Alfuzosin hydrochloride (10 mg/kg, oral; single dosage) blocks the effects of phenylephrine on urethral and arterial pressure rises in less than six hours [1].

Animal/Disease Models: Male Wistar rat (250-450 g) [1].
Doses: 10 mg/kg
Route of Administration: Oral; single.
Experimental Results: Prostate concentrations increased to 4.1-8.6 times the plasma concentration.

Absorption, Distribution and Excretion
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.
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.
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.
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.
Following oral administration of (14)C-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. /Alfuzosin Hydrochloride/
The volume of distribution following intravenous administration in healthy male middle-aged volunteers was 3.2 L/kg. Results of in vitro studies indicate that alfuzosin is moderately bound to human plasma proteins (82% to 90%), with linear binding over a wide concentration range (5 to 5,000 ng/mL). /Alfuzosin Hydrochloride/
The extent of absorption is 50% lower under fasting conditions. Therefore, Uroxatral should be taken immediately following a meal. /Alfuzosin Hydrochloride/
The absolute bioavailability of Uroxatral 10 mg tablets under fed conditions is 49%. Following multiple dosing of 10 mg Uroxatral under fed conditions, the time to maximum concentration is 8 hours. Cmax and AUC0-24 are 13.6 (SD = 5.6) ng/mL and 194 (SD = 75) ng.h/mL, respectively.Uroxatral exhibits linear kinetics following single and multiple dosing up to 30 mg. Steady-state plasma levels are reached by with the second dose of Uroxatral administration. Steady-state alfuzosin plasma concentrations are 1.2- to 1.6-fold higher than those observed after a single administration. /Extended Release Alfuzosin Hydrochloride/
For more Absorption, Distribution and Excretion (Complete) data for ALFUZOSIN (6 total), please visit the HSDB record page.

---

Metabolism / Metabolites
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.
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-demethylation, and N-dealkylation. The metabolites are not pharmacologically active. CYP3A4 is the principal hepatic enzyme isoform involved in its metabolism. /Alfuzosin Hydrochloride/

---

Biological Half-Life
The apparent elimination half-life of alfuzosin after oral administration is about 10 hours. The terminal half-life is 3-5 hours.
Following oral administration of Uroxatral 10 mg tablets, the apparent elimination half-life is 10 hours. /Extended Release Alfuzosin Hydrochloride/

Hepatotoxicity
Alfuzosin has been associated with a low rate of serum aminotransferase elevations (
Likelihood score: C (probable cause of clinically apparent liver injury).

---

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.

---

Interactions
Single administration of 100 mg atenolol with a single dose of 2.5 mg of an immediate release alfuzosin tablet in eight healthy young male volunteers increased alfuzosin Cmax and AUC values by 28% and 21%, respectively. Alfuzosin increased atenolol Cmax and AUC values by 26% and 14%, respectively. In this study, the combination of alfuzosin with atenolol caused significant reductions in mean blood pressure and in mean heart rate.
Repeated administration of 1 g/day cimetidine increased both alfuzosin Cmax and AUC values by 20%.
Repeated co-administration of 240 mg/day of diltiazem, a moderately-potent inhibitor of CYP3A4, with 7.5 mg/day (2.5 mg three times daily) alfuzosin increased the Cmax and AUC0-24 of alfuzosin 1.5- and 1.3-fold, respectively. Alfuzosin increased the Cmax and AUC0-12 of diltiazem 1.4- fold. Although no changes in blood pressure were observed in this study, diltiazem is an antihypertensive medication and the combination of Uroxatral and antihypertensive medications has the potential to cause hypotension in some patients. /Alfuzosin Hydrochloride/
Repeated administration of 400 mg of ketoconazole, a potent inhibitor of CYP3A4, increased alfuzosin Cmax 2.3-fold and AUClast 3.2-fold following a single 10 mg dose of alfuzosin. Uroxatral should not be co-administered with potent inhibitors of CYP3A4,(e.g., ketoconazole, itraconazole, or ritonavir). /Alfuzosin Hydrochloride/
For more Interactions (Complete) data for ALFUZOSIN (9 total), please visit the HSDB record page.

[1]. Relationship between the effects of alfuzosin on rat urethral and blood pressures and its tissue concentrations. Life Sci. 1998;63(3):169-76.

[2]. Alfuzosin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in benign prostatic hyperplasia. Drugs. 1993 Mar;45(3):410-29.

Alfuzosin is a monocarboxylic acid amide, a tetrahydrofuranol and a member of quinazolines. It has a role as an antineoplastic agent, an antihypertensive agent and an alpha-adrenergic antagonist.
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.
Alfuzosin is an alpha-Adrenergic Blocker. The mechanism of action of alfuzosin is as an Adrenergic alpha-Antagonist.
Alfuzosin is a nonselective alpha-1 adrenergic antagonist used in the therapy of benign prostatic hypertrophy. Alfuzosin is associated with a low rate of transient serum aminotransferase elevations and with rare instances of clinically apparent acute liver injury.
Alfuzosin is a synthetic quinazoline compound with smooth muscle relaxing activity. Alfuzosin selectively binds to and antagonizes alpha-1-adrenergic receptors in smooth muscle of the bladder neck and prostate, thereby relaxing the smooth muscle and decreasing the obstruction and urethral resistance seen with benign prostate hyperplasia (BPH) and prostate cancer. This agent also blocks alpha-1-adrenergic receptors in peripheral vascular smooth muscle, which leads to vasodilatation and a subsequent decrease in peripheral vascular resistance.
See also: Alfuzosin Hydrochloride (has salt form).

---

Drug Indication
Alfuzosin is used to treat the signs and symptoms of benign prostatic hyperplasia (BPH).
FDA Label

---

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.
Alfuzosin hydrochloride, a quinazoline-derivative alpha1-adrenergic blocking agent, is structurally and pharmacologically related to prazosin. Alfuzosin is a non-subtype-specific alpha1-adrenergic blocking agent that exhibits selectivity for alpha1-adrenergic receptors in the lower urinary tract (e.g., bladder base, bladder neck, prostate, prostatic capsule, prostatic urethra). Blockade of these adrenoreceptors can cause relaxation of smooth muscle in the bladder neck and prostate, resulting in improvement in urine flow and a reduction in symptoms of benign prostatic hyperplasia (BPH).

---

Therapeutic Uses
Antihypertensive
Alfuzosin hydrochloride is used for the symptomatic management of benign prostatic hyperplasia (BPH, benign prostatic hypertrophy). Alfuzosin relieves moderate to severe irritative (e.g., frequency, urgency, nocturia) and obstructive (e.g., hesitancy, interrupted or weak stream, sensation of incomplete bladder emptying or straining) manifestations and improves urinary flow rates in a substantial proportion of patients.
Uroxatal is not indicated for the treatment of hypertension. /Alfuzosin Hydrochloride/

---

Drug Warnings
In a study of QT effect in 45 healthy males, the QT effect appeared less with alfuzosin 10 mg than with 40 mg, and the effect of alfuzosin 40 mg did not appear as large as that of the active control moxifloxacin at its therapeutic dose. This observation should be considered in clinical decisions to prescribe Uroxatral for patients with a known history of QT prolongation or patients who are taking medications known to prolong QT, although there has been no signal of Torsades de Pointe in the extensive postmarketing experience with alfuzosin outside the United States. There are no known PK/PD studies of the effects of other alpha blockers on cardiac repolarization. /Alfuzosin Hydrochloride/
Postural hypotension with or without symptoms (e.g., dizziness) may develop within a few hours following administration of Uroxatral (alfuzosin HCl extended-release tablets). As with other alpha-blockers, there is a potential for syncope. Patients should be warned of the possible occurrence of such events and should avoid situations where injury could result should syncope occur. Care should be taken when Uroxatral is administered to patients with symptomatic hypotension or patients who have had a hypotensive response to other medications.
Carcinoma of the prostate and benign prostatic hyperplasia cause many of the same symptoms. These two diseases frequently coexist. Therefore, patients thought to have benign prostatic hyperplasia should be examined prior to starting therapy with Uroxatral (alfuzosin HCl extended-release tablets) to rule out the presence of carcinoma of the prostate.
If symptoms of angina pectoris should newly appear or worsen, Uroxatral should be discontinued. /Extended Release Alfuzosin Hydrochloride/
For more Drug Warnings (Complete) data for ALFUZOSIN (16 total), please visit the HSDB record page.

---

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.

C19H27N5O4

389.44878

389.206

81403-80-7

Alfuzosin hydrochloride;81403-68-1;Alfuzosin-d7;1133386-93-2;Alfuzosin-13C,d3;Alfuzosin-d3;1006724-55-5

2092

White to off-white solid powder

1.3±0.1 g/cm3

1.621

-1

2

8

8

28

511

0

WNMJYKCGWZFFKR-UHFFFAOYSA-N

InChI=1S/C19H27N5O4/c1-24(8-5-7-21-18(25)14-6-4-9-28-14)19-22-13-11-16(27-3)15(26-2)10-12(13)17(20)23-19/h10-11,14H,4-9H2,1-3H3,(H,21,25)(H2,20,22,23)

N-[3-[(4-amino-6,7-dimethoxyquinazolin-2-yl)-methylamino]propyl]oxolane-2-carboxamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 50 mg/mL (~128.39 mM)

Solubility in Formulation 1: ≥ 3 mg/mL (7.70 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 3 mg/mL (7.70 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 3 mg/mL (7.70 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)