伐司扑达

Valspodar (PSC 833) has no cytotoxicity effects at up to the concentration of 0.75 μg/mL. Valspodar (0.25, 0.5 and 0.75 μg/mL) and DOX-L are added to the DOX resistant cells, and cell kill efficacy of MDR cell type increases significantly when valspodar is administered alongside DOX-L. Valspodar (0.5 and 0.75 μg/mL), in combination with all concentrations of DOX, are most toxic and kill more than 70% of the resistant cells. Pretreatment with PSC833 decreases the IC ₅₀ value of NSC 279836 in MDA-MB-435mdr cells to 0.4±0.02 μM in MDR cells and almost completely reverses the resistance of MDR cells to NSC 279836.

valspodar (10 mg/kg, o.p.) exhibits minimal blood-cell partitioning as reflected in its low mean blood-to-plasma ratio of approximately 0.52. Valspodar displays properties of slow clearance and a large volume of distribution. Valspodar shows properties of low hepatic extraction and wide distribution, similar to that of its structural analogue CsA. Preadministration of PSC833 to mice increases NSC 279836 fluorescent intensity in MDR tumor to 94% of that in the wild-type tumors.