Assessment of α1-adrenoceptor antagonists in benign prostatic hyperplasia based on the receptor occupancy theory

Kaori Ito, Hisakazu Ohtani, Yasufumi Sawada

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Aims: To assess the mechanistic relationship between doxazosin (α1-receptor antagonist) and receptor occupancy and a measure of pharmacological effect (Qmax, the maximum urinary flow rate) and to compare the mean receptor occupancy ratio at clinical doses of doxazosin, tamsulosin, terazosin and prazosin in benign prostatic hyperplasia (BPH). Methods: A ternary complex model, which described the mechanism of α1-receptor antagonists, was fitted to the pharmacological effects and receptor occupancy ratio data for doxazosin (standard tablet). In addition, mean receptor occupancy was calculated for other α1- receptor antagonists and the optimal receptor occupancy was evaluated. The clinical pharmacological effects of the controlled release formulation of doxazosin (doxazosin GITS) were estimated based on the receptor occupancy. Results: The mechanistic based model was able to describe the pharmacological effects of doxazosin. Regardless of the plasma concentrations or clinical dose of each drug, the results suggest that receptor occupancy is useful to assess quantitatively and compare the pharmacological effects of drugs with similar mechanisms of action. The clinical dosage for doxazosin GITS was estimated to be at least 8 mg and the stable pharmacological effect is expected based on the estimated receptor occupancy. Conclusions: A model for Qmax improvement in BPH based on the receptor occupancy theory was able to describe the clinical effects of the α1-receptor antagonists. Receptor occupancy is a useful index for predicting the clinical effects of α1-receptor antagonists.

Original languageEnglish
Pages (from-to)394-403
Number of pages10
JournalBritish journal of clinical pharmacology
Issue number4
Publication statusPublished - 2007 Apr
Externally publishedYes


  • Doxazosin
  • Pharmacodynamics
  • Pharmacokinetics
  • Receptor-binding

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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