南方医科大学学报

南方医科大学学报 ›› 2016, Vol. 36 ›› Issue (04): 548-.

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吴茱萸碱羟丙基-β-环糊精分子包合物的药代动力学

张雪，刘宏明，雷婷婷，冯娇，张景勍   

  • 出版日期:2016-04-20 发布日期:2016-04-20

A preliminary study of pharmacokinetics of evodiamine hydroxypropyl-β-cyclodextrin inclusion complex

  • Online:2016-04-20 Published:2016-04-20

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摘要： 目的比较吴茱萸碱分子包合物与吴茱萸碱在大鼠体内药代动力学行为和特征。方法制备吴茱萸碱分子包合物，以吴 茱萸碱为对照，检测二者在水中的溶解度及体外累计释放百分率；大鼠尾静脉给予吴茱萸碱包合物以及游离吴茱萸碱后，HPLC 法测定血浆中吴茱萸碱的浓度。用DAS 2.1.1软件计算药动学参数及生物利用度。结果吴茱萸碱包合物在水中的溶解度约 为18 μg/mL、累计释放百分率约为80%，与游离吴茱萸碱相比都有很大的提高。吴茱萸碱包合物和游离吴茱萸碱在大鼠体内的 Cmax分别为252.5±12.43 μg/L和161.3±3.45 μg/L；Tmax分别为4.00 h和4.07 h；MRT0-∞分别为8.46±0.91 h和4.43±0.74 h；AUC0-t分 别为2266.40±28.64 μg·L-1·h-1和911.92±8.53 μg·L-1·h-1；AUC0-∞分别为2359.76±31.58 μg·L-1·h-1和919.16±9.73 μg·L-1·h-1；吴茱 萸碱包合物相对生物利用度256.73%。结论吴茱萸碱包合物明显改善了药物的药代动力学行为，提高了药物的生物利用度。

Abstract: Objective To compare the pharmacokinetic parameters of evodiamine hydroxypropyl-β-cyclodextrin inclusion complex and free evodiamine suspension in rats, and investigate the pharmacokinetic characteristics of evodiamine inclusion complex. Methods Both water solubility and cumulative release percentage of EHD were tested with evodiamine as the control. Blood samples were collected from the venous plexus of SD rats after intravenous administration with evodiamine inclusion complex and free evodiamine at 100 mg/kg (equivalent evodiamine dose). Plasma concentrations of evodiamine were determined by high-performance liquid chromatography (HPLC), and the pharmacokinetic parameters were calculated using DAS 2.1.1. Results The evodiamine inclusion complex showed a better water solubility (18.46 ± 0.36 μg/mL) and a higher cumulative release percentage [(76.8±4.9)%] than free evodiamine. The pharmacokinetic parameters of evodiamine inclusion complex and free evodiamine in rats were as follows: Cmax, 252.5±12.43 vs 161.3±3.45 μg/L; Tmax, 4.00±0 vs 4.07±0 h; MRT0-∞, 8.46± 0.91 vs 4.43±0.74 h; AUC0-t, 2266.40±28.64 vs 911.92±8.53 μg·L-1·h-1; AUC0-∞, 2359.76±31.58 vs 919.16±9.73 μg·L-1·h-1. The relative bioavailability of evodiamine inclusion complex was 256.73% . Conclusion Compared with free evodiamine, evodiamine inclusion complex has a higher bioavailability.