Premium
Clinical pharmacological studies with doxazosin.
Author(s) -
Elliott HL,
Meredith PA,
Vincent J,
Reid JL
Publication year - 1986
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1986.tb02850.x
Subject(s) - doxazosin , phenylephrine , blood pressure , medicine , placebo , heart rate , mean blood pressure , antagonist , oral administration , bioavailability , atenolol , anesthesia , pharmacology , receptor , alternative medicine , pathology
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)