Abstract
In the present study, we examined the roles of specific multidrug resistance proteins (MRPs) in the efflux transport of the phosphodiesterase type 5 inhibitors, vardenafil and sildenafil. Using MDCKII cells overexpressing MRP1, MRP2, and MRP3 (MDCKII-MRP1, -MRP2, and MRP3, respectively) as model systems, we measured the basal to apical and apical to basal transport of vardenafil and sildenafil at concentrations ranging from 1 to 100 μM. Vardenafil had a much greater basal to apical than apical to basal transport rate in MDCKII-MRP1, -MRP2, and MRP3 cells, suggesting that vardenafil is a substrate for MRP1, MRP2, and MRP3. In contrast, the basal to apical and apical to basal transport rate were similar to each other in each of the MRPs-overexpressing MDCKII cells, indicating that sildenafil was not pumped out via MRP1, MRP2, and MRP3. Vardenafil efflux from MDCKII-MRP1, MRP2, and MRP3 cells was concentration dependent and occurred with K m values of 48.2 ± 15.5, 12.8 ± 4.18, and 14.1 ± 7.4 μM, respectively. In conclusion, MRP1, MRP2, and MRP3 may influence the absorption, disposition, and cellular accumulation of vardenafil, but not sildenafil.
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