Effect of rabeprazole on MDR1-mediated transport of Rhodamine 123 in Caco-2 and Hvr100-6 cells.
The aim of our study was to investigate the effects of rabeprazole, a proton pump inhibitor, on MDR1 expressed on human colon carcinoma cell line, Caco-2, and MDR1-overexpressing human cervical carcinoma cell line, HeLa cells selected by exposure to 100 nM vinblastine (Hvr100-6 cells). Inhibitory effects of rabeprazole on MDR1-mediated transport of Rhodamine123 were examined in these cells. A thousand micro molar rabeprazole increased Rhodamine 123 uptakes in Caco-2 and Hvr100-6 cells by 68% and 185%, respectively. No significant effects of rabeprazole were observed at the concentration of 1-100 microM. Since rabeprazole did not show any effects on Rhodamine 123 transport via MDR1 at the plasma levels (approximately 1 microM), it was considered that the drug interaction with MDR1 substrates would be minimal even though the interaction occurred in the patients with rabeprazole treatment.
Department of Pharmaceutical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ten-nodai, Ibaraki, Japan. tfumioi-tuk@umin.ac.jp
Fumio
F
Itagaki
Masato
M
Homma
Kohji
K
Takara
Noriaki
N
Ohnishi
Teruyoshi
T
Yokoyama
Toshiyuki
T
Sakaeda
Tatsurou
T
Yagami
Hironao
H
Kobayashi
Noboru
N
Okamura
Yukinao
Y
Kohda
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D001562:Benzimidazoles / Q000494:pharmacology*; D001692:Biological Transport; D018938:Caco-2 Cells; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000494:pharmacology*; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D020112:Rhodamine 123 / Q000493:pharmacokinetics*; D014747:Vinblastine / Q000494:pharmacology
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D054328:Proton Pump Inhibitors; D020112:Rhodamine 123; D064750:Rabeprazole; D014747:Vinblastine; D009853:Omeprazole