1997 Fiscal Year Final Research Report Summary
P-Glycoproten as a Molecular Target of Pharmacokinetic Studies for the Reversal of Multidrug Resistance
| Project/Area Number |
08672607
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
応用薬理学・医療系薬学
|
|---|
| Research Institution | KOBE UNIVERSITY |
|---|
Principal Investigator |
TANIGAWARA Yusuke Kobe University, University Hospital Faculty of Medicine, Associate Professor, 医学部・附属病院, 助教授 (30179832)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OKUMURA Katsuhiko Kobe Univesity, University Hospital Faculty of Medicine, Professor, 医学部・附属病院, 教授 (60025707)
|
|---|
| Project Period (FY) |
1996 – 1997
|
| Keywords | P-glycoprotein / Multidrug resistance / Transport / Pharmacokinetics / Anticancer agents / Chemosensitizer / chemosensitizer |
|---|
| Research Abstract |
Multidrug resistance (MDR) is a major obstacle in cancer chemotherapy. One of important mechanisms of MDR is P-glycoprotein (P-gp) which actively expels anticancer drugs out of the cells and decreased their intracellular concentration, resulting in the resistance aganinst multiple agents. Modulation of P-gp can reverse the MDR and many improve outcome of cancer chemotherapy.
1. SDZ PSC 833, a non-immunosuppressive cyclosporin derivative, was 5-to 10-fold more potent to reverse multidrug resistance compared to cyclosporin A.This is probably because PSC 833 is not transported by human P-gp and is more hydrophobic than Cs-A.
2. Transport activity in the MDR-transfected cells was well correlated with the expression level of P-gp protein.
3. Docetaxl, a new anticancer agent, was a substrate transported by P-gp.
4. Itraconazole inhibited the P-gp mediated transport of digoxin, suggesting a mechanism of clinically important digoxin-itraconazole interaction. Itraconazole also reversed sensitivity to vinblastine in the P-gp expressed cells.
5. Inhibitory effect of various Ca^<2+> antagonists on digoxin transport via P-gp was related to the molecular weight of Ca^<2+> antagonists.
|
Research Products
(16 results)
