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논문 기본 정보

자료유형
학술저널
저자정보
Chae, Hye-Won (National Research Laboratory for Transproters Targeted Drug Design, College of Pharmacy, Seoul National University, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Se) Kim, In-Wha (National Research Laboratory for Transproters Targeted Drug Design, College of Pharmacy, Seoul National University, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seou) Jin, Hyo-Eon (National Research Laboratory for Transproters Targeted Drug Design, College of Pharmacy, Seoul National University, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seo) Kim, Dae-Duk (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University) Chung, Suk-Jae (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University) Shim, Chang-Koo (National Research Laboratory for Transproters Targeted Drug Design, College of Pharmacy, Seoul National University, Research Institute of Pharmaceutical Sciences, College o)
저널정보
대한약학회 Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea 제31권 제1호
발행연도
2008.1
수록면
103 - 110 (8page)

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The objective of this study was to examine the effect of ion-pair complexation with endogenous bile salts on the transport of a quarternary ammonium organic cationic (OC) drug, berberine, across the Caco-2 and LLC-PK1 cell monolayers. The basolateral-to-apical (BL-AP) transport of berberine in Caco-2 cells was temperature dependent and 10-fold higher than that of the apical-to-basolateral (AP-BL) transport. Similar results were observed for the transport of berberine across the LLC-PK1 cells. Moreover, the BL-AP transport in the Caco-2 cells was significantly reduced by the cis-presence of P-glycoprotein (P-gp) inhibitors such as cyclosporine A, verapamil, and digoxin. These results suggest that an efflux transporter, probably P-gp, is involved in the Caco-2 cell transport. The $K_m$ and $V_{max}$ values for the carrier-mediated transport were estimated to be 83.4 mM and 7640 pmole/h/$cm^2$, respectively. The apparent partition coefficient (APC) of berberine between n-octanol and a phosphate buffer (pH 7.4) was increased by the presence of an organic anion (OA), taurodeoxycholate (TDC, a bile salt), suggesting the formation of a lipophilic ion-pair complex between an OC (berberine) and an OA (TDC). Despite the ion-pair complexation, however, the BL-AP transport of berberine across the Caco-2 and LLC-PK1 cells was not altered by the cis-presence of bile salts or the rat bile juice. This is consistent with the reportedly unaltered secretory transport of a quarternary ammonium compound, tributylmethylammonium (TBuMA), across the Caco-2 cell monolayers in the cis-presence of bile salts or the rat bile juice, but not with our previous report in which the secretory transport of TBuMA across the LLC-PK1 cell was increased in the cis-presence of TDC. Therefore, the effect of ion-pair formation with the bile components or bile salts on the secretory transport of OCs appears to depend on the molecular properties of OCs (e.g., molecular weight, lipophilicity and affinity to relevant transporters) and the characteristics of cell strains (e.g., expression and contribution of responsible transporters to the transport).
#Berberine #Ion-pair effect #P-Glycoprotein #Caco-2 transport #Taurodeoxycholate

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