DOI QR코드

DOI QR Code

In-Vitro 흡수특성 검색모델로서 Caco-2 및 MDCK 세포배양계의 특성 비교 평가

Comparison of Caco-2 and MDCK Cells As an In-Vitro ADME Screening Model

  • Go, Woon-Jung (BK21 Project team, College of Pharmacy, Chosun University) ;
  • Cheon, Eun-Pa (BK21 Project team, College of Pharmacy, Chosun University) ;
  • Han, Hyo-Kyung (BK21 Project team, College of Pharmacy, Chosun University)
  • 발행 : 2008.06.20

초록

The present study compared the feasibility of Caco-2 and MDCK cells as an efficient in-vitro model for the drug classification based on Biopharmaceutics Classification System (BCS) as well as an in-vitro model for drug interactions mediated by P-gp inhibition or P-gp induction. Thirteen model drugs were selected to cover BCS Class I{\sim}IV$ and their membrane permeability values were evaluated in both Caco-2 and MDCK cells. P-gp inhibition studies were conducted by using vinblastine and verapamil in MDCK cells. P-gp induction studies were also performed in MDCK cells using rifampin and the P-gp expression level was determined by western blot analysis. Compared to Caco-2 cells, MDCK cells required shorter period of time to culture cells before running the transport study. Both Caco-2 and MDCK cells exhibited the same rank order relationship between in-vitro permeability values and human permeability values of all tested model compounds, implying that those in-vitro models may be useful in the prediction of human permeability (rank order) of new chemical entities at the early drug discovery stage. However, in the case of BCS drug classification, Caco-2 cells appeared to be more suitable than MDCK cells. P-gp induction by rifampin was negligible in MDCK-cells while MDCK cells appeared to be feasible for P-gp inhibition studies. Taken all together, the present study suggests that Caco-2 cells might be more applicable to the BCS drug classification than MDCK-cells, although MDCK cells may provide some advantage in terms of capacity and speed in early ADME screening process.

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참고문헌

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