Application of an in vitro DDASS to evaluate oral absorption of two chemicals simultaneously: establishment of a level A in vitro-in vivo correlation

作者：Hou Jipeng; He Xin^*; Xu Xuefang; Shi Xiaoyan; Xu Yanyan; Liu Changxiao

来源：Drug Development and Industrial Pharmacy, 2012, 38(11): 1305-1312.

DOI：10.3109/03639045.2011.650642

• Drug dissolution/absorption simulating system (DDASS)
• in vitro/in vivo correlations (IVIVC)
• ferulic acid (FA)
• tetrahydropalmatine (THP)
• pharmacokinetics
• biopharmaceutics classification system (BCS)

The aim of this study was to evaluate the oral absorption of two chemicals simultaneously using a drug dissolution/absorption simulating system (DDASS), and to establish a correlation between DDASS and in vivo absorption to clarify the prediction of this in vitro model. Ferulic acid (FA) and tetrahydropalmatine (THP), the components of Angelicae Sinensis Radix and Corydalis Yanhusuo Rhizoma, respectively, were chosen as model compounds. Three groups including FA, THP, and FA and THP together (FA + THP) were studied in DDASS. The corresponding in vivo pharmacokinetics study was performed in rats. Then the correlation was analysed between DDASS permeation in vitro and rat absorption data in vivo. A strong level A correlation (r > 0.84) was obtained after a correlation coefficient test (p < 0.05 or 0.01). Moreover, when FA and THP were used together in DDASS, the cumulative permeation of FA increased by 38.5%, while THP permeation decreased by 25.8%. In rats, the area under the concentration-time curve from time to infinity for FA increased 2.6-fold, while THP decreased 19.6%. The changes in rat intestinal permeation modeled by the DDASS were consistent with the absorption changes in rats. We conclude that DDASS is a valid in vitro model to evaluate oral absorption of two drug components simultaneously and reflect the in vivo characteristics of drug absorption accurately.

• 出版日期2012-11
• 单位天津中医药大学; 天津药物研究院有限公司