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Species Differences of Inhibitory Effects on P‐glycoprotein‐mediateD Drug Transport by Naoto Suzuyama; Miki Katoh; Toshiyuki Takeuchi; Sumie Yoshitomi; Tomoaki Higuchi; Satoru Asashi; Tsuyoshi Yokoi is a Chemistry article available to read on EtoBox.

What is Species Differences of Inhibitory Effects on P‐glycoprotein‐mediateD Drug Transport about?

Previously, we clarified the species differences in P-glycoprotein (P-gp)mediated drug transport activity using human MDR1, monkey MDR1, canine MDR1, rat MDR1a, rat MDR1b, mouse mdr1a, and mouse mdr1b transfected LLC-PK 1 cell lines. However, the species differences in the inhibitory effects on P-gp-mediated 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 P-gp inhibitors, quinidine and verapamil, on P-gp-mediated drug transport using MDR1 transfected cell lines. The transcellular transport of [ 3 H]daunorubicin, [ 3 H]digoxin, and [mebmt-b-3 H]cyclosporin A across monolayers of the MDR1 transfected cells were measured in the presence or absence of P-gp inhibitors. On daunorubicin transport, the relative IC 50 value (quinidine IC 50 /verapamil IC 50 ) of human P-gp 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 IC 50 values among human, monkey, canine, rat, and mouse P-gps. The present study revealed that species differences in the inhibitory effects on P-gp-mediated drug transport should

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Author

Naoto Suzuyama; Miki Katoh; Toshiyuki Takeuchi; Sumie Yoshitomi; Tomoaki Higuchi; Satoru Asashi; Tsuyoshi Yokoi

Publisher

John Wiley and Sons; Elsevier ; Elsevier Inc.; Elsevier BV (ISSN 0022-3549)

Published

2007

Language

EN

Field

Chemistry (Physical Sciences)