title: Characterization of efflux transport of the PDE5 inhibitors, vardenafil and sildenafil.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: College of Pharmacy, Dankook University, Cheon-an             Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan             College of Pharmacy, Kyungpook National University, Daegu, Korea.
authors: Min-Koo
authors: MK
authors: Choi
authors: Im-Sook
authors: IS
authors: Song
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D001692:Biological Transport; D018938:Caco-2 Cells; D006801:Humans; D007093:Imidazoles / Q000378:metabolism / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D020024:Leukotriene Antagonists / Q000494:pharmacology; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D058986:Phosphodiesterase 5 Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics*; D010879:Piperazines / Q000378:metabolism / Q000493:pharmacokinetics*; D011422:Propionates / Q000494:pharmacology; D011687:Purines / Q000378:metabolism / Q000493:pharmacokinetics; D011804:Quinolines / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000378:metabolism / Q000493:pharmacokinetics*; D014227:Triazines / Q000378:metabolism / Q000493:pharmacokinetics; D000069058:Vardenafil Dihydrochloride
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D007093:Imidazoles; D020024:Leukotriene Antagonists; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011422:Propionates; D011687:Purines; D011804:Quinolines; D000068677:Sildenafil Citrate; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; C059141:verlukast