Order-made pharmacotherapy based on MDR1 genotyping

基于 MDR1 基因分型的定制药物治疗

• 批准号: 15590130
• 负责人: SAKAEDA Toshiyuki
• 金额: $ 2.24万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590130/
• 关键词: Drug transporters; MDR1; Gene; Genotyping; Pharmacogenomics; Pharmacogenetics; Digixin; Cyclosporine; MDRI; ファーマコジュネティクス; ジゴキシン

This research was conducted to examine the possibility of MDR1 genotyping to establish the order-made pharmacotherapy. MDR1 is a 170kDa membrane protein, which is expressed in the normal tissues including intestine, brain and kidneys, and acts as efflux transporter of exogenous toxic substances out of the cells, and therefore regulates the pharmacokinetics of a number of drugs. Herein, we elucidated that 1)the serum concentration-time profiles of digoxin after single oral administration was defined by MDR1 C3435T, located in exon 26; 2)the expression of MDR1 mRNA in the intestinal mucosa was defined also by MDR1 C3435T. Briefly, the digoxin concentrations were higher in the subjects with C-allele, and the expression of MDR1 mRNA was lower in the subjects. Based on these investigations with healthy subjects, we also found that 3)cyclosporine pharmacokinetics was defined by MDR1 C3435T. These data were published as 6 original articles and 4 review articles.

本研究旨在探讨MDR 1基因分型建立序贯药物治疗的可能性。MDR 1是一种分子量为170 kDa的膜蛋白，主要表达于肠、脑、肾等正常组织中，作为外源性毒性物质的外排转运蛋白，调节多种药物的药代动力学。在此，我们阐明了1）地高辛单次口服给药后的血清浓度-时间曲线由位于外显子26的MDR 1 C3435 T定义; 2）肠粘膜中MDR 1 mRNA的表达也由MDR 1 C3435 T定义。简而言之，地高辛浓度在具有C等位基因的受试者中较高，并且MDR 1 mRNA表达在受试者中较低。基于对健康受试者的这些研究，我们还发现3）环孢素药代动力学由MDR 1 C3435 T定义。这些数据发表为6篇原创文章和4篇综述文章。

项目成果

Significant genetic linkage of MDR1 polymorphisms at,

MDR1 多态性的显着遗传连锁，

• 发表时间: 2002
• 期刊: Pharm.Res. 19(10)
• 作者: M.Horinouchi;et al.
• 通讯作者: et al.

Pharmacogenetics of drug transporters and its impact on the pharmacotherapy.

• DOI: 10.2174/1568026043387692
• 发表时间: 2004-08
• 期刊: Current topics in medicinal chemistry
• 影响因子: 3.4
• 作者: T. Sakaeda;Tsutomu Nakamura;K. Okumura

Effects of polymorphisms of MDR1, MRP1, and MRP2 genes on their mRNA expression levels in duodenal enterocytes of healthy Japanese subjects

• DOI: 10.1248/bpb.25.1356
• 发表时间: 2002-10-01
• 期刊: BIOLOGICAL & PHARMACEUTICAL BULLETIN
• 影响因子: 2
• 作者: Moriya, Y;Nakamura, T;Okumura, K
• 通讯作者: Okumura, K

Pharmacogenetics of MDR and MRP subfamilies

MDR 和 MRP 亚家族的药物遗传学

• 发表时间: 2004
• 期刊: Personalized Med.(PMID: not defined yet) 1(1)
• 作者: N.Okamura;T.Sakaeda;K.Okumura
• 通讯作者: K.Okumura

Effects of polymorphisms of MDR1, MRP1, and MRP2 genes,

MDR1、MRP1 和 MRP2 基因多态性的影响，

• 发表时间: 2002
• 期刊: Biol.Pharm.Bull. 25(10)
• 作者: Y.Moriya;et al.
• 通讯作者: et al.