Alprostadil

Synonyms :
(11alpha,13e,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid, (13e)-(15S)-11alpha,15-Dihydroxy-9-oxoprost-13-enoate, 11alpha,15alpha-Dihydroxy-9-oxo-13-trans-prostenoic acid, Alprostadil, Alprostadil, Alprostadil, Alprostadil Alfadex, Alprostadilum, Befar, Caverject, Edex, Muse, PGE-1, PGE₁, PGE1 α-CD, Prostaglandin e1, Prostin vr

Status : approved

Therapeutic Classification

OTHER CARDIAC PREPARATIONS

CARDIOVASCULAR SYSTEM
CARDIAC THERAPY
OTHER CARDIAC PREPARATIONS

Description

Alprostadil is produced endogenously and causes vasodilation by means of a direct effect on vascular and ductus arteriosus (DA) smooth muscle, preventing or reversing the functional closure of the DA that occurs shortly after birth. This results in increased pulmonary or systemic blood flow in infants. In infants, it is used for palliative, not definitive, therapy to temporarily maintain the patency of the ductus arteriosus until corrective or palliative surgery can be performed in neonates who have congenital heart defects and who depend upon the patent ductus for survival. In adults, it is used for the treatment of erectile dysfunction due to neurogenic, vasculogenic, psychogenic, or mixed etiology.

Used

For palliative, not definitive, therapy to temporarily maintain the patency of the ductus arteriosus until corrective or palliative surgery can be performed in neonates who have congenital heart defects and who depend upon the patent ductus for survival. Also for the treatment of erectile dysfunction due to neurogenic, vasculogenic, psychogenic, or mixed etiology.

Mechanism Of Action

Alprostadil causes vasodilation by means of a direct effect on vascular and ductus arteriosus (DA) smooth muscle, preventing or reversing the functional closure of the DA that occurs shortly after birth. This is because, as a form of prostaglandinE1 (PGE1) it has multiple effects on blood flow. This results in increased pulmonary or systemic blood flow in infants. In cyanotic congenital heart disease, alprostadil’s actions result in an increased oxygen supply to the tissues. In infants with interrupted aortic arch or very severe aortic coarctation, alprostadil maintains distal aortic perfusion by permitting blood flow through the DA from the pulmonary artery to the aorta. In infants with aortic coarctation, alprostadil reduces aortic obstruction either by relaxing ductus tissue in the aortic wall or by increasing effective aortic diameter by dilating the DA. In infants with these aortic arch anomalies, systemic blood flow to the lower body is increased, improving tissue oxygen supply and renal perfusion. When administered by intracavernosal injection or as an intraurethral suppository, alprostadil acts locally to relax the trabecular smooth muscle of the corpora cavernosa and the cavernosal arteries. Swelling, elongation, and rigidity of the penis result when arterial blood rapidly flows into the corpus cavernosum to expand the lacunar spaces. The entrapped blood reduces the venous blood outflow as sinusoids compress against the tunica albuginea.

Dosage

Form Route Strength
Injection intravascular 500 ug/mL
Solution intravascular 500 mcg
Liquid intra-arterial; intravenous 500 mcg
Injection, powder, lyophilized, for solution intracavernous 10.5 ug/mL
Injection, powder, lyophilized, for solution intracavernous 20.5 ug/mL
Injection, powder, lyophilized, for solution intracavernous 41.1 ug/mL
Injection, powder, lyophilized, for solution intracavernous 5.4 ug/mL
Injection, powder, lyophilized, for solution intracavernous 10 ug/.5mL
Injection, powder, lyophilized, for solution intracavernous 20 ug/.5mL
Kit; liquid; powder for solution intracavernosal 11.9 mcg
Kit; liquid; powder for solution intracavernosal 23.2 mcg
Powder for solution intracavernosal 11.9 mcg
Powder for solution intracavernosal 23.2 mcg
Injection, powder, lyophilized, for solution intracavernous 10 ug/mL
Injection, powder, lyophilized, for solution intracavernous 20 ug/mL
Injection, powder, lyophilized, for solution intracavernous 40 ug/mL
Suppository urethral 1000 mcg
Suppository urethral 1000 ug
Suppository urethral 125 mcg
Suppository urethral 125 ug
Suppository urethral 250 mcg
Suppository urethral 250 ug
Suppository urethral 500 mcg
Suppository urethral 500 ug
Injection, solution intravascular; intravenous 500 ug/mL
Solution intra-arterial; intravenous 500 mcg
Cream topical 220 mcg
Cream topical 330 mcg

Pharmacodynamics

Alprostadil (prostaglandin E1) is produced endogenously to relax vascular smooth muscle and cause vasodilation. In adult males, the vasodilatory effects of alprostadil on the cavernosal arteries and the trabecular smooth muscle of the corpora cavernosa result in rapid arteriolar inflow and expansion of the lacunar spaces within the corpora. As the expanded corporal sinusoids are compressed against the tunica albuginea, venous outflow through the subtunical vessels is impeded and penile rigidity develops. This is referred to as the corporal veno-occlusive mechanism. In infants, the vasodilatory effects of alprostadil increase pulmonary or systemic blood flow.

Toxic Effect

Oral, mouse: LD50 = 186 mg/kg; Oral, rat: LD50 = 228 mg/kg. Apnea, bradycardia, pyrexia, hypotension, and flushing may be signs of drug overdosage.

Metabolism

Alprostadil must be infused continuously because it is very rapidly metabolized. As much as 80% of the circulating alprostadil may be metabolized in one pass through the lungs, primarily by beta- and omega-oxidation.

Absorption

The absolute bioavailability of alprostadil has not been determined.

Half Life

5 to 10 minutes (after a single dose), in healthy adults and neonates.

Protein Binding

Bound in plasma primarily to albumin (81% bound) and to a lesser extent alpha-globulin IV-4 fraction (55% bound).

Elimination Route

Alprostadil must be infused continuously because it is very rapidly metabolized. As much as 80% of the circulating alprostadil may be metabolized in one pass through the lungs, primarily by β- and ω-oxidation. The metabolites are excreted primarily by the kidney, and excretion is essentially complete within 24 hours after administration.

Chemical Classification

This compound belongs to the class of organic compounds known as prostaglandins and related compounds. These are unsaturated carboxylic acids consisting of a 20 carbon skeleton that also contains a five member ring, and are based upon the fatty acid arachidonic acid.

Prostaglandins and related compounds

Organic compounds

Lipids and lipid-like molecules

Fatty Acyls

Eicosanoids

Chemical Name

(11alpha,13e,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid

Brands

name Dosage form Country
Alprostadil injection US
Alprostadil Injection USP solution Canada
Alprostadil Injection, USP liquid Canada
Caverject injection, powder, lyophilized, for solution US
Caverject injection, powder, lyophilized, for solution US
Caverject injection, powder, lyophilized, for solution US
Caverject injection, powder, lyophilized, for solution US
Caverject Impulse injection, powder, lyophilized, for solution US
Caverject Impulse injection, powder, lyophilized, for solution US
Caverject Impulse injection, powder, lyophilized, for solution US
Caverject Impulse injection, powder, lyophilized, for solution US
Caverject Sterile Powder – Kit 11.9mcg /vial kit; liquid; powder for solution Canada
Caverject Sterile Powder – Kit 23.2mcg/vial kit; liquid; powder for solution Canada
Caverject Sterile Powder – Pws 11.9mcg/vial powder for solution Canada
Caverject Sterile Powder – Pws 23.2mcg/vial powder for solution Canada
Edex injection, powder, lyophilized, for solution US
Edex injection, powder, lyophilized, for solution US
Edex injection, powder, lyophilized, for solution US
Muse suppository Canada
Muse suppository US
Muse suppository US
Muse suppository US
Muse suppository US
Muse suppository Canada
Muse suppository Canada
Muse suppository Canada
Prostin VR PEDIATRIC injection, solution US
Prostin Vr Sterile Solution solution Canada
Vitaros cream Canada
Vitaros cream Canada

Drug Drug Interactions

  •  Avanafil  : Phosphodiesterase 5 Inhibitors may enhance the adverse/toxic effect of Alprostadil.
  •  Sildenafil  : Phosphodiesterase 5 Inhibitors may enhance the adverse/toxic effect of Alprostadil.
  •  Tadalafil  : Phosphodiesterase 5 Inhibitors may enhance the adverse/toxic effect of Alprostadil.
  •  Vardenafil  : Phosphodiesterase 5 Inhibitors may enhance the adverse/toxic effect of Alprostadil.

Calculated Property

kind Value Source
logP 3.04 ALOGPS
logS -3.6 ALOGPS
Water Solubility 7.88e-02 g/l ALOGPS
logP 3.59 ChemAxon
IUPAC Name 7-[(1R,2R,3R)-3-hydroxy-2-[(3S)-3-hydroxyoct-1-en-1-yl]-5-oxocyclopentyl]heptanoic acid ChemAxon
Traditional IUPAC Name alprostadil ChemAxon
Molecular Weight 354.481 ChemAxon
Monoisotopic Weight 354.240624198 ChemAxon
SMILES CCCCC[C@H](O)C=C[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O ChemAxon
Molecular Formula C20H34O5 ChemAxon
InChI InChI=1S/C20H34O5/c1-2-3-6-9-15(21)12-13-17-16(18(22)14-19(17)23)10-7-4-5-8-11-20(24)25/h12-13,15-17,19,21,23H,2-11,14H2,1H3,(H,24,25)/b13-12+/t15-,16+,17+,19+/m0/s1 ChemAxon
InChIKey InChIKey=GMVPRGQOIOIIMI-DWKJAMRDSA-N ChemAxon
Polar Surface Area (PSA) 94.83 ChemAxon
Refractivity 98.32 ChemAxon
Polarizability 41.88 ChemAxon
Rotatable Bond Count 13 ChemAxon
H Bond Acceptor Count 5 ChemAxon
H Bond Donor Count 3 ChemAxon
pKa (strongest acidic) 4.35 ChemAxon
pKa (strongest basic) -1.6 ChemAxon
Physiological Charge -1 ChemAxon
Number of Rings 1 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 1 ChemAxon
Ghose Filter 1 ChemAxon
MDDR-Like Rule 0 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • Prostaglandin E2 receptor EP2 subtype : in Human
  • Prostaglandin E2 receptor EP1 subtype : in Human