银杏叶提取物含药血清在大鼠体内药动学与药效学相关性研究

A study on the correlation between the pharmacodynamic and pharmacokinetic characteristics of serum containing Ginkgo biloba extract in rats

目的以银杏叶提取物对肾小球系膜细胞氧化损伤的保护作用为药效指标,研究银杏叶提取物中5种黄酮类成分(芦丁、槲皮苷、槲皮素、山奈酚及异鼠李素)的体内药动学及药效学过程的相关性。方法大鼠静脉给药后,测定不同取血时点血清样本中5种黄酮类成分的含量,运用血清药理学方法,观察不同时间点血清样本及银杏叶提取物对高糖诱导大鼠肾小球系膜细胞氧化损伤的保护作用,对浓度-时间、效应-时间曲线进行相关分析,建立药动-药效结合模型。结果银杏叶提取物含药血清对大鼠肾小球系膜细胞氧化损伤有明显保护作用,且血清中芦丁、槲皮苷、山奈酚及异鼠李素的药理效应的达峰时间(peak tim e,Tpeak)与药动学曲线下面积(areaunder the curve,AUC)的Tpeak一致。结论银杏叶提取物体内、外均具有抗氧化作用,且效应的时效关系与血清中芦丁、槲皮苷、山奈酚及异鼠李素的时量关系呈正相关。

Objective To investigate the correlation between the pharmacokinetic and pharmacodynamic processes of Ginkgo biloba extract （ GBE）, with the protective effect of GBE on the oxidative injury of glomerular mesangial ceils as the pharmacodynamic index. Methods Following intravenous administration of GBE in rats, the drug - containing serum was obtained at different time points and each sample was divided into two portions. One portion was added into the cultured rat mesangial cells, which had been treated with 25 mmol/L glucose, for the determination of the activities of cell antioxidases by spectrophotometry. The other was used to determine the concentration of the 5 flavones （ rutin, quercetrin, quercetin, kaempferol and isorhamnetin）. Thus the pharmacokinetics -pharmacodynamics model among concentration, time and effect was established. Furthermore, the effect of GBE was also investigated in vitro. Results Marked antioxidant effects of GBE and drug - containing serum could be demonstrated by in vitro tests. The peak time in the pharmaeodynamic curves of rutin, quercetrin, kaempferol and isorhamnetin was consistent with that of the pharmacokinetic area under the curve （AUC） after intravenous administration. Conclusion The protection effect of the GBE - containing serum had positive time - effect and time concentration correlations with the AUC of rutin, quercetrin, kaempferol, and isorhamnetin in serum.