After both oral and intravenous administration, doxazosin is extensively metabolized, with only about 5% of the administered dose excreted unchanged in urine. For single doses, oral bioavailability has been calculated to be about 65%; terminal elimination half-life is approximately 10 to 12 hours. In later multiple-dose studies in which doxazosin concentrations were measured beyond 24 hours after administration, the terminal elimination half-life was 22 hours. Clearance of doxazosin, presumably in the liver, involves the production of mainly O-demethylated and C-hydroxylated metabolites, and is low in comparison with hepatic blood flow. Protein binding is reported to be 98.3% in humans. Relatively low clearance (1.0 to 2.0 ml/min/kg) in association with a moderate volume of distribution (1.0 to 1.9 liters/kg) is responsible for doxazosin's relatively long plasma half-life. There is no evidence to suggest that active metabolites contribute significantly to the pharmacologic activity of doxazosin; both hypotensive effect and alpha-adrenoceptor inhibitor activity have been directly related to the concentration of doxazosin in blood. During long-term treatment, no significant changes in the disposition of doxazosin have been reported; with dosages up to the maximum clinically used dosage of 16 mg daily, there is no evidence of dose-dependent pharmacokinetics. Studies in elderly patients have shown no major pharmacokinetic differences. Overall, these pharmacokinetic results suggest that doxazosin is suitable for once-daily administration in the long-term treatment of patients with essential hypertension.