Doxazosin, an alpha 1-adrenoceptor antagonist: pharmacokinetics and concentration-effect relationships in man

Br J Clin Pharmacol. 1983 Jun;15(6):719-25. doi: 10.1111/j.1365-2125.1983.tb01556.x.

Abstract

The effects of single doses of doxazosin, a quinazoline derivative similar to prazosin, were studied in six normotensive volunteers. Both 1 mg (i.v.) or 2 mg (oral) doxazosin caused a fall in blood pressure which was most apparent in the erect posture at 5-6 h following drug administration. The maximum fall in blood pressure following i.v. doxazosin was from 123/81 to 106/69 mm Hg associated with a rise in heart rate from 81 to 107 beats/min. The terminal elimination half-life following oral and intravenous doxazosin was about 9 h. Pressor responsiveness to the alpha 1-adrenoceptor agonist, phenylephrine, showed no significant difference between oral and i.v. doxazosin suggesting that the route of administration did not influence alpha 1-adrenoceptor antagonism at the doses used. Using a pharmacodynamic modelling technique in individual subjects, there was a significant correlation between the change in doxazosin concentration in the effect compartment and its hypotensive effect. With the modelling technique it was possible to show a significant correlation between the pressor responsiveness to the alpha 1-adrenoceptor agonist phenylephrine and the concentration of doxazosin in the effect compartment. This is consistent with the concept that the hypotensive effect of doxazosin is mediated by alpha 1-adrenoceptor blockade.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adrenergic alpha-Antagonists / blood
  • Adrenergic alpha-Antagonists / pharmacology*
  • Adult
  • Blood Pressure / drug effects
  • Dose-Response Relationship, Drug
  • Doxazosin
  • Half-Life
  • Heart Rate / drug effects
  • Humans
  • Kinetics
  • Male
  • Phenylephrine / pharmacology
  • Prazosin / analogs & derivatives
  • Prazosin / blood
  • Prazosin / pharmacology*
  • Quinazolines / pharmacology*

Substances

  • Adrenergic alpha-Antagonists
  • Quinazolines
  • Phenylephrine
  • Doxazosin
  • Prazosin