Objectives: To assess the efficacy and safety of a new prolonged release formulation of the uroselective α1–blocker alfuzosin for a once–daily dosing regimen in patients with lower urinary tract symptoms (LUTS) suggestive of symptomatic benign prostatic hyperplasia (BPH). Methods: After a 1–month run–in period, 447 patients were randomly allocated in a double–blind placebo–controlled study to receive alfuzosin 10 mg once daily (n = 143), alfuzosin 2.5 mg thrice daily (n = 150) or placebo (n = 154) for 3 months. At inclusion, 46% of the randomised population had concomitant cardiovascular disease and 30% received an antihypertensive treatment. Uroflowmetry was performed close to trough plasma concentration of alfuzosin once daily to demonstrate the 24–hour coverage with this formulation. Results: Both alfuzosin formulations significantly improved urinary symptoms versus placebo assessed using the International Prostate Symptom Score (alfuzosin 10 mg once daily: –6.9; alfuzosin 2.5 mg thrice daily: –6.4; placebo: –4.9, p = 0.005). Peak flow rate increased significantly with alfuzosin 10 mg once daily (+2.3 ml/s, p = 0.03 vs. placebo) and with alfuzosin 2.5 mg thrice daily (+3.2ml/s, p<0.0001 vs. placebo) compared to placebo (+1.4 ml/s). Overall both formulations of alfuzosin were well tolerated in comparison with placebo. In addition, vasodilatory adverse events appeared to be less frequent with the once daily than the thrice daily formulation (6.3 vs. 9.4%, respectively). No first–day effect was reported with alfuzosin once daily and the effect on blood pressure did not differ from those observed in placebo, both in normotensive and hypertensive patients. No specific sexual dysfunction including ejaculation disorder was reported in the alfuzosin 10 mg once–daily group. Conclusion: The new once–daily formulation of alfuzosin administered at a dose of 10 mg daily is an effective 24–hour treatment of LUTS associated with BPH. Alfuzosin is as effective as the immediate formulation and shows a better cardiovascular safety. The better safety profile enables the same dose to be used in all patients, providing the patients with the benefits of a once–daily administration.

Keywords:
Prolonged–release formulation alfuzosin, Uroselective α1–blocker, Benign prostatic hyperplasia, Placebo
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