Effect of p-glycoprotein inhibitor combinations on drug efflux from rat brain microvessel endothelial cells.

In an effort to develop a clinically useful approach to inhibit the drug efflux across the blood brain barrier (BBB) mediated by P-glycoprotein (P-gp), the combined inhibitory effect of four P-gp inhibitors: cyclosporin A (CsA), verapamil (Ver), tetrandrine (Tet) and doxorubicin (Dox), was evaluated by determining the intracellular concentration of rhodamine 123 in in vitro cultured rat brain microvessel endothelial cells (BMEC). The results showed that CsA combined with Ver or Tet synergistically inhibited P-gp mediated efflux of Rh123 from rat BMEC, suggesting that the combined application of P-gp inhibitors would possibly be a useful approach to increase drug concentration in brain tissues, enhance the therapeutic effect and reduce the toxicity of drugs.