Objectives. To investigate the relationship among doxazosin dose, plasma concentration, and clinical response in 248 hypertensive men with benign prostatic hyperplasia (BPH) in a 16-week, placebo-controlled, double-blind study.

Methods. After a 2-week placebo run-in period, patients were randomized to treatment with either doxazosin (titrated to doses of 2, 4, 8, or 12 mg once daily) or placebo. After 6, 10, and 14 weeks, plasma concentrations of doxazosin were measured at 2 to 6 hours (peak) and approximately 24 hours (trough) after dosing. Changes in maximal urinary flow rate (Qmax) compared with baseline were measured at the same time points. Patients recorded their symptoms in a daily diary and completed a questionnaire at weeks 2, 8, and 16 to assess both obstructive and irritative BPH symptoms. In addition, BPH symptoms were assessed by the investigator at each study visit.

Results. Steady-state peak and trough plasma doxazosin concentrations were achieved by 6 weeks of therapy and were maintained between 6 and 14 weeks of active treatment. Peak and trough plasma concentrations increased linearly within the dose range of 2 to 12 mg and were positively correlated with a corresponding mean improvement in Qmax (P = 0.001 and P = 0.008, respectively), consistent with a 24- hour once-daily dosing of doxazosin. Clinical response to doxazosin plateaued at peak and trough plasma concentrations of between 60 and 80 ng/mL and 25 ng/mL, respectively, corresponding to a dose of 8 mg daily. Patient assessment of obstructive BPH symptoms showed significant improvement in the 4- and 8-mg doxazosin treatment groups compared with placebo.

Conclusions. In patients with BPH, both doxazosin plasma concentration and Qmax increased linearly with increasing dose, in the range of 2 to 8 mg daily. The maximal therapeutic dosage of doxazosin would appear to be 8 mg in this group of BPH patients. Further studies are required to support these findings.