Chapter 5: Pharmacogenomics of Drug Transporters: Clinical Implications

研究成果: 著書/レポートタイプへの貢献

抄録

Drug transporters play an important role in the pharmacokinetic/pharmacodynamic consequences of many clinically used drugs. One possible reason for some of the inter-individual differences in drug pharmacokinetics/pharmacodynamics reported in humans is polymorphisms in transporter genes. Among the numerous variants identified to date, the functional significance of 174V>A in SLCO1B1 and 421C>A in ABCG2 has been recognized using in vitro expression and in vivo human studies. The maximum change observed in pharmacokinetic parameters [e.g., area under the plasma concentration-time curve (AUC)] due to these variants was approximately 300%. This value was less than for some drug transporter mediated drug-drug interactions; for example, the interaction between statins and cyclosporine via OATP1B1 has been associated with a maximum change of more than 1000% in the AUC; however, 300% is still potentially significant clinically. On the other hand, for P-glycoprotein (ABCB1), a well-known and important transporter that acts as an efflux barrier against chemical compounds in various human tissues, resulting in lower bioavailability and/or serum concentrations of substrate drugs with large inter-individual variability, the clinical significance of its gene polymorphisms has not yet been established. One possible reason for this is that the pharmacokinetic and pharmacodynamic properties of most substrate drugs for P-glycoprotein are regulated by multiple transporters and, thus, to accurately evaluate its genetic polymorphisms in humans, a specific probe P-glycoprotein substrate is essential. However, there is currently no specific substrate for P-glycoprotein. Since many clinically used drugs are substrates for multiple transporters, the concept that gene-gene interactions may be necessary for correctly evaluating genotype and phenotype relationships warrants future investigation. These issues may obscure the net in vivo functions of variants in humans. Therefore, numerous variants in other transporter genes, in addition to those already recognized in SLCO1B1 and ABCG2, need to be considered for new and existing drug treatments in the future as knowledge expands.

元の言語英語
ホスト出版物のタイトルPrivileged Scaffolds in Medicinal Chemistry
ホスト出版物のサブタイトルDesign, Synthesis, Evaluation
出版者Royal Society of Chemistry
ページ114-142
ページ数29
エディション55
DOI
出版物ステータス出版済み - 1 1 2016

出版物シリーズ

名前RSC Drug Discovery Series
番号55
2016-January
ISSN(印刷物)2041-3203
ISSN(電子版)2041-3211

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Pharmacogenetics
P-Glycoprotein
Pharmaceutical Preparations
Pharmacokinetics
Genes
Area Under Curve
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Genetic Polymorphisms
Drug Interactions
Individuality
Cyclosporine
Biological Availability
Genotype
Phenotype

All Science Journal Classification (ASJC) codes

  • Drug Discovery

これを引用

Ieiri, I. (2016). Chapter 5: Pharmacogenomics of Drug Transporters: Clinical Implications. : Privileged Scaffolds in Medicinal Chemistry: Design, Synthesis, Evaluation (55 版, pp. 114-142). (RSC Drug Discovery Series; 巻数 2016-January, 番号 55). Royal Society of Chemistry. https://doi.org/10.1039/9781782628705-00114

Chapter 5 : Pharmacogenomics of Drug Transporters: Clinical Implications. / Ieiri, Ichiro.

Privileged Scaffolds in Medicinal Chemistry: Design, Synthesis, Evaluation. 55. 編 Royal Society of Chemistry, 2016. p. 114-142 (RSC Drug Discovery Series; 巻 2016-January, 番号 55).

研究成果: 著書/レポートタイプへの貢献

Ieiri, I 2016, Chapter 5: Pharmacogenomics of Drug Transporters: Clinical Implications. : Privileged Scaffolds in Medicinal Chemistry: Design, Synthesis, Evaluation. 55 Edn, RSC Drug Discovery Series, 番号 55, 巻. 2016-January, Royal Society of Chemistry, pp. 114-142. https://doi.org/10.1039/9781782628705-00114
Ieiri I. Chapter 5: Pharmacogenomics of Drug Transporters: Clinical Implications. : Privileged Scaffolds in Medicinal Chemistry: Design, Synthesis, Evaluation. 55 版 Royal Society of Chemistry. 2016. p. 114-142. (RSC Drug Discovery Series; 55). https://doi.org/10.1039/9781782628705-00114
Ieiri, Ichiro. / Chapter 5 : Pharmacogenomics of Drug Transporters: Clinical Implications. Privileged Scaffolds in Medicinal Chemistry: Design, Synthesis, Evaluation. 55. 版 Royal Society of Chemistry, 2016. pp. 114-142 (RSC Drug Discovery Series; 55).
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