Jin Xin, Zhang Zhen-Hai, Sun E, Tan Xiao-Bin, Xia Hai-Jian, Liu Qi-Yuan, Jia Xiao-Bin
Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing 210028, China.
Yao Xue Xue Bao. 2013 Mar;48(3):411-6.
In this study, the biopharmaceutical properties of 20 (S)-protopanaxadiol (PPD) were studied. Firstly, the equilibrium solubility and apparent oil/water partition coefficient of PPD were used to predict the absorption in vivo. Meanwhile the membrane permeability and absorption window were studied by Caco-2 cell model and single-pass intestinal perfusion model. Furthermore, the bioavailability and metabolism were combined to study the absorption properties and metabolic properties in vivo. All of them were used to provide theoretical and practical foundation for designing PPD preparation. The results showed that PPD is poorly water-soluble, and the equilibrium solubility in water is only 35.24 mg x L(-1). The oil-water partition coefficient is 46.21 (logP = 1.66). By Caco-2 cell model, the results showed PPD uptake in general, and it also has efflux. By in situ intestinal perfusion model, the results showed that the absorption of PPD in the intestine is good, and the effective permeability coefficient were duodenum > jejunum > ileum > colon. The oral bioavailability of PPD was 29.39%. It was not well. Metabolic studies showed PPD in vivo presented a wide spread metabolism. So the main factors that restricted oral bioavailability of PPD were the poor solubility and first-pass effect.
在本研究中，对20（S）-原人参二醇（PPD）的生物药剂学性质进行了研究。首先，利用PPD的平衡溶解度和表观油/水分配系数来预测其体内吸收情况。同时，通过Caco-2细胞模型和单通道肠道灌注模型研究其膜通透性和吸收窗。此外，结合生物利用度和代谢情况来研究其体内吸收性质和代谢性质。所有这些研究均为PPD制剂的设计提供理论和实践基础。结果表明，PPD水溶性较差，在水中的平衡溶解度仅为35.24 mg·L⁻¹。油水分配系数为46.21（logP = 1.66）。通过Caco-2细胞模型研究发现，PPD总体上有摄取，但也存在外排。通过原位肠道灌注模型研究发现，PPD在肠道中的吸收良好，有效渗透系数为十二指肠＞空肠＞回肠＞结肠。PPD的口服生物利用度为29.39%，效果不佳。代谢研究表明，PPD在体内呈现广泛代谢。因此，限制PPD口服生物利用度的主要因素是溶解度差和首过效应。
