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.
Itagaki
Fumio
F
Department of Pharmaceutical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ten-nodai, Ibaraki, Japan. tfumioi-tuk@umin.ac.jp
Homma
Masato
M
Takara
Kohji
K
Ohnishi
Noriaki
N
Yokoyama
Teruyoshi
T
Sakaeda
Toshiyuki
T
Yagami
Tatsurou
T
Kobayashi
Hironao
H
Okamura
Noboru
N
Kohda
Yukinao
Y
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