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Identification
NameAlprostadil
Accession NumberDB00770  (APRD00785)
Typesmall molecule
Groupsapproved, investigational
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.

Structure
Thumb
Synonyms
SynonymLanguageCode
AlprostadilGermanINN
AlprostadilFrenchINN
AlprostadilSpanishINN
Alprostadil AlfadexNot AvailableBAN
AlprostadilumLatinINN
PGE₁ Not AvailableIS
PGE1 α-CDNot AvailableIS
SaltsNot Available
Brand names
NameCompany
AlistaNot Available
AlprostadilBedford
AlprostanZentiva
AlprostapintCloster
AlprostarRecordati
AlprostinPfizer
Alprox-TDNot Available
AltesilTaiyo Pharmaceutical
AlyprostFuji Yakuhin
ApistandinFuji Yakuhin
AplicavLibbs
BefarNexmed
BolesiYaoyou Pharmaceutical
BondilMeda
CardiobronFada
CaverjectPfizer
Caverject DCPfizer
Caverject DualPfizer
EdexSchwarz
EglandinWelfide
FemproxNot Available
Kai TongJilin Yuhua Pharmaceutical Co.
KaishiTide Pharmaceutical
KaronZentiva
LipleTanabe Mitsubishi Pharma
MinprogPfizer
MuseAstraZeneca
PaluxTaisho Yakuhin
PridaxGebro
PrinkTaiyo Pharmaceutical
Prolisina VRPfizer
ProstandinOno Yakuhin
ProstavasinSchwarz
Prostin VRPfizer
Prostin VR PediatricPfizer
ProstivasPfizer
SugiranEsteve
TandetronTakata Seiyaku
TopiglanNot Available
VasaprostanBayer
VasoprostUCB
VasostenoonKevelt
ViridalUCB
Brand mixtures
Brand NameIngredients
Caverject Sterile Powder - Kit 11.9mcg /VialAlprostadil + Water
Caverject Sterile Powder - Kit 23.2mcg/VialAlprostadil + Water
CategoriesNot Available
CAS number745-65-3
WeightAverage: 354.481
Monoisotopic: 354.240624198
Chemical FormulaC20H34O5
InChI KeyInChIKey=GMVPRGQOIOIIMI-DWKJAMRDSA-N
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
IUPAC Name
7-[(1R,2R,3R)-3-hydroxy-2-[(3S)-3-hydroxyoct-1-en-1-yl]-5-oxocyclopentyl]heptanoic acid
SMILES
CCCCC[C@H](O)C=C[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassEicosanoids
SubclassProstaglandins and related compounds
Direct parentProstaglandins and related compounds
Alternative parentsKeto Fatty Acids; Carbocyclic Fatty Acids; Fatty Alcohols; Unsaturated Fatty Acids; Secondary Alcohols; Ketones; Cyclic Alcohols and Derivatives; Enolates; Carboxylic Acids; Polyamines
Substituentsfatty alcohol; cyclic alcohol; secondary alcohol; ketone; polyamine; carboxylic acid derivative; enolate; carboxylic acid; alcohol; carbonyl group
Classification descriptionThis compound belongs to the prostaglandins and related compounds. These are unsaturated carboxylic acids consisting of of a 20 carbon skeleton that also contains a five member ring, and are based upon the fatty acid arachidonic acid.
Pharmacology
IndicationFor 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.
PharmacodynamicsAlprostadil (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.
Mechanism of actionAlprostadil 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.
AbsorptionThe absolute bioavailability of alprostadil has not been determined.
Volume of distributionNot Available
Protein bindingBound in plasma primarily to albumin (81% bound) and to a lesser extent alpha-globulin IV-4 fraction (55% bound).
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.

Route of eliminationAlprostadil 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.
Half life5 to 10 minutes (after a single dose), in healthy adults and neonates.
ClearanceNot Available
ToxicityOral, mouse: LD50 = 186 mg/kg; Oral, rat: LD50 = 228 mg/kg. Apnea, bradycardia, pyrexia, hypotension, and flushing may be signs of drug overdosage.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9815
Blood Brain Barrier + 0.8704
Caco-2 permeable + 0.5245
P-glycoprotein substrate Substrate 0.5554
P-glycoprotein inhibitor I Non-inhibitor 0.9202
P-glycoprotein inhibitor II Non-inhibitor 0.8983
Renal organic cation transporter Non-inhibitor 0.9064
CYP450 2C9 substrate Non-substrate 0.8211
CYP450 2D6 substrate Non-substrate 0.8834
CYP450 3A4 substrate Non-substrate 0.5292
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9502
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.8309
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9725
Ames test Non AMES toxic 0.9387
Carcinogenicity Non-carcinogens 0.9201
Biodegradation Ready biodegradable 0.6056
Rat acute toxicity 2.9631 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9087
hERG inhibition (predictor II) Non-inhibitor 0.9138
Pharmacoeconomics
Manufacturers
  • Bedford laboratories div ben venue laboratories inc
  • Teva parenteral medicines inc
  • Pfizer inc
  • Pharmacia and upjohn co
  • Schwarz pharma ag
  • Vivus inc
Packagers
Dosage forms
FormRouteStrength
LiquidIntravenous
SolutionIntra-arterial
SuppositoryUrethral
Prices
Unit descriptionCostUnit
Alprostadil powder5049.0USDg
Edex Cartridge 6 Pack 40 mcg Kit Box412.4USDbox
Caverject 6 40 mcg Solution Box341.78USDbox
Edex 6 Pack 20 mcg Kit Box301.0USDbox
Caverject 6 20 mcg Solution, 1 Box Contains 6 Vials Box272.05USDbox
Prostin Vr 500 mcg/ml266.72USDml
Edex Cartridge 6 Pack 10 mcg Kit Box233.65USDbox
Edex Cartridge 2 Pack 40 mcg Kit Box135.23USDbox
Edex 40 mcg cartridge kit132.18USDkit
Prostin vr 500 mcg/ml ampul108.0USDml
Edex 2 Pack 20 mcg Kit Box97.47USDbox
Edex 20 mcg cartridge kit96.47USDkit
Edex Cartridge 2 Pack 10 mcg Kit Box77.22USDbox
Edex 10 mcg cartridge kit74.88USDkit
Alprostadil 500 mcg/ml vial66.0USDml
Caverject Impulse 1 Box = 2 Blister Trays, 20 mcg47.77USDbox
Caverject impulse 20 mcg kit46.66USDeach
Caverject Impulse 1 Box = 2 Blister Trays, 10 mcg37.51USDbox
Muse 1000 mcg Pellets36.97USDpellet
Caverject impulse 10 mcg kit36.23USDeach
Muse 1000 mcg urethral suppository35.54USDsuppository
Muse 500 mcg Pellets34.23USDpellet
Muse 500 mcg urethral suppository32.92USDsuppository
Muse 250 mcg Pellets31.99USDpellet
Muse 250 mcg urethral suppository30.76USDsuppository
Muse 125 mcg Pellets30.56USDpellet
Muse 125 mcg urethral suppository29.39USDsuppository
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States58860391996-03-232016-03-23
United States57730201993-04-252010-04-25
Canada13353461995-04-252012-04-25
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point115-116 °CNot Available
water solubility26.7 mg/LNot Available
logP3.20AVDEEF,A ET AL. (1995)
pKa4.85 (at 25 °C)AVDEEF,A ET AL. (1995)
Predicted Properties
PropertyValueSource
water solubility7.88e-02 g/lALOGPS
logP3.04ALOGPS
logP3.59ChemAxon
logS-3.6ALOGPS
pKa (strongest acidic)4.35ChemAxon
pKa (strongest basic)-1.6ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count3ChemAxon
polar surface area94.83ChemAxon
rotatable bond count13ChemAxon
refractivity98.32ChemAxon
polarizability41.88ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
Spectra
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00180
KEGG CompoundC04741
PubChem Compound5280723
PubChem Substance46508029
ChemSpider131636
ChEBI15544
ChEMBLCHEMBL495
Therapeutic Targets DatabaseDAP001490
PharmGKBPA448334
IUPHAR1882
Guide to Pharmacology1882
Drug Product Database2241680
RxListhttp://www.rxlist.com/cgi/generic/alprostadil.htm
Drugs.comhttp://www.drugs.com/cdi/alprostadil.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/cav1073.shtml
WikipediaAlprostadil
ATC CodesC01EA01G04BE01
AHFS Codes
  • 24:12.92
PDB EntriesNot Available
FDA labelshow(283 KB)
MSDSshow(74.3 KB)
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

1. Prostaglandin E2 receptor EP2 subtype

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Prostaglandin E2 receptor EP2 subtype P43116 Details

References:

  1. Dijkstra BG, Schneemann A, Hoyng PF: Flow after prostaglandin E1 is mediated by receptor-coupled adenylyl cyclase in human anterior segments. Invest Ophthalmol Vis Sci. 1999 Oct;40(11):2622-6. Pubmed
  2. Takahashi HK, Iwagaki H, Tamura R, Katsuno G, Xue D, Sugita S, Mori S, Yoshino T, Tanaka N, Nishibori M: Differential effect of prostaglandins E1 and E2 on lipopolysaccharide-induced adhesion molecule expression on human monocytes. Eur J Pharmacol. 2005 Apr 11;512(2-3):223-30. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Prostaglandin E2 receptor EP1 subtype

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Prostaglandin E2 receptor EP1 subtype P34995 Details

References:

  1. Norel X, de Montpreville V, Brink C: Vasoconstriction induced by activation of EP1 and EP3 receptors in human lung: effects of ONO-AE-248, ONO-DI-004, ONO-8711 or ONO-8713. Prostaglandins Other Lipid Mediat. 2004 Oct;74(1-4):101-12. Pubmed
  2. Takahashi HK, Iwagaki H, Tamura R, Xue D, Sano M, Mori S, Yoshino T, Tanaka N, Nishibori M: Unique regulation profile of prostaglandin e1 on adhesion molecule expression and cytokine production in human peripheral blood mononuclear cells. J Pharmacol Exp Ther. 2003 Dec;307(3):1188-95. Epub 2003 Oct 15. Pubmed
  3. Ito Y, Murai Y, Ishibashi H, Onoue H, Akaike N: The prostaglandin E series modulates high-voltage-activated calcium channels probably through the EP3 receptor in rat paratracheal ganglia. Neuropharmacology. 2000 Jan 4;39(2):181-90. Pubmed
  4. Matlhagela K, Taub M: Involvement of EP1 and EP2 receptors in the regulation of the Na,K-ATPase by prostaglandins in MDCK cells. Prostaglandins Other Lipid Mediat. 2006 Mar;79(1-2):101-13. Epub 2006 Jan 27. Pubmed
  5. Tokuda H, Kozawa O, Miwa M, Uematsu T: p38 mitogen-activated protein (MAP) kinase but not p44/p42 MAP kinase is involved in prostaglandin E1-induced vascular endothelial growth factor synthesis in osteoblasts. J Endocrinol. 2001 Sep;170(3):629-38. Pubmed

1. Multidrug resistance-associated protein 5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance-associated protein 5 O15440 Details

References:

  1. Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, Wijnholds J, Borst P: The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9. Epub 2003 Jun 30. Pubmed

2. Solute carrier organic anion transporter family member 2B1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 2B1 O94956 Details

References:

  1. Nishio T, Adachi H, Nakagomi R, Tokui T, Sato E, Tanemoto M, Fujiwara K, Okabe M, Onogawa T, Suzuki T, Nakai D, Shiiba K, Suzuki M, Ohtani H, Kondo Y, Unno M, Ito S, Iinuma K, Nunoki K, Matsuno S, Abe T: Molecular identification of a rat novel organic anion transporter moat1, which transports prostaglandin D(2), leukotriene C(4), and taurocholate. Biochem Biophys Res Commun. 2000 Sep 7;275(3):831-8. Pubmed

3. Solute carrier organic anion transporter family member 3A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 3A1 Q9UIG8 Details

References:

  1. Adachi H, Suzuki T, Abe M, Asano N, Mizutamari H, Tanemoto M, Nishio T, Onogawa T, Toyohara T, Kasai S, Satoh F, Suzuki M, Tokui T, Unno M, Shimosegawa T, Matsuno S, Ito S, Abe T: Molecular characterization of human and rat organic anion transporter OATP-D. Am J Physiol Renal Physiol. 2003 Dec;285(6):F1188-97. Pubmed
  2. Adachi H, Suzuki T, Abe M, Asano N, Mizutamari H, Tanemoto M, Nishio T, Onogawa T, Toyohara T, Kasai S, Satoh F, Suzuki M, Tokui T, Unno M, Shimosegawa T, Matsuno S, Ito S, Abe T: Molecular characterization of human and rat organic anion transporter OATP-D. Am J Physiol Renal Physiol. 2003 Dec;285(6):F1188-97. Pubmed

4. Multidrug resistance-associated protein 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance-associated protein 4 O15439 Details

References:

  1. Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, Wijnholds J, Borst P: The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9. Epub 2003 Jun 30. Pubmed

5. Solute carrier organic anion transporter family member 2A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 2A1 Q92959 Details

References:

  1. Lu R, Kanai N, Bao Y, Schuster VL: Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA(hPGT). J Clin Invest. 1996 Sep 1;98(5):1142-9. Pubmed
  2. Kanai N, Lu R, Satriano JA, Bao Y, Wolkoff AW, Schuster VL: Identification and characterization of a prostaglandin transporter. Science. 1995 May 12;268(5212):866-9. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12