Naodesheng bioavailability of oral microemulsion with tablet, after rats were given the same dose orally Naodesheng microemulsion and tablets, to provide the basis of Formulations design and the reasonableness evaluation of orally Naodesheng microemulsion.METHODS1. Experimental animals and drug delivery methods1.1Experimental animal grouping and dose in ratsHealthy adult male SD rats of clean grade144(180-220g) were selected and randomly divided into2groups and72rats per geoup:oral lyNaodesheng microemulsion group (A) and Naodesheng tablets group (B).The mode of administration:oral microemulsion and tablets are administered orally.Dose:oral microemulsion dose was1.8mL/(kg·d), tablet dose was1.08g/(kg·d).1.2Administration methods and sample collection The adaptability of rats were feeded for a week, fasted for12h before the experiment. After intragastric administration, respectively5,10,20,30,45min,1,1.5,2,4,6,8,12h bleeding5ml by removing the eyes,6rats at each time point in each group, heparin EP tubes for5ml were centrifugated in3000rpm for10min, preparation of plasma saved at-70℃.2. Determination of biological samples and data analysis2.1The HPLC method was used to determine the main active ingredient concentration (HSYA, Rg1, Puer and TMP) of Naodesheng in the plasma.2.2The pharmacokinetic formula of AUC0-12, AUC0～∞, Cmax,Tmax,t1/2, Ke, f tCdt, AUMC and MRT were edited and the data was processed by Excel statistical software; the plasma the AUCo-12, the AUC0～∞, Cmax, Ke and MRT of microemulsion and tablets was processed with the analysis of variance two-sample t-test by statistical software SPSS13.0, the plasma the Tmax and tmax of microemulsion and tablets was processed with the analysis of Wilcoxon rank sum test by statistical software SPSS13.0.RESULTS1. An HPLC method for the methodology of HSYA, Rg1, Puer and TMP in the plasmaThe separation effect and the linear relationship of HSYA, Rg1, Puer and TMP in the plasma within the concentration range of0.27～135,0.24～90,0.54～54,0.08-40μg·mL-1were well; The Minimum limit of quantification were respectively0.27,0.24,0.54and0.08μg.mL-1;The retention time of analytes were respectively8.68,8.26,6.03and6.44min； The plasma average extraction recoveries (RSD) were respectively (n=5)95.69%(2.7%),95.03%(2.5%),90.20%(1.5％)and93.54%(0.98％);The method recovery(RSD)were respectively(n=5)92.73％～99.34%(1.2%-6.9%),98.30%-98.92%(1.2%-1.7%),97.91%-99.01％(0.86%-1.4%)and99.21%～100.57%(1.1%～1.7%)； Intra-day precision were respectively both less than10.2%,4.42%,1.17%and3.30%；Inter-day precision were respectively both less than7.85%,4.60%,0.873％and1.48%;High,middle and low concentrations of Control samples was stable,concentration variations were respectively less than6.53%,4.75%,1.11%and0.32%.2.Pharmacokinetic of comparing orally Naodesheng microemulsion and Naodesheng tabletsThe rats AUC0-12plasma of the orally Naodesheng microemulsion HSYA,Rgl,Puer and TMP were respectively24.16±0.54.23.64±0.81.28.08±0.33�'�3.15±0.07μg·h·mL-1;AUC0-∞were25.79±0.99.25.23±0.66.34.01±0.72�'�3.26±0.07μg·h·mL-1;t1/2were2.96±0.30,3.38±0.30,3.84±0.16and3.14±0.29h;Cmax were respectively10.89±0.16.15.34±0.07.22.75±0.43�'�0.08±0.01μg·mL-1;MRT were respectively5.27±0.29.4.22±0.07.5.51±0.15and6.49±0.22h. The rats plasma AUC0-12of Naodesheng tablets HSYA,Rg1,Puer and TMP were respectively19.48±0.82,17.96±0.09,20.59±0.33and1.82±0.08μg·h·mL-1; AUC0-∞were respectively20.60±1.49,19.36±0.09,26.34±1.08and6.05±2.91μg·h·mL-1; t1/2were respectively2.68±0.54,3.51±0.07,2.45±0.11and3.14±0.23h; Cmax were respectively7.39±0.12,10.47±0.04,12.83±0.05and2.95±0.46μg·mL-1; MRT were respectively4.93±0.56,4.64±0.06,6.96±0.19and6.96±0.11h.CONCLUSIONS1. MethodologyThe experimental method can be accurate, rapid determination of the concentration of the rats plasma HSYA, Rg1, Puer and TMP to examine pharmacokinetic characteristics of orally Naodesheng microemulsion and tablets.2. Animal experimentsComparing orally Naodesheng microemulsion with tablets, the AUC0-12,AUC0-∞and Cmax of HSYA、Rg1、Puer、TMP were statistically significant increased (p<0.05), suggesting that the orally Naodesheng microemulsion can facilitate the absorption of HSYA、Rg1、Puer、TMP.