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

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.