| Project/Area Number |
16590119
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Josai University |
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Principal Investigator |
UEDA Hideo Josai University, Faculty of Pharmaceutical Sciences, Research Associate, 薬学部, 助手 (50326998)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Daisuke Josai University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (60306248)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | human / mammary / culture / lactation |
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| Research Abstract |
Physician must take account of infant drug exposure from breast milk in pharmacotherapy for lactating mother. Our goal is to define a safer drug for suckling infant and lactating mother. Development of a human mammary epithelial cell (HMEC) culture model has been attempted to evaluate a drug transfer into milk. Trypsin-resistant HMECs were seeded on 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. Using RT-PCR analysis and Western blotting analysis, we showed the expression of β-casein, an index of differentiation, in 3-t-HMEC. It suggested that 3-t-HMEC monolayer functionally differentiated as well as mammary epithelial cell during lactation In permeation study, 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), and the saturation in TEA uptake transport was observed (Km=3.904μM, Vmax=2.03 pmol/mg protein/min), suggesting the existence of organic cation transporters. In fact, expression of mRNAs of human organic cation transporter (hOCT) 1 and 3 were detected in the 3-t-HMEC monolayer by RT-PCR analysis.
These results suggested that trypsin-resistant HMEC monolayers was useful for evaluation of carrier-mediated drug transport during the lactating stage. In future integration of the carrier-mediated processes with the prediction models in addition to the passive diffusion process based on the physicochemical properties of drugs enables us to accurately predict drug transfer into human milk. Development of such integrated prediction models is now required.
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