Characterization of efflux transport of the PDE5 inhibitors, vardenafil and sildenafil.
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Choi MK, Song IS
Characterization of efflux transport of the PDE5 inhibitors, vardenafil and sildenafil.
J Pharm Pharmacol. 2012 Aug;64(8):1074-83. doi: 10.1111/j.2042-7158.2012.01498.x. Epub 2012 Mar 16.
- PubMed ID
- 22775210 [ View in PubMed]
- Abstract
OBJECTIVES: 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 microm using MDCKII cells overexpressing P-gp, BCRP and MRP2, and Caco-2 cells. KEY FINDINGS: 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 microm, 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. CONCLUSION: 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.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Sildenafil P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails Vardenafil P-glycoprotein 1 Protein Humans UnknownSubstrateInhibitorDetails