DDS_EstPermeability__09 - Permeability Screening in Early...

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Permeability Screening in Early Drug Development
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Measuring Permeability In vivo/in situ models human dog, pig, other rat (in situ) In vitro models Excised tissue Cell culture Synthetic PAMPA (parallel artificial membrane) artificial membranes
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In Situ Perfusion
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In Vitro Permeability Measurement Ussing/Diffusion Chambers
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Comparison of Methods
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Diffusion Chambers
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Cell Culture Systems Used to Measure Permeability
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Caco-2 Cell Cultures Derived from human colon adenocarcinoma immortalized (generally use passage 20-40; up to 100) Heterogeneous cell population Careful of cell selection/drift Form tight junctions Properties similar to colon vs. small intestine Spontaneously differentiate/polarize*
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Transporter expression is time/passage dependent and can vary depending on culturing conditions Moderate P-gp expression (lower than jejunum) Limited BCRP expression (lower than jejunum) MRP 1-6 expressed Enzyme expression
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This note was uploaded on 01/28/2010 for the course CHEM 130 taught by Professor Kia during the Spring '09 term at Abraham Baldwin Agricultural College.

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DDS_EstPermeability__09 - Permeability Screening in Early...

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