The pharmacokinetics of doxazosin in patients with hypertension and renal impairment.

1. The pharmacokinetics of doxazosin, following a single oral dose (1 mg) and chronic oral dosing (doubling doses up to a maximum of 16 mg day-1), were studied in 18 patients with mild to moderate hypertension and stable renal function varying from normal to severely impaired. In addition, the effect of chronic administration of doxazosin on renal haemodynamics was evaluated. 2. Significant accumulation of doxazosin occurred with chronic dosing, but comparison of dose-adjusted AUC after single and chronic dosing suggested that there was no change in clearance or bioavailability during chronic administration. 3. There was no significant relationship between plasma elimination half-life or the AUC for doxazosin and the degree of renal impairment. 4. Symptomatic postural hypotension occurred in six patients following the initial dose of 1 mg doxazosin. Systolic and diastolic blood pressure measured 24 h after the previous dose were significantly reduced during chronic administration of doxazosin by a mean of 12/6 mm Hg supine and 10/7 mm Hg on standing. 5. During chronic administration of doxazosin, there was a significant reduction of 13% in glomerular filtration rate compared with pre-treatment, but no change in effective renal plasma flow.