Abstract
1 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.
2 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 l kg-1 and 140 ml min-1) than in young subjects (1.0 l kg-1 and 83 ml min-1).
3 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).
4 Pressor response studies in the young subjects confirmed the α1-adrenoceptor antagonist activity of doxazosin with significant rightward shifts of the dose-response curves for the selective α1-adrenoceptor agonist phenylephrine.
5 Using the technique of concentration-effect analysis, both the degree of α1-adrenoceptor antagonism and the hypotensive effect can be correlated with the concentration of doxazosin in the `effect compartment'.
6 The gradual onset of action, the prolonged duration of hypotensive effect and the relatively long elimination half-life suggest that doxazosin may be a useful antihypertensive agent suitable for once-daily dosing.
Keywords: α1-adrenoceptor antagonism, doxazosin, pharmacodynamics, pharmacokinetics
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Selected References
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