苄丝肼对大鼠纹状体细胞外液左旋多巴药动学的影响

目的探讨苄丝肼对左旋多巴大鼠纹状体细胞外液药动学影响。方法大鼠随机分3组（每组7只）：左旋多巴合并苄丝肼组，大鼠灌胃给予左旋多巴48mg·kg^-1和苄丝肼12mg·kg^-1；单用左旋多巴组，大鼠灌胃给予左旋多巴48mg·kg^-1；生理盐水对照组，大鼠灌胃给予等体积生理盐水。采用脑微透析活体取样和高效液相色谱技术，测定给药后6h内不同时间点大鼠血浆和纹状体细胞外液左旋多巴浓度，应用3P87药动学程序拟合药动学参数。结果左旋多巴在血浆及纹状体细胞外液药-时曲线符合一室模型。单用左旋多巴在纹状体细胞外液t1/2、tmax、ρmax和AUC0→∞分别为（21．55±13．74）min、（46．82±27．49）min、（9．283±2．130）μg·L^-1、（2762±1257）μg·L^-1；左旋多巴合用苄丝肼组纹状体细胞外液t1/2、tmax、ρmax和AUC0→∞分别为（83．50±10．24）min、（49．97±11．72）min、（119．62±81．12）μg·L^-1、（18431±9115）μg·L^-1。其中，除tmax外，单用左旋多巴组t1/2、ρmax和AUC0→∞均显著小于左旋多巴合用苄丝肼组（P〈0．01）。结论苄丝肼可显著提高左旋多巴进入纹状体药量。

Effects of benserazide on levodopa pharmacokinetics of extracellular fluids of striatum in rats

AIM To investigate the effect of benserazide on levodopa（LD） pharmacokinetics of extracellular fluids of striatum in rats. METHODS The rats were divided randomly into three groups： Group 1 （ n = 7）, LD 48 mg·kg^-1 and benserazide 12 mg·kg^-1 ,i.g. ; Group 2（n = 7）,LD 48 mg·kg^-1 i.g. ; Group 3（n = 7）, control group, 0.9% NaCl, i. g. Using brain microdialysis and high-performance liquid chromatography, the blood and microdialysis samples were collected at time intervals up to 6 hours, and the concentration of LD in plasma and brain extracellular fluids were determined at each time point. The data were dealt with 3P87 program by computer. RESULTS Both the plasma and striatal concentration-time profiles of LD were discribed by a one compartment model. The pharmacokinetic parameters of t1/2、tmax,AUC0→∞and ρmax in striatum of LD group were （21.55 ± 13.74）min, （46.82 ± 27.49）min, （9.283 ± 2. 130） μg·L^-1and （2 762 ± 1 257）μg·min·L^-1, respectively; while in LD ± benserazide group they were（83.50 ± 10.24） rain, （49.97 ± 11.72） min, （ 119.62 ± 81.12） μg·L^-1 and （ 18 431 ± 9 115）μg·min·L^-1, respectively. Among these parameters, t1/2 ,AUC0→∞ and ρmax were much higher in LD ± benserazide group than those in LD group（ P 〈 0.01） except tmax CONCLUSION Benserazide can increase the amount of LD entering extraeellular fluids of striatum greatly.