Study On Pharmacokinetics Of Combination Of Cefotaxime Sodium And Probenecid Sodium In Rabbits

Objective:(1)To investigate and evaluate the stability and safety of Cefotaxime Sodium and Cefotaxime Sodium-Probenecid Sodium mixed powder for injection;(2)Establish analysis method of Cefotaxime Sodium in rabbit plasma;(3) Study the pharmacokinetics dynamics of Cefotaxime Sodium in healthy rabbits influence by Probenecid Sodium. Methods:(1)Study the stability and safety of Cefotaxime Sodium and Cefotaxime Sodium-Probenecid Sodium mixed powder for injection by influencing test、 accelerated test and safety test;(2)Eastablish the method of Cefotaxime Sodium in plasma by high performance liquid chromatography (The processing method of plasma、 condition optimization of chromatographic) and verify its analysis method.(3) Select the experimental rabbits and randomly divided into5groups, which have4in a group. Control group:Inject the Cefotaxime Sodium into deep intramuscular of rabbit leg by the dosage of50mg/kg; Experimental group:Inject the Cefotaxime Sodium-Probenecid Sodium into deep intramuscular of rabbit leg (measured by the Cefotaxime Sodium in50mg/kg dosage). Eastablish the method of Cefotaxime Sodium in plasma by high performance liquid chromatography and calculate the pharmacokinetic parameters by3p97pharmacokinetic program. Results:(1)The Cefotaxime Sodium and Cefotaxime Sodium-Probenecid Sodium mixed powder for injection were good stability out of heat (4℃) and light; Both products were in little toxicity and intramuscular irritation;(2) The method between0.2-80mg/L has a fine linear relation, regression equation: y=22300x+1446.1(R2=0.9994), the lowest detection of Cefotaxime Sodium in rabbit plasma was0.005mg/L, the quantitative was0.002mg/L, the average recovery rate was between97.2%-99.6%, above all were fully meet the requirements of biological sample analysis;(3) The pharmacokinetic data by inject Cefotaxime Sodium and Cefotaxime Sodium-Probenecid Sodium mixed powder into rabbits were in accordance with the level one chamber absorption model, the fitting equation were: C＝66.4017e-0.5828t-66.1027e-19.2970t C=65.6338e-0.3133t-65.6338e-18.6897t C=67.5679e-0.4325t-67.5679e-18.1940t C=67.2408e-0.4995t-67.2408e-19.5226t C=67.4310e-0.5698t-67.4310e-19.3595t;(4) While the Cefotaxime Sodium and Probenecid Sodium were in equal proportion has the most significant effect on the pharmacokinetics in rabbits. The main pharmacokinetics parameters for injection of Cefotaxime Sodium-Probenecid Sodium mixed powder(Pharmacokinetics parameters for single injection of Cefotaxime sodium):half-life of elimination (tl/2):2.2245±0.1952h (1.1912±0.0569);Area under the curve(AUC):(204.5569±12.5594)mg·L-1·h (110.6734±5.9405);The peak plasma concentration(Cmax):(60.8243±0.8886)mg·L-1(57.7359±1.1494); Plasma clearance (CL/F):(0.6384±0.0538)L·h-1(1.1446±0.0515);The statistically significant difference between the above all are highly significant(P<0.01). Conclusion:(1)The Cefotaxime Sodium and Cefotaxime Sodium-Probenecid Sodium mixed powder for injection should be stored in shade, the clinical dosage is safe and fit for muscle injection;(2) The analysis methodof Cefotaxime Sodium in rabbit plasma has high plasma separation degree、 high recovery rate、 good repeatability and can be used for study of Cefotaxime Sodium metabolism dynamics in vivo rabbits;(3) Add Probenecid Sodium into Cefotaxime Sodium can decrease the vivo elimination rate significantly, prolong the half-life of elimination, improve the bioavailability, and when the ratio between Cefotaxime Sodium and Probenecid Sodium is1:1, there was the most significant effect.