Florun – Barter & Marcin Pharma

Florun 10 mg

Alfuzosin is an alpha-1 adrenergic antagonist used in the symptomatic management of benign prostatic hypertrophy (BPH).

Benign prostatic hyperplasia (BPH) refers to a benign growth or hyperplasia of the prostate and leads to lower urinary tract symptoms in men, such as urgency, frequency and changes to urine flow. The prevalence of BPH is as high as 50%-60% for males in their 60’s, and this prevalence increases to 80%-90% of those over 70. Alfuzosin is an alpha-1 adrenergic blocker used in the symptomatic treatment of BPH that works by relaxing the muscles in the prostate and bladder neck. It was initially approved by the FDA in 2003 and is marketed by several pharmaceutical companies.

Indication

Alfuzosin is used to treat the signs and symptoms of benign prostatic hyperplasia (BPH)

Pharmacodynamics

By selectively inhibiting alpha adrenergic receptors in the lower urinary tract, alfuzosin causes smooth muscle relaxation in the bladder neck and prostate, improving urine flow, thereby reducing BPH symptoms. Additionally, alfuzosin reduces the vasoconstrictor effect of catecholamines (epinephrine and norepinephrine), leading to peripheral vasodilation. This leads to a risk of postural hypotension/syncope, and prescribing information warns that caution should be exercised in patients who take nitrates, antihypertensives, or have experienced decreased blood pressure after using other medications.

Mechanism of Action

Alpha(1)-adrenoreceptors are found in the prostate, bladder base, bladder neck, prostatic capsule, and prostatic urethra; their activation may lead to contraction of smooth muscle and urinary symptoms in patients with BPH. Alfuzosin selectively binds to and inhibits alpha(1)-adrenergic receptors in the lower urinary tract. This leads to the relaxation of smooth muscle in both the prostate and bladder neck, resulting in the improvement in urine flow and a reduction of urinary symptoms.

Absorption

Alfuzosin is readily absorbed in the gastrointestinal tract and the absolute bioavailability under fed conditions is 49%.In patients over 75 years of age, alfuzosin is absorbed more rapidly and peak plasma levels are higher. One source mentions a bioavailability of 64%. After multiple doses under fed conditions, Cmax is achieved in 8 hours. Cmax and AUC0-24 values are about 13.6 ng/mL and 194 ng·h/mL, respectively. Steady-state plasma concentrations are achieved after the second dose and are 1.2 to 1.6 times higher than after a single dose. With the extended-release formulation, alfuzosin release is sustained over 20 hours with a rate of dissolution ranging between 2 and 12 hours.

Volume of Distribution

The volume of distribution of alfuzosin after intravenous administration in healthy volunteers is about 3.2 L/kg. Alfuzosin distributes heavily to the tissues of the prostate.

Protein Binding

The protein biding of alfuzosin is moderate and ranges from 82% to 90%. Alfuzosin is 68.2% bound to human serum albumin and 52.5% bound to human serum alpha-glycoprotein.

Metabolism

Alfuzosin undergoes extensive hepatic metabolism; only 11% of the administered dose is detected unchanged in the urine. Alfuzosin is metabolism occurs via three metabolic pathways: oxidation, O-demethylations, and N-dealkylation. Metabolites of alfuzosin are not pharmacologically active and CYP3A4 is main hepatic cytochrome enzyme responsible for its metabolism.

Route of Elimination

It is partially metabolised and excreted mainly in the bile and faeces. Following oral administration of a radiolabeled alfuzosin solution, the detection of radioactivity after one week was 69% in the feces and 24% in the urine.

Half-Life

The apparent elimination half-life of alfuzosin after oral administration is about 10 hours. The terminal half-life is 3-5 hours.

Clearance

Exercise caution if renal clearance is < 30 mL/min. The clearance of alfuzosin is increased in renal insufficiency (with or without dialysis), due to an increase in the free fraction.

Food Interactions

Take after a meal. Take alfuzosin after the same meal everyday. Do not take on an empty stomach.