The disposition of three phosphodiesterase type 5 inhibitors, vardenafil, sildenafil, and udenafil, is differently influenced by the CYP3A5 genotype

Pharmacogenet Genomics. 2011 Dec;21(12):820-8. doi: 10.1097/FPC.0b013e32834b79e6.


Objectives: This study was conducted to compare the effect of CYP3A5*3 genotype on the disposition of three phosphodiesterase type 5 inhibitors (PDE5Is), vardenafil, sildenafil, and udenafil, because our previous in-vitro microsomal incubation study showed that the relative contribution of CYP3A5 enzyme to their metabolism was different among these PDE5Is.

Methods: An open-label three-way crossover study was performed with a single oral dose of PDE5Is (20 mg vardenafil, 100 mg sildenafil, or 200 mg udenafil) in 21 healthy men carrying CYP3A5*1/*1, *1/*3, or *3/*3. After each dose, plasma concentrations of the parents and their major metabolites were measured up to 24 or 48 h.

Results: The AUC(∞) and C(max) of vardenafil were 2.9-fold and 3.1-fold higher in CYP3A5*3/*3 carriers than in individuals with CYP3A5*1/*1 (P=0.003 and 0.002, respectively). The AUC(∞) and C(max) of sildenafil were 1.5-fold and 1.7-fold higher in CYP3A5*3/*3 carriers compared with individuals with CYP3A5*1/*1, but the statistical difference of both parameters among genotype groups was not observed. The disposition of udenafil differed little among groups in relation to the CYP3A5*3 allelic variant.

Conclusion: These results suggest that the disposition of these PDE5Is are differently influenced by the CYP3A5*3 genotype of individual participants. The CYP3A5*3 genotype affects the oral disposition of vardenafil significantly. The pharmacokinetic diversity of PDE5Is in relation to CYP3A5 genotype may lead to the clinical response variation and remains to be evaluated.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cross-Over Studies
  • Cytochrome P-450 CYP3A / genetics*
  • Genotype
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / pharmacokinetics
  • Male
  • Phosphodiesterase 5 Inhibitors / administration & dosage
  • Phosphodiesterase 5 Inhibitors / pharmacokinetics*
  • Piperazines / administration & dosage
  • Piperazines / pharmacokinetics
  • Purines / administration & dosage
  • Purines / pharmacokinetics
  • Pyrimidines / administration & dosage
  • Pyrimidines / pharmacokinetics*
  • Sildenafil Citrate
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacokinetics*
  • Sulfones / administration & dosage
  • Sulfones / pharmacokinetics
  • Triazines / administration & dosage
  • Triazines / pharmacokinetics
  • Vardenafil Dihydrochloride


  • Imidazoles
  • Phosphodiesterase 5 Inhibitors
  • Piperazines
  • Purines
  • Pyrimidines
  • Sulfonamides
  • Sulfones
  • Triazines
  • Vardenafil Dihydrochloride
  • Sildenafil Citrate
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A
  • udenafil