左旋多巴在大鼠外周血及纹状体细胞外液中的药动学研究

Pharmacokinetic study on levodopa in rats blood and extracellular fluids of striatum

目的:探讨左旋多巴(LD)在大鼠外周血及纹状体细胞外液中的药动学行为。方法:大鼠随机分为2组,按高、低剂量单次灌胃给予多巴丝肼(LD+苄丝肼),采用脑微透析技术采集纹状体细胞外液透析液,并于对应时间点采集外周血,高效液相色谱-电化学(HPLC-ECD)法测定透析液及血浆LD浓度,应用3P97药动学软件拟合药动学参数。结果:外周血及纹状体细胞外液中LD药-时曲线符合一室模型。纹状体细胞外液相对于外周血LD达峰时间(tmax)延迟,峰浓度(Cmax)及药-时曲线下面积(AUC0→∞)显著减小,半衰期(t1/2)接近。LD通过血脑屏障进入纹状体的比值约2%～3%。结论:大鼠外周血及纹状体细胞外液中的LD浓度与给药剂量呈正相关。2种环境中LD浓度在一定程度上具有相关性,但其变化规律并不一致。纹状体细胞外液的LD药动学过程与外周血相比存在时间滞后,血药浓度变化不能完全反映LD在纹状体细胞外液中的药动学行为。

OBJECTIVE To investigate the pharmacokinetic profiles of levodopa in plasma and extracellular fluids in striatum of rats. METHODS SD rats were randomly divided into 2 groups： high dose group and low dose group. Dialysates were collected using microdialysis after intragastric administration of levodopa and benserazide,and blood samples were drawn simultaneously. Concentration of levodopa in dialysates and plasma were determined by HPLC ECD. The data were analyzed with 3P97 program. RESULTS Both the plasma and striatal concentration-time profiles of levodopa were described by one compartment model. In striatum, Cmax and AUC0→∞ of LD was significantly smaller and tmax was significantly longer than that in plasma （P〈 0. 05）,While t1/2 in striatum was similar with that in plasma （P〉0. 05）. The approximate ratio of levodopa in striatum and in plasma was 3%. CONCLUSION There was a positive association between dosage and concentration of levodopa in striatum and plasma. There were differences in pharmacokineties of levodopa between striatum and plasma. The pharmacokinetics of ievodopa in striatum lagged behind that in blood. The pharmacokinetics of levodopa in blood can not reflect completely that in striatum.