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Pharmacotherapeutic Group: Alpha-Blockers. ATC code: G04CA01(G: genitourinary system and sex hormones).
Pharmacology: Pharmacodynamics: Alfuzosin is a quinazoline derivative, active by the oral route. It is an uroselective antagonist of post-synaptic α1-adrenoceptors located in the prostate, bladder base, bladder neck, prostatic capsule, and prostatic urethra.
Alfuzosin hydrochloride blocks α1-adrenoceptors leading to a relaxation of the smooth muscle in the bladder neck and prostate.
In animal studies, alfuzosin was shown to be functionally uroselective by preferentially decreasing urethral blood pressure over arterial blood pressure. In human tissue, in vitro, alfuzosin has induced preferential α1-adrenoceptor antagonist activity on prostatic cells relative to renal artery cells.
In placebo-controlled clinical studies in patients with BPH, alfuzosin hydrochloride was shown to: significantly increase urine peak flow rate (Qmax) by 30% which is observed after the first dose; significantly reduce detrusor pressure and increase bladder capacity; significantly reduce residual urine volume.
These favourable urodynamic effects lead to an improvement of lower tract irritative and obstructive symptoms without any deleterious effect on sexual function.
In the ALFAUR study, the effect of alfuzosin on return to voiding was assessed in 357 men over the age of 50 presenting a first painful episode of acute urinary retention (AUR) related to benign prostatic hypertrophy (BPH) with a residual urine volume of between 500 and 1500 ml following insertion of a catheter and for the first hour after catheterisation. In this multicentre, randomised, doubleblind study in two parallel groups comparing 10 mg/day alfuzosin LP with placebo, evaluation of return to voiding was conducted 24 hours after removal of the catheter, in the morning, after at least two days of alfuzosin treatment. Treatment with alfuzosin significantly increased (p = 0.012) the rate of return to voiding after catheter removal in patients having suffered a first episode of AUR, i.e. 146 returns to voiding (61.9%) in the alfuzosin group versus 58 (47.9%) in the placebo group.
Pharmacokinetics: Bioavailability is reduced when alfuzosin hydrochloride is administered under fasting conditions.
Alfuzosin hydrochloride is moderately bound to plasma proteins with the free fraction accounting for 13.3% in healthy volunteers.
Alfuzosin hydrochloride undergoes metabolism by the liver, with only 11% of the parent compound being excreted as unchanged in the urine. The metabolites which are all inactive are eliminated in the urine (15-30%) and feces (75-91%). Most of the metabolites (which are inactive) are excreted in the faeces (75 to 90%).
Following intravenous or oral administration, the elimination of alfuzosin hydrochloride is characterized, in healthy young subjects and in the target population, by a terminal half-life of about 4.8 hours and a total clearance of 0.3 L/h/kg.
The apparent half-life of alfuzosin hydrochloride is increased to 9.1 hours in healthy middle aged volunteers and to 10.1 hours in elderly volunteers.
Compared to healthy middle-aged volunteers, the pharmacokinetic parameters of alfuzosin hydrochloride (Cmax and AUC) are not increased in elderly patients.
The pharmacokinetic profile of alfuzosin is not modified in the event of chronic heart failure.
Compared to subjects with normal renal function, the mean Cmax and AUC values of alfuzosin hydrochloride are moderately increased (1.5 to 1.6 fold) in patients with various stages of renal impairment, with no change in the apparent elimination half-life. This change in the pharmacokinetic profile is not considered clinically relevant; and therefore, does not necessitate a dosing adjustment. Alfuzosin hydrochloride prolonged-release tablet has not been evaluated in patients with end-stage renal disease.
