Haemodynamic and pharmacokinetic evaluation of alfuzosin in man. A dose ranging study and comparison with prazosin.
In an open dose ranging study with random inclusion of placebo, alfuzosin (alpha 1-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Scott
M G
MG
Department of Therapeutics and Pharmacology, Queen's University of Belfast, Northern Ireland.
Deering
A H
AH
McMahon
M T
MT
Harron
D W
DW
Shanks
R G
RG
D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011224:Prazosin / Q000493:pharmacokinetics / Q000494:pharmacology*; D011799:Quinazolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011897:Random Allocation; D013997:Time Factors
D000959:Antihypertensive Agents; D011799:Quinazolines; C047638:alfuzosin; D009638:Norepinephrine; D011224:Prazosin