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Effect of CJX2, an amlodipine derivative, combined with verapamil on P‐glycoprotein efflux function in vitro
Author(s) -
Ji BianSheng,
Li Ming,
He Ling
Publication year - 2009
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20321
Subject(s) - verapamil , p glycoprotein , efflux , pharmacology , in vitro , chemistry , k562 cells , microvessel , doxorubicin , biological activity , biochemistry , medicine , chemotherapy , calcium , angiogenesis , multiple drug resistance , organic chemistry , antibiotics
In an effort to inhibit P‐glycoprotein (P‐gp) efflux function with greater activity and less side effects, the combined effect of CJX2 and verapamil (Ver) was evaluated isobolographically in fixed ratio combinations of 1:1, 1:2, 1:4, 1:8, and 1:10 in doxorubicin‐resistant human myelogenous leukemia (K562/DOX ) cells and rat brain microvessel endothelial cells (RBMEC). The results displayed that mixtures of both drugs at the fixed ratios of 1:1, 1:2, 1:4, 1:8, and 1:10 exerted synergistic interactions, indicating that when the two blockers that bind P‐gp on separate membrane sites were combined, each contributes to the overall interaction with P‐gp, leading to the greater effect than that seen by either agent alone. Drug Dev Res, 2009. © 2009 Wiley‐Liss, Inc.