Synchronous Pharmacokinetics Study on Effects of Shouwu Fang on Levodopa in Blood and in Extracellular Fluids of Striatum in Rats with Parkinson’s Disease

SUN Xiao-fang; WANG Dan-qiao; WU Zhao-en; LI Peng; NIU Jian-zhao; WANG Ji-feng; WANG Wei

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Synchronous Pharmacokinetics Study on Effects of Shouwu Fang on Levodopa in Blood and in Extracellular Fluids of Striatum in Rats with Parkinson’s Disease

更新时间：2024-01-04

- Synchronous Pharmacokinetics Study on Effects of Shouwu Fang on Levodopa in Blood and in Extracellular Fluids of Striatum in Rats with Parkinson’s Disease
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 17, Issue 11, Pages: 111-115(2011)
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- Published：2011
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SUN Xiao-fang, WANG Dan-qiao, WU Zhao-en, et al. Synchronous Pharmacokinetics Study on Effects of Shouwu Fang on Levodopa in Blood and in Extracellular Fluids of Striatum in Rats with Parkinson’s Disease[J]. Chinese journal of experimental traditional medical formulae, 2011, 17(11): 111-115.
DOI：

SUN Xiao-fang, WANG Dan-qiao, WU Zhao-en, et al. Synchronous Pharmacokinetics Study on Effects of Shouwu Fang on Levodopa in Blood and in Extracellular Fluids of Striatum in Rats with Parkinson’s Disease[J]. Chinese journal of experimental traditional medical formulae, 2011, 17(11): 111-115. DOI：

摘要

目的: 采用清醒自由活动大鼠血-脑双位点微透析采样的方法

同步探讨首乌方对左旋多巴(L-DOPA)在帕金森病(PD)大鼠血液和纹状体细胞外液药动学的影响。方法: SD大鼠分为4组

对照组、模型组、左旋多巴组、首乌方+左旋多巴组。脑内注射6-羟基多巴胺(6-OHDA)造模

首乌方＋左旋多巴组提前ig首乌方煎剂(生药量18 g ·kg-1 ·d-1)6 d

各给药组单次ip L-DOPA 24 mg ·kg-1和盐酸苄丝肼6 mg ·kg-1。血-脑双位点微透析采样

分别用高效液相-荧光法(HPLC-FLD)、高效液相-电化学法(HPLC-ED)检测血液、纹状体细胞外液L-DOPA浓度。应用DAS软件拟合药动学参数。结果: 与左旋多巴组相比

首乌方+左旋多巴组血药浓度在6个时间点升高

纹状体细胞外液药物浓度在给药后15 min时降低(P<0.05)。左旋多巴组、首乌方+左旋多巴组血液药动学参数分别为:AUC(1 627.7±420.6)mg ·L-1 ·min-1

(2 626.4±980.6) mg ·L-1 ·min-1;Tmax30 min

(37.5±8.2)min

MRT(0-t) (71.98±3.19) min

(83.44±9.53) min。纹状体细胞外液药动学参数分别为:Tmax(50.0±15.5) min

(81.0±27.3) min

MRT(0-t) (68.7±15.34)min

(107.9±26.7)min。与左旋多巴组相比

首乌方+左旋多巴组血液AUC增加(P<0.05)

Tmax延后(P<0.05)

MRT(0-t)延长(P<0.05)。纹状体细胞外液Tmax滞后(P<0.05)

MRT(0-t)延长(P<0.05)。结论: 首乌方可减慢L-DOPA消除

增加血液L-DOPA的吸收

减少纹状体L-DOPA药物浓度波动。

Abstract

Objective: To synchronously investigate the effects of Shouwu Fang on the pharmacokinetics of levodopa (L-DOPA) in blood and in extracellular fluids of striatum in rat with Parkinson’s disease (PD)

by simultaneous blood-brain microdialysis in freely moving rats. Method: SD rats were randomly divided into four groups:control group

model group

L-DOPA group (ip L-DOPA 24 mg ·kg-1and benserazide 6 mg ·kg-1)

SWF+L-DOPA group (ip L-DOPA pretreated with ig SWF).The rat model of Parkinson’s disease was induced by injecting 6-hydrodopamine (6-OHDA) into striatum of rats

blood-brain microdialysis technique was used for simultaneously sampling.High performance liquid chromatography-fluorescence detector (HPLC-FLD) and high performance liquid chromatography-electrochemical detector (HPLC-ED) were used to detect the concentration of L-DOPA in blood and striatum.The data were analyzed with DAS program. Result: Compared with L-DOPA group

the blood L-DOPA concentration of SWF+L-DOPA group was increased significantly at 6 time points

the concentration in striatum was decreased at 15 min after drug administration.The blood pharmacokinetic parameters of L-DOPA group and SWF+L-DOPA group were as follows:AUC(1 627.7±420.57) mg ·L-1 ·min-1

(2 626.44±980.6) mg ·L-1.min-1

Tmax:30 min

(37.5±8.22) min

MRT(0-t);(71.98±3.19) min

(83.44±9.53) min

striatum pharmacokinetic parameters:Tmax:(50±15.49) min

(81±27.25) min

MRT(0-t);(68.65±15.39) min

(107.91±26.66) min.Compared with L-DOPA group

SWF+L-DOPA group blood AUC was increased (P<0.05)

Tmaxand MRT(0-t) were delayed (P<0.05);striatum Tmaxand MRT(0-t) were delayed too (P<0.05). Conclusion: Shouwu Fang delayed L-DOPA elimination

increased its absorption in blood

and reduced fluctuation of concentration in striatum.

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