Verteporfin

Identification

Name
Verteporfin
Accession Number
DB00460  (APRD01290)
Type
Small Molecule
Groups
Approved, Investigational
Description

Verteporfin, otherwise known as benzoporphyrin derivative (trade name Visudyne®), is a medication used as a photosensitizer for photodynamic therapy to eliminate the abnormal blood vessels in the eye associated with conditions such as the wet form of macular degeneration. Verteporfin accumulates in these abnormal blood vessels and, when stimulated by nonthermal red light with a wavelength of 693 nm in the presence of oxygen, produces highly reactive short-lived singlet oxygen and other reactive oxygen radicals, resulting in local damage to the endothelium and blockage of the vessels.

Structure
Thumb
Synonyms
  • Verteporfin
  • Verteporfina
  • Vertéporfine
  • Verteporfinum
External IDs
BPD / BPD-MA / CL 318952 / FF 18
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VisudyneInjection, powder, lyophilized, for solution2 mg/1mLIntravenousNovartis2000-04-142012-09-01Us
VisudynePowder, for solution15 mgIntravenousValeant Canada Lp Valeant Canada S.E.C.2000-06-26Not applicableCanada
VisudyneInjection, powder, lyophilized, for solution15 mg/1IntravenousValeant Pharmaceuticals North America2000-04-12Not applicableUs
VisudyneInjection, powder, lyophilized, for solution15 mg/1IntravenousQLT Ophthalmics, Inc.2000-04-12Not applicableUs
International/Other Brands
Visudine (Novartis)
Categories
UNII
0X9PA28K43
CAS number
129497-78-5
Weight
Average: 718.7942
Monoisotopic: 718.30026434
Chemical Formula
C41H42N4O8
InChI Key
YTZALCGQUPRCGW-MXVXOLGGSA-N
InChI
InChI=1S/C41H42N4O8/c1-9-23-20(2)29-17-34-27-13-10-26(39(49)52-7)38(40(50)53-8)41(27,5)35(45-34)19-30-22(4)25(12-15-37(48)51-6)33(44-30)18-32-24(11-14-36(46)47)21(3)28(43-32)16-31(23)42-29/h9-10,13,16-19,38,42,44H,1,11-12,14-15H2,2-8H3,(H,46,47)/b28-16-,29-17-,30-19-,31-16-,32-18-,33-18-,34-17-,35-19-/t38-,41+/m0/s1
IUPAC Name
3-[(23S,24R)-14-ethenyl-5-(3-methoxy-3-oxopropyl)-22,23-bis(methoxycarbonyl)-4,10,15,24-tetramethyl-25,26,27,28-tetraazahexacyclo[16.6.1.1³,⁶.1⁸,¹¹.1¹³,¹⁶.0¹⁹,²⁴]octacosa-1,3,5,7,9,11(27),12,14,16,18(25),19,21-dodecaen-9-yl]propanoic acid
SMILES
COC(=O)CCC1=C2NC(\C=C3/N=C(/C=C4\N\C(=C/C5=N/C(=C\2)/C(CCC(O)=O)=C5C)C(C=C)=C4C)C2=CC=C([C@@H](C(=O)OC)[C@@]32C)C(=O)OC)=C1C

Pharmacology

Indication

For the treatment of patients with predominantly classic subfoveal choroidal neovascularization due to age-related macular degeneration, pathologic myopia or presumed ocular histoplasmosis syndrome. Verteporfin can also be used to destroy tumors.

Associated Conditions
Pharmacodynamics

Verteporfin, otherwise known as benzoporphyrin derivative, is a medication used in conjunction with laser treatment to eliminate the abnormal blood vessels in the eye associated with conditions such as the wet form of macular degeneration. Verteporfin accumulates in these abnormal blood vessels and, when stimulated by nonthermal red light with a wavelength of 693 nm in the presence of oxygen, produces highly reactive short-lived singlet oxygen and other reactive oxygen radicals, resulting in local damage to the endothelium and blockage of the vessels.

Mechanism of action

Verteporfin is transported in the plasma primarily by lipoproteins. Once verteporfin is activated by light in the presence of oxygen, highly reactive, short-lived singlet oxygen and reactive oxygen radicals are generated. Light activation of verteporfin results in local damage to neovascular endothelium, resulting in vessel occlusion. Damaged endothelium is known to release procoagulant and vasoactive factors through the lipo-oxygenase (leukotriene) and cyclo-oxygenase (eicosanoids such as thromboxane) pathways, resulting in platelet aggregation, fibrin clot formation and vasoconstriction. Verteporfin appears to somewhat preferentially accumulate in neovasculature, including choroidal neovasculature. However, animal models indicate that the drug is also present in the retina. As singlet oxygen and reactive oxygen radicals are cytotoxic, Verteporfin can also be used to destroy tumor cells.

Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Metabolized to a small extent to its diacid metabolite by liver and plasma esterases. NADPH-dependent liver enzyme systems (including the cytochrome P450 isozymes) do not appear to play a role in the metabolism of verteporfin.

Route of elimination

Elimination is by the fecal route, with less than 0.01% of the dose recovered in urine.

Half life

Following intravenous infusion, verteporfin exhibits a bi-exponential elimination with a terminal elimination half-life of approximately 5-6 hours. Mild hepatic insufficiency increases half-life by approximately 20%.

Clearance
Not Available
Toxicity

Overdose of drug and/or light in the treated eye may result in nonperfusion of normal retinal vessels with the possibility of severe decrease in vision that could be permanent. An overdose of drug will also result in the prolongation of the period during which the patient remains photosensitive to bright light.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
ACETOPHENONEACETOPHENONE may increase the photosensitizing activities of Verteporfin.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Verteporfin.
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Verteporfin.
Aminolevulinic acidAminolevulinic acid may increase the photosensitizing activities of Verteporfin.
AncestimThe risk or severity of cytotoxicity can be increased when Ancestim is combined with Verteporfin.
BenzophenoneBenzophenone may increase the photosensitizing activities of Verteporfin.
BergaptenBergapten may increase the photosensitizing activities of Verteporfin.
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Verteporfin.
CarprofenCarprofen may increase the photosensitizing activities of Verteporfin.
CyamemazineCyamemazine may increase the photosensitizing activities of Verteporfin.
Food Interactions
Not Available

References

General References
  1. Chan WM, Lim TH, Pece A, Silva R, Yoshimura N: Verteporfin PDT for non-standard indications--a review of current literature. Graefes Arch Clin Exp Ophthalmol. 2010 May;248(5):613-26. doi: 10.1007/s00417-010-1307-z. Epub 2010 Feb 17. [PubMed:20162298]
  2. Nowak-Sliwinska P, Karocki A, Elas M, Pawlak A, Stochel G, Urbanska K: Verteporfin, photofrin II, and merocyanine 540 as PDT photosensitizers against melanoma cells. Biochem Biophys Res Commun. 2006 Oct 20;349(2):549-55. Epub 2006 Aug 22. [PubMed:16945338]
External Links
Human Metabolome Database
HMDB0014603
KEGG Drug
D01162
PubChem Compound
5362420
PubChem Substance
46506236
ChemSpider
4515032
ChEMBL
CHEMBL2052016
PharmGKB
PA451871
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Verteporfin
ATC Codes
S01LA01 — Verteporfin
AHFS Codes
  • 52:92.00 — EENT Drugs, Miscellaneous
FDA label
Download (39.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentMyopia1
1CompletedTreatmentVertebral Metastases1
1RecruitingTreatmentPleural Effusion, Malignant1
1RecruitingTreatmentRecurrent Prostate Cancer1
1Unknown StatusTreatmentBrain and Central Nervous System Tumors / Metastatic Cancers1
1, 2CompletedTreatmentChronic Central Serous Chorioretinopathy1
1, 2CompletedTreatmentMacular Degeneration / Subfoveal Choroidal Neovascularization1
1, 2CompletedTreatmentMelanoma (Skin)1
2CompletedTreatmentAge Related Macular Degeneration (ARMD)1
2CompletedTreatmentAge Related Macular Degeneration (ARMD) / Macular Edema (ME) / Subfoveal Choroidal Neovascularization1
2CompletedTreatmentAge-Related Macular Degeneration (ARMD)1
2CompletedTreatmentChronic Central Serous Chorioretinopathy1
2CompletedTreatmentMacular Degeneration1
2CompletedTreatmentMacular Degeneration / Subfoveal Choroidal Neovascularization2
2CompletedTreatmentNeovascular Age Related Macular Degeneration1
2RecruitingTreatmentMetastatic Breast Cancer (MBC)1
2Unknown StatusTreatmentPresumed Ocular Histoplasmosis (POHS)1
2WithdrawnTreatmentAge Related Macular Degeneration (ARMD)1
2, 3TerminatedTreatmentMacular Degeneration / Subfoveal Choroidal Neovascularization1
3CompletedTreatmentAge Related Macular Degeneration (ARMD)1
3CompletedTreatmentAge-Related Macular Degeneration (ARMD) / Subfoveal Choroidal Neovascularization1
3CompletedTreatmentMacular Degeneration2
3CompletedTreatmentMacular Degeneration / Subfoveal Choroidal Neovascularization2
3CompletedTreatmentMyopia / Subfoveal Choroidal Neovascularization1
3CompletedTreatmentVisual Impairment Due to Choroidal Neovascularization Secondary to Pathologic Myopia1
4CompletedTreatmentAge-Related Macular Degeneration (ARMD)2
4CompletedTreatmentMaculopathies, Age-Related / Subfoveal Choroidal Neovascularization1
4CompletedTreatmentPolypoidal Choroidal Vasculopathy (PCV)1
Not AvailableCompletedTreatmentCentral Serous Chorioretinopathy (CSC)1
Not AvailableCompletedTreatmentNeoplasms, Breast1
Not AvailableCompletedTreatmentPolypoidal Choroidal Vasculopathy (PCV)1
Not AvailableTerminatedPreventionMacular Degeneration / Retinal Detachment1
Not AvailableUnknown StatusTreatmentRetinal Vascular Disorders1
Not AvailableWithdrawnTreatmentNeovascular Age-Related Macular Degeneration1

Pharmacoeconomics

Manufacturers
  • Qlt inc
Packagers
  • Hollister-Stier Laboratories LLC
  • JHP Pharmaceuticals LLC
  • Novartis AG
  • QLT Inc.
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous15 mg/1
Injection, powder, lyophilized, for solutionIntravenous2 mg/1mL
Powder, for solutionIntravenous15 mg
Prices
Unit descriptionCostUnit
Visudyne 15 mg vial1702.64USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5214036No1993-05-252010-05-25Us
CA2536069No2008-06-032014-03-14Canada
CA1339927No1998-06-232015-06-23Canada
US5756541No1996-03-112016-03-11Us
US5798349No1995-08-252015-08-25Us
US5707608No1995-08-022015-08-02Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP2.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0136 mg/mLALOGPS
logP5.02ALOGPS
logP6.34ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)4.12ChemAxon
pKa (Strongest Basic)4.78ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area173.56 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity199.08 m3·mol-1ChemAxon
Polarizability81.29 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.5377
Blood Brain Barrier+0.6313
Caco-2 permeable-0.6425
P-glycoprotein substrateSubstrate0.7738
P-glycoprotein inhibitor INon-inhibitor0.577
P-glycoprotein inhibitor IINon-inhibitor0.5444
Renal organic cation transporterNon-inhibitor0.7681
CYP450 2C9 substrateNon-substrate0.8178
CYP450 2D6 substrateNon-substrate0.822
CYP450 3A4 substrateSubstrate0.6429
CYP450 1A2 substrateInhibitor0.7915
CYP450 2C9 inhibitorInhibitor0.7158
CYP450 2D6 inhibitorNon-inhibitor0.754
CYP450 2C19 inhibitorNon-inhibitor0.7057
CYP450 3A4 inhibitorNon-inhibitor0.5157
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.652
Ames testNon AMES toxic0.6596
CarcinogenicityNon-carcinogens0.9368
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6756 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9884
hERG inhibition (predictor II)Non-inhibitor0.9038
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Classification
Not classified

Drug created on June 13, 2005 07:24 / Updated on September 21, 2018 20:42