左旋多巴在大鼠血液和纹状体细胞外液中的药动学行为

 目的 探讨左旋多巴在大鼠血液和纹状体细胞外液药物浓度随时间变化规律。方法 大鼠单次灌胃给予左旋多巴48 mg·kg-1和苄丝肼12 mg·kg-1后，采用脑微透析活体取样和高效液相色谱技术，测定给药后6 h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-时曲线均符合一室模型，左旋多巴在纹状体细胞外液半衰期（t_1/2）、达峰时间（t_max）、达峰浓度（ρ_max），药-时曲线下面积（AUC_0→∞）分别为（63.25±25.80） min， （34.21±8.70）min，（112.98±76.85）μg·L-1，（14 443±8 744）μg·min·L-1（n=7），血浆t_1/2，t_max，ρ_max，AUC_0→∞分别为（78.94±7.95） min， （6.763±3.579) min， （4 373±1 815）μg·L-1，（509 940±134 619）μg·min·L-1（n=7），其中左旋多巴在纹状体细胞外液和外周血t_1/2相近（P>0.05），而纹状体t_max远大于外周血（P<0.01）。结论 左旋多巴在血液和作用靶部位纹状体药物浓度随时间变化不完全一致，血药浓度变化规律不能完全反映药物在脑内变化情况。

Pharmacokinetics of Levodopa in Rat Blood and Extracellular Fluids of Striatum

OBJECTIVE To investigate the pharmacokinetic profiles of levodopa in plasma and extracellular fluids in striatum of rats. METHODS Samples were collected using microdialysis after intragastrical administration of levodopa 48 mg·kg-1 and benserazide 12 mg·kg-1. The blood and microdialysis samples were collected up to 6 h，and the concentration of levodopa in plasma and brain extracellular fluids were determined by high-performance liquid chromatography. The data were analyzed with 3P87 program. RESULTS Both the plasma and striatal concentration-time profiles of levodopa were described by a one compartment mode1. The pharmacokinetic parameters of t_1/2， t_max， ρ_max and AUC_0→∞ in striatum were （63.25±25.80） min， （34.21±8.70）min， （112.98±76.85）μg·L-1 and （14 443±8 744）μg·min·L-1（n=7） , respectively， while the parameters in plasma were（78.94±7.95）min， （6.763±3.579）min，（4 373±1 815）μg·L-1 and （509 940±134 619）μg·min·L-1（n=7）, respectively. Among these parameters， t_1/2 in striatum was similar with that in plasma （P>0.05）， while t_max in striatum was significantly different from that in plasma（P<0.01）. CONCLUSION There were differences on pharmacokinetics of levodopa between striatum and plasma.