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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48mg.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(t1/2)、达峰时间(tm ax)、达峰浓度(mρax),药-时曲线下面积(AUC0→∞)分别为(63.25±25.80)m in,(34.21±8.70)m in,(112.98±76.85)μg.L-1,(14 443±8 744)μg.m in.L-1(n=7),血浆t1/2,tm ax,ρm ax,AUC0→∞分别为(78.94±7.95)m in,(6.763±3.579)m in,(4 373±1 815)μg.L-1,(509 940±134 619)μg.m in.L-1(n=7),其中左旋多巴在纹状体细胞外液和外周血t1/2相近(P>0.05),而纹状体tm ax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。
Objective To investigate the regularity of levodopa in blood and striatum extracellular fluid concentration in rats over time. Methods After intragastric administration of 48 mg · kg-1 levodopa and 12 mg · kg-1 of benserazide by single intragastric administration, brain microdialysis and high performance liquid chromatography (HPLC) The plasma and striatum extracellular concentrations of levodopa in rat plasma were determined. Pharmacokinetic parameters were fitted using the 3P87 pharmacokinetic program. Results The levodopa in the plasma and striatum extracellular fluid-time curves were in line with a one-compartment model, levodopa in striatal extracellular fluid half-life (t1 / 2), the peak time (tm ax), peak (63.25 ± 25.80) mins, (34.21 ± 8.70) mins, (112.98 ± 76.85) μg.L-1, (14 443 ± 8) (78.94 ± 7.95) mins, (6.763 ± 3.579) mins, (4) and (4) 373 ± 1815) μg.L-1 and (509 940 ± 134 619) μg.m in.L-1 (n = 7), respectively, in which levodopa was similar to t1 / 2 in peripheral blood of striatal cells (P> 0.05), whereas striatum tm ax was much larger than that of peripheral blood (P <0.01). Conclusion The concentration of levodopa in the blood and the target site of the striatum varies with time. The change of plasma concentration can not fully reflect the change of the drug in the brain.