应用微透析研究盐酸川芎嗪大鼠腹腔给药后脑和血中的药动学特征  

Brain and blood pharmacokinetics of tetramethylpyrazine hydrochloride after intraperitoneal administration in rats by microdialysis

作　　者：徐红燕[1,2] 汤湛[1] 王俏[1] 

机构地区：[1]浙江省医学科学院药物研究所,杭州310013 [2]浙江省台州市中心医院药剂科,台州318000

出　　处：《中国临床药学杂志》2013年第4期206-211,共6页Chinese Journal of Clinical Pharmacy

基　　金：浙江中医局(编号2012ZA024);浙江省自然科学基金(编号LY12H29011);浙江省医学重点学科群(编号XKQ-010-001);浙江省科技计划(编号2011F10048);浙江省卫生高层次创新人才培养工程(编号XKQ010012008)

摘　　要：目的研究大鼠腹腔注射盐酸川芎嗪后川芎嗪在血、脑中的药动学差异,并比较两个剂量给药后的药动学参数。方法以川芎嗪为检测药物,HPLC法测定不同时间点大鼠血浆和脑、血管微透析液中的川芎嗪含量,DAS 2.0药动学软件计算药动学参数。结果大鼠腹腔注射给药后,川芎嗪在大鼠体内吸收、分布迅速,消除较快,体内各部位药动学情况符合二室模型。体内药物含量以血浆中最高,血微透析次之,脑微透析最低。20mg·kg^(-1)腹腔注射后的AUC_(脑微透析)/AUC_(血微透析)、AUC_(脑微透析)/AUC_(血浆)、AUC_(血微透析)/AUC_(血浆)分别为64.9%、29.9%、46.2%;40 mg·kg^(-1)腹腔注射给药后的相应比值分别为68.3%、30.6%、45.0%,两个剂量的相应AUC比值之间差异无统计学意义(P>0.05)。结论血、脑微透析法与血浆法测得的药动学对比,能较好地反映体内游离药物的药动学特征,为I临床用药提供可靠的理论依据。AIM To investigate and compare the pharmacokinetic characteristics of tetramethylpyrazine hydrochlo- ride（TMPH） in brain microdialysate, blood microdialysate and plasma of two dosages after intmperitoneal （ip） adminis- tration in rats. METHODS The concentrations of tetramethylpyrazine （TMP） were determined by HPLC while the phar- macokinetic parameters were calculated by DAS 2.0 software. RESULTS The concentration-time profiles met two-com- partment model. The distribution and elimination of TMP were quick and extensive. The concentration of TMP in plasma was higher than that in blood microdialysate, and the latter was higher than that in brain microdialysate （ P 〈 0.01 ）. The ratios of AUCbrain MD/AUCblood MD, AUCbrain MD/AUCplasma and AUCblood MD/AUCplasma were 64.9%, 29.9% and 46.2% respectively after ip administration of 20 mg-kg-1 TMPH in rats, while the ratios of them were 68.3%, 30.6% and 45.0% respectively after ip administration of 40 mg＇kg-1TMPH. There were no significant differences （ P 〉 0.05） between the homologous ratios in two dosages. CONCLUSION The microdialysate technology is an appropriate study tool which could show pharmacokinetic characteristics after ip administration of TMPH. And it would also provide a reliable theoretical basis for clinical medication.

关 键 词：微透析 川芎嗪 药动学 腹腔注射 

分 类 号：R285.5[医药卫生—中药学]