Haemodynamic and pharmacokinetic evaluation of alfuzosin in man. A dose ranging study and comparison with prazosin

Summary

In an open dose ranging study with random inclusion of placebo, alfuzosin (α₁-adrenoceptor antagonist) 1, 2.5 and 5 mg was administered to 6 healthy volunteers, 3 of the volunteers received 10 mg alfuzosin.

Supine systolic blood (SBP) pressure was not reduced by alfuzosin although significant increases occurred in supine heart rate (HR) after 2.5 and 5 mg. In the standing position, SBP was reduced at 2 and 4 h with 5 mg alfuzosin; significant increases in HR occurred following 1, 2.5 and 5 mg at 2, 4, 6 and 8 h after administration. Exercise SBP was not reduced; diastolic blood pressure was significantly reduced at 4 and 6 h with 5 mg alfuzosin. More marked effects were seen in the 3 subjects who received 10 mg alfuzosin. After 1 and 5 mg, t_max ranged from 1–2 h; C_max (4.1 to 20.8 ng · ml⁻¹; AUC (0–24) 20 to 132 ng · ml⁻¹ · h (1 and 5 mg respectively) increased progressively with dose indicating dose dependent kinetics; no significant changes occurred in the visual analogue scale for sedation.

A comparison of alfuzosin 5 mg, prazosin 1 mg and placebo each administered for 4 days, indicated that alfuzosin did not significantly reduce standing SBP on either Day 1 or Day 4; prazosin reduced SBP at 2 and 4 h on Day 1 and 6 h on Day 4 compared to placebo. Standing HR was increased by alfuzosin at 2 h on Day 1 and Day 4; increases occurred with prazosin at 2, 4, 6 and 8 h on Day 1 and 6 h on Day 4.

Supine plasma noradrenaline increased with alfuzosin and prazosin at 2 and 4 h on Days 1 and 4; the increases were not significantly different. The plasma elimination half-life (t_1/2) for alfuzosin was 3.4 h and 3.1 h after acute and chronic administration; (t_1/2) for prazosin was 2.6 and 2.9 h.

In conclusion alfuzosin causes small reductions in systolic blood pressure, accompanied by a dose dependent increase in heart rate in the supine and standing position and following exercise.