Single-Dose and Steady-State Pharmacokinetics of Doxazosin Given in Combination with Chlorothiazide to Hypertensive Subjects

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Abstract
The pharmacokinetics of doxazosin were determined in hypertensive subjects after a single dose of 1mg, and at steady-state while receiving doses of 1, 2, 4 and 8mg of the drug daily. Chlorothiazide 500mg once daily was administered as additional therapy throughout the study. After a single dose doxazosin was rapidly absorbed, with peak plasma drug concentrations (Cmax) occurring after 2.1 ± 0.4 hours. The elimination half-life in plasma was 10.7 ± 1.2 hours. These parameters remained essentially unchanged during maintenance administration of doxazosin at each of the dose levels. Calculations of Cmax and area under the concentration-time curve (A UC0→∞) indicated that the pharmacokinetic disposition of the drug remained linear over the dose range 1 to 8mg.