Alfuzosin Other names: Alfuzosin hydrochloride

Chemical formula: C₁₉H₂₇N₅O₄  Molecular mass: 389.449 g/mol  PubChem compound: 2092

Mechanism of action

Alfuzosin is an orally active quinazoline derivative. It is a selective, peripherally acting antagonist of postsynaptic alpha-1-adrenoceptors.

Pharmacodynamic properties

In vitro pharmacological studies have documented the selectivity of alfuzosin for the alpha-1-adrenoreceptors located in the prostate, bladder base and prostatic urethra.

Clinical manifestations of Benign Prostatic Hypertrophy are associated with infra vesical obstruction which is triggered by both anatomical (static) and functional (dynamic) factors. The functional component of obstruction arises from the tension of prostatic smooth muscle which is mediated by alpha-adrenoceptors. Activation of alpha-1-adrenoceptors stimulates smooth muscle contraction, thereby increasing the tone of the prostate, prostatic capsule, prostatic urethra and bladder base, and, consequently, increasing the resistance to bladder outflow. This in turn leads to outflow obstruction and possible secondary bladder instability.

Alpha-blockade decreases infra vesical obstruction via a direct action on prostatic smooth muscle.

In vivo, animal studies have shown that alfuzosin decreases urethral pressure and therefore, resistance to urine flow during micturition. Moreover, alfuzosin inhibits the hypertonic response of the urethra more readily than that of vascular muscle and shows functional uroselectivity in conscious normotensive rats by decreasing urethral pressure at doses that do not affect blood pressure.

In man, alfuzosin improves voiding parameters by reducing urethral tone and bladder outlet resistance, and facilitates bladder emptying.

In placebo controlled studies in BPH patients, alfuzosin:

  • significantly increases peak flow rate (Qmax) in patients with Qmax ≤15ml/s by a mean of 30%. This improvement is observed from the first dose,
  • significantly reduces the detrusor pressure and increases the volume producing a strong desire to void,
  • significantly reduces the residual urine volume.

These favourable urodynamic effects lead to an improvement of lower urinary tract symptoms ie. filling (irritative) as well as voiding (obstructive) symptoms.

Alfuzosin may cause moderate antihypertensive effects.

A lower frequency of acute urinary retention is observed in the alfuzosin treated patient than in the untreated patient.

Alfuzosin is not indicated for use in the paediatric population.

Pharmacokinetic properties

Prolonged-release formulation

The mean value of the relative bioavailability is 104.4 % versus the immediate release formulation (2.5 mg tid) in middle-aged healthy volunteers and the maximum plasma concentration is being achieved 9 hours after administration compared to 1 hour for the immediate release formulation.

The apparent elimination half-life is 9.1 hours.

Studies have shown that consistent pharmacokinetic profiles are obtained when the product is administered after a meal.

Under fed conditions, mean Cmax and Ctrough values are 13.6 (SD=5.6) and 3.2 (SD=1.6) ng/ml respectively. Mean AUC0-24 is 194 (SD=75) ng.h/ml. A plateau of concentration is observed from 3 to 14 hours with concentrations above 8.1 ng/ml (Cav) for 11 hours.

Compared to healthy middle aged volunteers, the pharmacokinetic parameters (Cmax and AUC) are not increased in elderly patients.

Compared to subjects with normal renal function, mean Cmax and AUC values are moderately increased in patients with renal impairment, without modification of the apparent elimination half-life. This change in the pharmacokinetic profile is not considered clinically relevant. Therefore, this does not necessitate a dosing adjustment.

The binding of alfuzosin to plasma proteins is about 90%. Alfuzosin undergoes extensive metabolism by the liver, with only 11 % of the parent compound being excreted unchanged in the urine. The majority of the metabolites (which are inactive) are excreted in the faeces (75 to 91 %).

The pharmacokinetic profile of alfuzosin is not affected by chronic cardiac insufficiency.

Metabolic interactions

CYP3A4 is the main hepatic enzyme isoform involved in the metabolism of alfuzosin.

Preclinical safety data

No data of therapeutic relevance.

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