薬物体内動態と MDR1 発現量に関連した<i>MDR1</i>遺伝子型

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書誌事項

タイトル別名
  • <i>MDR1</i> Genotypes Related to Pharmacokinetics and MDR1 Expression
  • 薬物体内動態とMDR1発現量に関連したMDR1遺伝子型
  • ヤクブツタイナイ ドウタイ ト MDR1 ハツゲンリョウ ニ カンレン シタ MDR1 イデンシガタ
  • MDR1 genotypes related to pharmacokinetics and MDR1 expression

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抄録

The multidrug-resistant transporter encoded by the MDR1 gene belongs to the ATP-binding cassette superfamily of membrane transporters. It is involved not only in the acquisition of multidrug-resistance phenotypes in cancer cells but also in normal tissues such as the brain, kidneys, liver, and intestines. This transporter has the potential to export unnecessary or toxic exogenous substances or metabolites, and in the intestine it is thought to play a role in limiting the oral absorption of a number of structurally unrelated drugs. In 2000, Hoffmeyer et al. performed a systemic screening for MDR1 polymorphisms and suggested that a single-nucleotide polymorphism (SNP) in exon 26 of the MDR1 gene (C3435T) was associated with a lower level of intestinal MDR1 expression, and thereby with lower plasma concentrations of digoxin after oral administration. At present, over 20 SNPs have been found in the MDR1 gene. Clinical studies on the effects of C3435T on MDR1 expression and function in the tissues, and consequently on the pharmacokinetics, have been performed worldwide. In this review, the latest reports concerning the relationship of MDR1 genotypes with pharmacokinetics and MDR1 expression are summarized. Our experimental results demonstrate the importance of genetic polymorphisms at positions 3435 and 2677 in the MDR1 gene on pharmacokinetics and intestinal MDR1 expression. In the future, haplotype analysis of the MDR1 gene and subsequent classification of subjects are needed for individualized pharmacotherapy based on MDR1 genotyping.<br>

収録刊行物

  • 薬学雑誌

    薬学雑誌 123 (9), 773-779, 2003-09-01

    公益社団法人 日本薬学会

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