Interactions between P-glycoprotein and drugs used in the supportive care of acute myeloid leukemia patients

Multidrug resistance due to overexpression of P-glycoprotein (Pgp) leads to reduced intracellular drug accumulation and makes the cells resistant to c hemotherapy. In this study we focused on how drugs used in the supportive c are of acute myeloid leukemia (AML) patients interfere with Pgp., The effec t on intracellular accumulation of the fluorescent dye Rhodamine 123 (Rh 12 3) was studied in the human promyelocytic leukemia cell line HL-60 and two anthracycline resistant, Pgp expressing, sublines. Each drug was used at tw o different concentrations: plasma peak concentration and half the plasma p eak concentration. Drugs which increased the Rh 123 uptake by >10% were inc luded in the second part of the study where the cytotoxic effect was tested in combination with daunorubicin. In the Rhodamine assay none of the teste d drugs had any significant effect on the Rh 123 efflux in the resistant ce ll lines. Amphotericin B, cefuroxime, erythromycin and dixyrazin had minor effects on Rh 123 uptake but showed a significant additive effect to the to xicity of daunorubicin suggesting other mechanisms of action than reversal of Pgp. In conclusion this in vitro model where Rh 123 uptake was studied i n an anthracycline resistant leukemia cell line could not demonstrate any s ignificant interactions with Pgp for the tested drugs.