| Indication |
For the reduction of urinary obstruction and relief of associated
manifestations (eg. sensation of incomplete bladder emptying or
straining, urgency, interrupted or weak stream) in patients with
symptomatic beningn prostatic hyperplasia. |
| Pharmacodynamics |
Alfuzosin is a quinazoline-derivative alpha-adrenergic blocking
agent used to treat hypertension and benign prostatic hyperplasia.
Accordingly, alfuzosin is a selective inhibitor of the alpha(1) subtype
of alpha adrenergic receptors. In the human prostate, alfuzosin
antagonizes phenylephrine (alpha(1) agonist)-induced contractions, in vitro,
and binds with high affinity to the alpha1a adrenoceptor, which is
thought to be the predominant functional type in the prostate. Studies
in normal human subjects have shown that alfuzosin competitively
antagonized the pressor effects of phenylephrine (an alpha(1) agonist)
and the systolic pressor effect of norepinephrine. The antihypertensive
effect of alfuzosin results from a decrease in systemic vascular
resistance and the parent compound alfuzosin is primarily responsible
for the antihypertensive activity. |
| Mechanism of action |
Alfuzosin is a non-subtype specific alpha(1)-adrenergic blocking
agent that exhibits selectivity for alpha(1)-adrenergic receptors in the
lower urinary tract. Inhibition of these adrenoreceptors leads to the
relaxation of smooth muscle in the bladder neck and prostate, resulting
in the improvement in urine flow and a reduction in symptoms in benign
prostate hyperplasia. Alfuzosin also inhibits the vasoconstrictor effect
of circulating and locally released catecholamines (epinephrine and
norepinephrine), resulting in peripheral vasodilation. |
| Absorption |
Absorption is 50% lower under fasting conditions |
| Volume of distribution |
- 3.2 L/kg [healthy male middle-aged volunteers]
|
| Protein binding |
82%-90% |
| Metabolism |
Hepatic. Alfuzosin undergoes extensive metabolism by the liver,
with only 11% of the administered dose excreted unchanged in the urine.
Alfuzosin is metabolized by three metabolic pathways: oxidation,
O-demethylations, and N-dealkylation. The metabolites are not
pharmacologically active. CYP3A4 is the principal hepatic enzyme isoform
involved in its metabolism. |
| Route of elimination |
Following oral administration of 14C-labeled alfuzosin solution,
the recovery of radioactivity after 7 days (expressed as a percentage of
the administered dose) was 69% in feces and 24% in urine. |
| Half life |
10 hours |
| Clearance |
Not Available |
| Toxicity |
Side effects are dizziness (due to postural hypotension), upper respiratory tract infection, headache, and fatigue. |
