Pharmacokinetic and pharmacodynamic modelling of the alpha adrenoceptor antagonist doxazosin.

1. The pharmacokinetic and pharmacodynamic profiles of intravenous and oral doxazosin were investigated in 6 normotensive volunteers. 2. The pharmacokinetics of i.v. and oral doxazosin were fitted simultaneously and independently. The parameters derived were in good agreement with a mean elimination half-life of 539 +/- 75 min, bioavailability of 0.65 +/- 0.11 and clearance of 140 +/- 26 ml/min. 3. Pharmacokinetic-pharmacodynamic modelling indicated that the sensitivities to oral and i.v. doxazosin in individual subjects were in good agreement. 4. Based on these findings it is unlikely that doxazosin metabolites contribute significantly to the pharmacodynamic profile of doxazosin.