Human Drug Transporter Gene-expressing Cells are Useful Alternatives to Predict Pharmacokinetics in Man
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概要
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The liver, kidney, intestine and brain possess a wide variety of drug transporters which are very important attributes in drug disposition, safety and efficacy. Consequently, it is now well recognized that obtaining information regarding drug transporters is fundamental during novel drug development. Recent molecular cloning endeavors have identified several families (i.e. SLC22 family) of multi-specific drug transporters including organic anion and organic cation transporters (OATs/OCTs). However, genome-based drug discovery has resulted in its own set of difficulties (i.e. species differences between human and other animals) and will require animals to examine the disposition of drugs in vivo. Herein, we present an example regarding organic solute transport properties and species differences; we summarize data regarding substrate specificities among OATs/OCTs obtained from human drug transporter gene-expressing cells. The presented substrate specificity data suggest that contribution to pharmacokinetics appears to be different for each drug in vivo. Therefore, the introduction of these transporter gene-expressing cells in early drug development will lead to contributions not only in refinement, but will assist in the reduction and replacement (i.e. the three R's concept: Reduction, Replacement and Refinement) for alternatives to animal usage.
- 日本動物実験代替法学会の論文
日本動物実験代替法学会 | 論文
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