Biotransformation of sildenafil in the male rat: Evaluation of drug interactions with testosterone and carbamazepine

Ying Ku Lin, Ming Thau Sheu, Thau Zong Tzen, Hsiu O. Ho

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


The biotransformation of sildenafil to its major circulating metabolite, UK-103,320, was studied in male rat liver microsomes. The conversion of sildenafil to UK-103,320 by rat microsomes followed Michaelis-Menten kinetics, for which the parameters were Vmax = 1.96 μM/minand Km = 27.31 μM. Using substrates of CYP3A4 of testosterone and carbamazepine, the active sites on CYP3A4 responsible for metabolizing sildenafil were also evaluated. Sildenafil biotransformation was inhibited in the individual presence of testosterone and carbamazepine. The results showed drug interaction was observed in the sildenafil-testosterone and sildenafil-carbamazepine. Although testosterone and carbamazepine can inhibit sildenafil demethylation in concentration- and incubation time-dependent manners, sildenafil did not inhibit testosterone hydroxylation or carbamazepine epoxidation. These results may be explained by a model in which multiple substrates or ligands can concurrently bind to the active site of a single CYP3A4 molecule. However, the contribution of separate allosteric sites and conformational heterogeneity to the atypical kinetics of CYP3A4 cannot be ruled out in this study.

Original languageEnglish
Pages (from-to)1219-1226
Number of pages8
JournalDrug Development and Industrial Pharmacy
Issue number11
Publication statusPublished - Nov 2008


  • CYP3A4
  • Carbamazepine
  • Drug interaction
  • Sildenafil
  • Testosterone

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry


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