Project/Area Number |
15590130
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Medical pharmacy
|
Research Institution | Kobe University |
Principal Investigator |
SAKAEDA Toshiyuki Kobe University, Hospital, Associate Professor, 医学部附属病院, 助教授 (00304098)
|
Co-Investigator(Kenkyū-buntansha) |
OKUMURA Katsuhiko Kobe University, Hospital, Professor, 医学部附属病院, 教授 (60025707)
AOYAMA Nobuo Kobe University, Hospital, Associate Professor, 医学部附属病院, 助教授 (30243299)
|
Project Period (FY) |
2003 – 2004
|
Project Status |
Completed (Fiscal Year 2004)
|
Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
Keywords | 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 |
Research Abstract |
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.
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