Zentrix – Volume 2
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ZeRiX Krusader.Artemisinin and artesunate influence P-glycoprotein function in Caco-2 cells.
The influence of artemisinin and its active metabolite, artesunate, on transport of the substrates verapamil and digoxin was studied. In order to investigate the effect of these drugs on P-glycoprotein activity, Caco-2 cells were used as an in vitro model of intestinal transport. For this purpose Caco-2 cells were seeded in both monolayers and in insert compartments. At confluence, cells were treated with verapamil (10 microM), digoxin (10 microM), artemisinin (30 microM), and artesunate (30 microM) over 24 h. In addition, transport of verapamil and digoxin in Caco-2 cells was studied in cells treated with or without the P-glycoprotein inhibitor PSC833 (100 microM) and cyclosporine A (100 microM) for 2 h. The drug-free monolayers from Caco-2 cells grown in the insert were used as a control, and the transport in these cells was defined as the control transport. Artemisinin and artesunate as well as PSC833 inhibited (20-50%) the basal transport of verapamil and digoxin into the cells as compared with the control. Cytotoxicity was observed when the drugs were added for 24 h, although no effect was seen at lower concentrations. Verapamil transport increased, whereas digoxin transport decreased after cyclosporine A treatment. Digoxin transport was sensitive to P-glycoprotein inhibition. Artemisinin and artes
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