The combination of intravenous Proemend ® containing fosaprepitant meglumine, a prodrug for fosaprepitant (FAP), and Tween 80 and chemotherapy with anthracyclines, such as epirubicin (EPI), can cause infusion-site adverse events in clinical practice. In immortalized human umbilical vein endothelial (HUEhT-1) cells, the cytotoxic effects of FAP, EPI, diluted Proemend with culture medium and Tween 80 alone, and a combination of FAP and EPI, were evaluated using the WST-1 cell viability assay. FAP, EPI and diluted Proemend exhibited cytotoxicity in a concentration-dependent manner and marked synergic cytotoxicity was observed between FAP and EPI. The washing of the cell surface following incubation with diluted Proemend containing FAP and Tween-80 eliminated the synergic cytotoxicity of EPI applied thereafter. These results indicated that washing of the infusion-site vascular tissue following intravenous Proemend administration via intravenous tube flushing with an efficient amount of saline may reduce the infusion-site adverse events, which are caused by the combined use of FAP and EPI.
The combination of intravenous fosaprepitant dimeglumine (FAP, Proemend® I.V. Infusion), an antiemetic drug, and chemotherapy with anthracyclines such as epirubicin (EPI) can cause infusionsite adverse events. Avoiding method of infusion-site adverse events was studied in immortalized human umbilical vein endothelial (HUEhT-1) cells and rats. Cytotoxicity of FAP, EPI, diluted Proemend®, Tween 80 and a combination of FAP and EPI, and the effect of cell-surface washing after application of diluted Proemend® on cytotoxicity were studied in HUEhT-1 cells. In rats, the effect of infusion-site washing after FAP infusion was evaluated by measuring the intravascular accumulation of EPI in the combined use of FAP followed by EPI. FAP, EPI, and diluted Proemend® exhibited cytotoxicity concentration-dependently and marked synergistic cytotoxicity was observed between FAP and EPI. In HUEhT-1 cells, the washing of the cell surface after the application of FAP reduced the synergistic cytotoxicity significantly. In rats, the washing of the infusion site with saline after FAP infusion greatly decreased the intravascular accumulation of EPI infused thereafter. In conclusion, the washing of the infusion site by IV tube flushing after FAP infusion avoids the infusion-site adverse events due to the decrease in the vascular accumulation of EPI administered thereafter.
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