Li Y, Pan W S, Chen S L, Xu H X, Yang D J, Chan A S C
School of Pharmacy of Shenyang Pharmaceutical University, Shenyang 110016, China.
Drug Dev Ind Pharm. 2006 Apr;32(4):413-22. doi: 10.1080/03639040600559123.
Puerarin is a potential therapeutic agent for cardiovascular diseases. But its poor oral bioavailability restricts its clinical application. In present study, as an evaluation of a formulation to improve the bioavailability of the drug, puerarin and its phospholipid complex were given to rats by intragastrically (i.g.) administration to compare pharmacokinetic, tissue distribution, and excretion. Serum samples were obtained at designated times after a single oral dose of 400 mg/kg puerarin or its complex. Tissue samples (heart, liver, spleen, kidney, lung, and brain), urine, and feces were collected and analyzed by a sensitive and specific high performance liquid chromatography (HPLC) method after i.g. administration of puerarin or its phospholipid complex. Compartmental and non-compartmental analyses were applied to the serum concentration versus time data. Pharmacokinetic parameters were calculated using the 3P97 pharmacokinetic software package. An open two-compartment, first-order model was selected for pharmacokinetic modeling. The results showed that after i.g. administration of 400 mg/kg puerarin and its phospholipid complex (equivalent to 400 mg/kg of puerarin), the pharmacokinetic parameters of the two formulations were different. The serum concentrations reached peaks at 0.894+/-0.521 h and 0.435+/-0.261 h, respectively, indicating the complex was more readily absorbed in serum than puerarin. The maximum concentrations for puerarin and its complex were 1.367+/-0.586 mg.L(-1) and 2.202+/-1.28 mg.L(-1) and AUC were 5.779+/-1.662 mg.h. L(-1) and 8.456+/-0.44 mg.h L(-1), respectively, indicating a higher bioavailability for the complex. The widely distribution characteristics of puerarin and its complex in tissues post-i.g. administration was identical and in a descending order as follows: lung, kidney, liver, heart, spleen, and brain. However, the amount was different. Puerarin distribution was higher in heart, lung, and brain after administering the complex. The cumulative 72 h urinary excretion of puerarin after i.g. administration of puerarin and its complex accounted for 1.05%, 1.11% of the administered dose, respectively. The cumulative feces excretion of puerarin was 32.3% and 25.5%. To sum up, oral administration of puerarin phospholipid complex modified the pharmacokinetics and tissue distribution of puerarin and it could be an effective oral formulation for puerarin.
葛根素是一种潜在的心血管疾病治疗药物。但其口服生物利用度较差，限制了其临床应用。在本研究中，作为对一种改善药物生物利用度制剂的评估，将葛根素及其磷脂复合物经胃内（i.g.）给药于大鼠，以比较其药代动力学、组织分布和排泄情况。单次口服400mg/kg葛根素或其复合物后，在指定时间采集血清样本。在i.g.给予葛根素或其磷脂复合物后，收集组织样本（心脏、肝脏、脾脏、肾脏、肺和脑）、尿液和粪便，并通过灵敏且特异的高效液相色谱（HPLC）法进行分析。对血清浓度-时间数据应用房室和非房室分析。使用3P97药代动力学软件包计算药代动力学参数。选择开放二室一级模型进行药代动力学建模。结果表明，i.g.给予400mg/kg葛根素及其磷脂复合物（相当于400mg/kg葛根素）后，两种制剂的药代动力学参数不同。血清浓度分别在0.894±0.521小时和0.435±0.261小时达到峰值，表明复合物比葛根素在血清中更易吸收。葛根素及其复合物的最大浓度分别为1.367±0.586mg·L⁻¹和2.202±1.28mg·L⁻¹，AUC分别为5.779±1.662mg·h·L⁻¹和8.456±0.44mg·h·L⁻¹，表明复合物具有更高的生物利用度。i.g.给药后葛根素及其复合物在组织中的广泛分布特征相同，降序排列如下：肺、肾、肝、心、脾、脑。然而，含量不同。给予复合物后，葛根素在心脏、肺和脑中的分布更高。i.g.给予葛根素及其复合物后，葛根素72小时的累积尿排泄量分别占给药剂量的1.05%、1.11%。葛根素的累积粪便排泄量分别为32.3%和25.5%。综上所述，口服葛根素磷脂复合物改变了葛根素的药代动力学和组织分布，它可能是一种有效的葛根素口服制剂。
