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        Development of a Human Mammary Epithelial Cell Culture Model for Evaluation of Drug Transfer into Milk

        Kimura Soichiro,Morimoto Keiko,Okamoto Hiroshi,Ueda Hideo,Kobayashi Daisuke,Kobayashi Jun,Morimoto Yasunori The Pharmaceutical Society of Korea 2006 Archives of Pharmacal Research Vol.29 No.5

        In the present study, a human mammary epithelial cell (HMEC) culture model was developed to evaluate the potential involvement of carrier-mediated transport systems in drug transfer into milk. Trypsin-resistant HMECs were seeded on $Matrigel^{circledR}-coated$ filters to develop monolayers of functionally differentiated HMEC. Expression of the specific function of HMEC monolayers was dependent of the number of trypsin treatments. Among the monolayers with different numbers of treatment (treated 1 to 3 times), the monolayer treated 3 times (3-t-HMEC monolayer) showed the highest maximal transepithelial resistance and expression of $\beta-casein$ mRNA as an index of differentiation. Transport of tetraethylammonium (TEA) across the 3-t-HMEC monolayer in the basolateral-to-apical direction was significantly higher than that in the apical-to-basolateral direction (p<0.05), whereas such directionality was not observed for p-aminohippurate, suggesting the existence of organic cation transporters, but not organic anion transporters. In fact, expression of mRNAs of human organic cation transporter (OCT) 1 and 3 were detected in the 3-t-HMEC monolayer. These results indicate that the 3-t-HMEC monolayer is potentially useful for the evaluation of carrier-mediated secretion of drugs including organic cations into human milk.

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        Development of a Human Mammary Epithelial Cell Culture Model for Evaluation of Drug Transfer into Milk

        Soichiro Kimura,Keiko Morimoto,Hiroshi Okamoto,Hideo Ueda,Daisuke Kobayashi,Jun Kobayashi,Yasunori Morimoto 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.5

        In the present study, a human mammary epithelial cell (HMEC) culture model was developed to evaluate the potential involvement of carrier-mediated transport systems in drug transfer into milk. Trypsin-resistant HMECs were seeded on Matrigel-coated filters to develop monolayers of functionally differentiated HMEC. Expression of the specific function of HMEC monolayers was dependent of the number of trypsin treatments. Among the monolayers with different numbers of treatment (treated 1 to 3 times), the monolayer treated 3 times (3-t-HMEC monolayer) showed the highest maximal transepithelial resistance and expression of β-casein mRNA as an index of differentiation. Transport of tetraethylammonium (TEA) across the 3-t-HMEC monolayer in the basolateral-to-apical direction was significantly higher than that in the apicalto- basolateral direction (p < 0.05), whereas such directionality was not observed for p-aminohippurate, suggesting the existence of organic cation transporters, but not organic anion transporters. In fact, expression of mRNAs of human organic cation transporter (OCT) 1 and 3 were detected in the 3-t-HMEC monolayer. These results indicate that the 3-t-HMEC monolayer is potentially useful for the evaluation of carrier-mediated secretion of drugs including organic cations into human milk.

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        Effect of Several Adsorbents on The Gastrointestinal Absorption of Paraquat

        Machijima, Hiraku,Nakamura, Hiroyuki,Hatanaka, Tomomi,Sugibayashi, Kenji,Morimoto, Yasunori The Pharmaceutical Society of Korea 1994 Archives of Pharmacal Research Vol.17 No.5

        The effect of several adsorbents on paraquat poisohing was investigated (1) by measuring the saturatd amount of the poison adhered on the adsorbents in vitro and (2) by assaying the blood level of paraquat in the rat in in situ intestinal absorption experiments. Activated charcoal powder, natural aluminum silifonate) were used as adorbents. The steady-state blood level of paraquat in its absorption experiment with the cationic exchange resins was markedly lower than those without the resins or with other adsorbents. A good relationship was achieved between the calculated AUC or adsorptioin rate (in situ) and the saturated adsorption amount (in vitro). The rank order of the effect was sodium polystyene sulfonate > calcium polystyene sulfonate>natural aluminum silicate>activated charcoal powder. The effect of sodium polystyrene sulfonate after intestinal washing with physiological saline ws also measured, and a synergistic effect (marked decrease in blood paraquat level0 was found as compared with the intestinal washing alone. The simultaneous use of G.I. weshing and powerful adsorbent was scientifically proven to be most benefical.

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