sildenafil-citrate and verlukast

We aimed to characterize the efflux transport properties of vardenafil and sildenafil, and to compare the kinetics of these compounds via efflux transporters such as P-gp, BCRP and MRP2.. We measured the basal-to-apical and apical-to-basal transport of vardenafil and sildenafil within the concentration range of 1-100 µm using MDCKII cells overexpressing P-gp, BCRP and MRP2, and Caco-2 cells.. Vardenafil had a much greater basal-to-apical than apical-to-basal transport rate in MDCKII cells overexpressing P-gp, BCRP and MRP2. Sildenafil showed P-gp- and BCRP-mediated efflux transport, but did not seem to be pumped out via MRP2 transporters. Consequently, the absorptive transport of vardenafil and sildenafil in Caco-2 cells increased linearly over the concentration range of 1-100 µm, whereas the secretory transport of these drugs was saturable and inhibited by the presence of specific inhibitors of P-gp and BCRP. MK571, a representative MRP2 inhibitor, inhibited the basal-to-apical transport of vardenafil, but not of sildenafil.. The involvement of P-gp, BCRP and MRP2 for vardenafil and the involvement of P-gp and BCRP for sildenafil in the secretory transport with linear absorptive transport may contribute to the limited intestinal absorption of these drugs.

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Biological Transport; Caco-2 Cells; Humans; Imidazoles; Intestinal Absorption; Leukotriene Antagonists; Multidrug Resistance-Associated Protein 2; Multidrug Resistance-Associated Proteins; Neoplasm Proteins; Phosphodiesterase 5 Inhibitors; Piperazines; Propionates; Purines; Quinolines; Sildenafil Citrate; Sulfones; Triazines; Vardenafil Dihydrochloride