Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2487779 | Journal of Pharmaceutical Sciences | 2007 | 10 Pages |
Abstract
Previously, we clarified the species differences in Pâglycoprotein (Pâgp)âmediated drug transport activity using human MDR1, monkey MDR1, canine MDR1, rat MDR1a, rat MDR1b, mouse mdr1a, and mouse mdr1b transfected LLCâPK1 cell lines. However, the species differences in the inhibitory effects on Pâgpâmediated drug transport have not been clarified yet. The purpose of the present study was to evaluate the species differences in the inhibitory effects of typical Pâgp inhibitors, quinidine and verapamil, on Pâgpâmediated drug transport using MDR1 transfected cell lines. The transcellular transport of [3H]daunorubicin, [3H]digoxin, and [mebmtâβâ3H]cyclosporin A across monolayers of the MDR1 transfected cells were measured in the presence or absence of Pâgp inhibitors. On daunorubicin transport, the relative IC50 value (quinidine IC50/verapamil IC50) of human Pâgp was 5.25 and those from other species ranged from 0.89 to 10.70. The transport of digoxin and cyclosporin A also showed different relative IC50 values among human, monkey, canine, rat, and mouse Pâgps. The present study revealed that species differences in the inhibitory effects on Pâgpâmediated drug transport should not be disregarded among human, monkey, canine, rat, and mouse. This study will provide useful information for predicting drug interactions mediated by Pâgp.
Keywords
Related Topics
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Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Naoto Suzuyama, Miki Katoh, Toshiyuki Takeuchi, Sumie Yoshitomi, Tomoaki Higuchi, Satoru Asashi, Tsuyoshi Yokoi,