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作 者 ：张恒义,吕良,丛琳琳

期 刊 ：中国中药杂志 2010年 35卷 8期 页码：1064.

关键词：微透析；高效液相色谱；药动学；生物利用度；丹参素；

Keywords:microdialysis, HPLC, pharmacokinetics, bioavailability, Danshensu,

摘 要 ：目的: 应用自由活动大鼠颈静脉微透析实验技术研究丹参素在大鼠体内的药代动力学参数。 方法 :10只SD大鼠随机分为2组,每组5只,在右颈外静脉植入微透析导管,术后恢复3 d。从导管将微透析探针插入上腔静脉并平衡30 min后,按40 mg·kg^-1单剂量静脉注射或灌胃丹参素后采集透析液,用HPLC紫外检测器分析透析液中丹参素的含量,换算成血药浓度,并计算药动学参数。 结果 :静脉注射组丹参的药动学参数:终末段消除半衰期t_1/2zeta为(69.62±33.42) min,药-时曲线下面积AUC_0-∞为(3 416.24±779.80) mg·min^-1·L^-1,平均滞留时间MRT_0-∞为(38.15±8.61) min。灌胃组相应的药动学参数:C_max为(7.42±3.08) mg·L^-1,t_max为(31.50±8.57) min, t_1/2zeta为(83.25±37.35) min, AUC_0-∞(793.19±101.32) mg·min^-1·L^-1, MRT_0-∞为(125.89±58.270) min;生物利用度F为22.56%。 结论 :自由活动大鼠颈静脉微透析技术结合高效液相色谱分析可有效分析丹参素血药浓度,获得药-时曲线,提示该技术较适合于采用小动物对长时程连续用药中药活性成分进行药动学研究。

Abstract:Objective : To investigate the pharmacokinetics of Danshensu with in vivo microdialysis in freely moving rat‘s jugular vein. Method : three days after a microdialysis probe introducer was implanted into the jugular vein, a microdialysis probe was introduced to the blood vessel, and began to sample following a single intravenous injection (40 mg·kg^-1) or a single oral dose (40 mg·kg^-1) of Danshensu . All the samples were analyzed with HPLC. The concentration of Danshensu in blood were calculated according to the recovery of microdialysis probe and the concentration in dialysates. Pharmacokinetic parameters were than calculated with the concentration-time curve. Result: For intravenous administration, t_1/2zeta=(69.62±33.42) min, AUC_0-∞=(3416.24±779.80) min·mg·L^-1, MRT_0-∞=(38.15±8.61) min, and for oral administration, C_max=(7.42±3.08) mg·L^-1, t_max=(31.50±8.57) min, t_1/2zeta=(83.25±37.35) min, AUC_0-∞=(793.19±101.32) min·mg·L^-1, MRT_0-∞=(125.89±58.27) min. The oral bioavailability of Danshensu F=22.56%. Conclusion : In vivo microdialysis in freely moving rat‘s jugular vein is a useful tool to obtain a complete set of free drug concentrations to determine reliable pharmacokinetic parameters.

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