Clinical pharmacological studies with doxazosin.

Abstract

The clinical pharmacology of doxazosin is reviewed from studies in normotensive young (21-39 years) and elderly (62-89 years) subjects following oral (2 mg) and intravenous (1 mg) administration. In young subjects the mean bioavailability was 65% and the mean terminal elimination half-lives were 9.5 and 10.5 h following acute intravenous and oral administration respectively. These parameters were similar in the elderly with bioavailability of 69% and half-lives of 8.8 and 11.9 h. The apparent volume of distribution and clearance were significantly higher in elderly (1.7 1 kg-1 and 140 ml min-1) than in young subjects (1.01 kg-1 and 83 ml min-1). In both groups blood pressure reductions were most marked in the standing position and the maximum effect did not occur until 5-6 h, even after intravenous administration. The blood pressure reduction produced by doxazosin was associated in the young with a significant increase in heart rate to 108 beats min-1 (placebo, 82 beats min-1) but this increase was significantly attenuated in the elderly at 91 beats min-1 (placebo, 77 beats min-1). Pressor response studies in the young subjects confirmed the alpha 1-adrenoceptor antagonist activity of doxazosin with significant rightward shifts of the dose-response curves for the selective alpha 1-adrenoceptor agonist phenylephrine. Using the technique of concentration-effect analysis, both the degree of alpha 1-adrenoceptor antagonism and the hypotensive effect can be correlated with the concentration of doxazosin in the 'effect compartment'.(ABSTRACT TRUNCATED AT 250 WORDS)