European Journal of Clinical Pharmacology

, Volume 37, Issue 1, pp 53–58 | Cite as

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

  • M. G. Scott
  • A. H. Deering
  • M. T. McMahon
  • D. W. G. Harron
  • R. G. Shanks
Originals
  • 33 Downloads

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, tmax ranged from 1–2 h; Cmax (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 (t1/2) for alfuzosin was 3.4 h and 3.1 h after acute and chronic administration; (t1/2) 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.

Key words

alfuzosin prazosin alpha1-adrenoceptor antagonist noradrenaline pharmacokinetics pharmacodynamics healthy volunteers 

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Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • M. G. Scott
    • 2
  • A. H. Deering
    • 1
  • M. T. McMahon
    • 1
  • D. W. G. Harron
    • 1
  • R. G. Shanks
    • 1
  1. 1.Department of Therapeutics and PharmacologyThe Queen's University of BelfastBelfastNorthern Ireland
  2. 2.Department of PharmacyThe Queen's University of BelfastBelfastNorthern Ireland

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