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Transport of a new erectogenic udenafil in caco-2 cells

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Abstract

P-glycoprotein, an ATP-dependent efflux pump, is a membrane transporter that influences the absorption and excretion of drugs. There is a striking overlap between the substrates for CYP3A4 and P-glycoprotein. This study was designed to assess whether udenafil, a substrate of CYP3A4, is also a P-glycoprotein substrate. Udenafil stimulated P-glycoprotein ATPase activity, a putative measure of P-glycoprotein affinity, although with lower affinity than a proven substrate, verapamil. Bidirectional transport studies of udenafil using Caco-2 cell monolayers showed that its efflux (15.9-22.8 x 106 cm/s) was significantly higher than its influx (3.7-9.1 × 106 m/s). P-glycoprotein inhibitors such as cyclosporine, tariquidar and verapamil significantly increased the influx of udenafil and decreased the efflux of udenafil. These results indicate that udenafil is a substrate for P-glycoprotein. The low bioavailability, variable absorption and drug-drug interactions of udenafil may be related to the variability of CYP3A4 and P-glycoprotein expression and to possible CYP3A4 and P-glycoprotein interactions.

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Correspondence to Hye Young Ji or Hyun Joo Shim or Moohi Yoo or Eun-Seok Park or Hye Suk Lee.

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Ji, H.Y., Shim, H.J., Yoo, M. et al. Transport of a new erectogenic udenafil in caco-2 cells. Arch Pharm Res 30, 1168 (2007). https://doi.org/10.1007/BF02980254

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Key words

  • Udenafil
  • P-glycoprotein
  • Caco-2
  • Transport