Functional significance of genetic polymorphisms in P-glycoprotein (MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2)

研究成果: ジャーナルへの寄稿記事

106 引用 (Scopus)

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Summary: Recent pharmacogenomic/pharmacogenetic (PGx) studies have disclosed important roles for drug transporters in the human body. Changes in the functions of drug transporters due to drug/food interactions or genetic polymorphisms, for example, are associated with large changes in pharmacokinetic (PK) profiles of substrate drugs, leading to changes in drug response and side effects. This information is extremely useful not only for drug development but also for individualized treatment. Among drug transporters, the ATP-binding cassette (ABC) transporters are expressed in most tissues in humans, and play protective roles; reducing drug absorption from the gastrointestinal tract, enhancing drug elimination into bile and urine, and impeding the entry of drugs into the central nervous system and placenta. In addition to PK/pharmacodynamic (PD) issues, ABC transporters are reported as etiologic and prognostic factors (or biomarkers) for genetic disorders. Although a consensus has not yet been reached, clinical studies have demonstrated that the PGx of ABC transporters influences the overall outcome of pharmacotherapy and contributes to the pathogenesis and progression of certain disorders. This review explains the impact of PGx in ABC transporters in terms of PK/PD, focusing on P-glycoprotein and breast cancer resistance protein (BCRP).

元の言語英語
ページ(範囲)85-105
ページ数21
ジャーナルDrug metabolism and pharmacokinetics
27
発行部数1
DOI
出版物ステータス出版済み - 1 1 2012

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P-Glycoprotein
Genetic Polymorphisms
Breast Neoplasms
ATP-Binding Cassette Transporters
Pharmaceutical Preparations
Proteins
Pharmacokinetics
Food-Drug Interactions
Central Nervous System Agents
Inborn Genetic Diseases
Pharmacogenetics
ATP Binding Cassette Transporter, Sub-Family G, Member 2
Drug-Related Side Effects and Adverse Reactions
Human Body
Bile
Placenta
Gastrointestinal Tract
Biomarkers
Urine
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

これを引用

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abstract = "Summary: Recent pharmacogenomic/pharmacogenetic (PGx) studies have disclosed important roles for drug transporters in the human body. Changes in the functions of drug transporters due to drug/food interactions or genetic polymorphisms, for example, are associated with large changes in pharmacokinetic (PK) profiles of substrate drugs, leading to changes in drug response and side effects. This information is extremely useful not only for drug development but also for individualized treatment. Among drug transporters, the ATP-binding cassette (ABC) transporters are expressed in most tissues in humans, and play protective roles; reducing drug absorption from the gastrointestinal tract, enhancing drug elimination into bile and urine, and impeding the entry of drugs into the central nervous system and placenta. In addition to PK/pharmacodynamic (PD) issues, ABC transporters are reported as etiologic and prognostic factors (or biomarkers) for genetic disorders. Although a consensus has not yet been reached, clinical studies have demonstrated that the PGx of ABC transporters influences the overall outcome of pharmacotherapy and contributes to the pathogenesis and progression of certain disorders. This review explains the impact of PGx in ABC transporters in terms of PK/PD, focusing on P-glycoprotein and breast cancer resistance protein (BCRP).",
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N2 - Summary: Recent pharmacogenomic/pharmacogenetic (PGx) studies have disclosed important roles for drug transporters in the human body. Changes in the functions of drug transporters due to drug/food interactions or genetic polymorphisms, for example, are associated with large changes in pharmacokinetic (PK) profiles of substrate drugs, leading to changes in drug response and side effects. This information is extremely useful not only for drug development but also for individualized treatment. Among drug transporters, the ATP-binding cassette (ABC) transporters are expressed in most tissues in humans, and play protective roles; reducing drug absorption from the gastrointestinal tract, enhancing drug elimination into bile and urine, and impeding the entry of drugs into the central nervous system and placenta. In addition to PK/pharmacodynamic (PD) issues, ABC transporters are reported as etiologic and prognostic factors (or biomarkers) for genetic disorders. Although a consensus has not yet been reached, clinical studies have demonstrated that the PGx of ABC transporters influences the overall outcome of pharmacotherapy and contributes to the pathogenesis and progression of certain disorders. This review explains the impact of PGx in ABC transporters in terms of PK/PD, focusing on P-glycoprotein and breast cancer resistance protein (BCRP).

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