Hexaminolevulinate

Identification

Summary

Hexaminolevulinate is an optical imaging agent used to perform Blue Light Cystoscopy (BLC™) in order to detect carcinoma of the bladder.

Brand Names
Cysview
Generic Name
Hexaminolevulinate
DrugBank Accession Number
DB06261
Background

Hexaminolevulinate is an optical imaging drug. In solution form it is instilled intravesically for use with photodynamic blue light cystoscopy as an adjunct to white light cystoscopy. On May 28, 2010, the U.S. Food and Drug Administration (FDA) granted approval for hexaminolevulinate hydrochloride (Cysview for Intravesical Solution, Photocure ASA), as an optical imaging agent for use in combination with the Karl Storz Photodynamic Diagnostic D-Light C (PDD) System for cystoscopic detection of non-muscle invasive papillary cancer of the bladder for patients suspected or known to have lesion(s) on the basis of a prior cystoscopy. Hexaminolevulinate is manufactured under the brand Cysview® by Photocure ASA. In Europe, Hexaminolevulinate is marketed under the brand Hexvix®.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 215.293
Monoisotopic: 215.15214354
Chemical Formula
C11H21NO3
Synonyms
  • 4-Hexyloxycarbonyl-2-oxobutylammoniumchloride
  • Hexaminolevulinato
  • Hexyl 5-amino-4-oxopentanoate hydrochloride
  • Hexyl(5-amino-4-oxopentanoat)-hydrochlorid
  • Pentanoic acid, 5-amino-4-oxo-, hexyl ester, hydrochloride
External IDs
  • P-1026

Pharmacology

Indication

Hexaminolevulinate is indicated for use in the cystoscopic detection of non-muscle invasive papillary cancer of the bladder among patients suspected or known to have lesion(s) on the basis of a prior cystoscopy.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

In vitro studies have shown increased porphyrin fluorescence in normal urothelium after exposure to hexaminolevulinate hydrochloride intravesical solution. In the human bladder, a greater accumulation of porphyrins is proposed in neoplastic or inflamed cells, compared to normal urothelium. After bladder instillation of hexaminolevulinate hydrochloride intravesical solution for approximately 1 hour and subsequent illumination with blue light at wavelengths 360 – 450nm, the porphyrins will fluoresce red.

Mechanism of action

Hexaminolevulinate is an ester of the heme precursor, aminolevulinic acid. After bladder instillation, hexaminolevulinate enters the bladder mucosa and is proposed to enter the intracellular space of mucosal cells where it is used as a precursor in the formation of the photoactive intermediate protoporphyrin IX (PpIX) and other photoactive porphyrins (PAPs). PpIX and PAPs are reported to accumulate preferentially in neoplastic cells as compared to normal urothelium, partly due to altered enzymatic activity in the neoplastic cells. After excitation with light at wavelengths between 360 and 450 nm, PpIX and other PAPs return to a lower energy level by fluorescing, which can be detected and used for cystoscopic detection of lesions. The fluorescence from tumor tissue appears bright red and demarcated, whereas the background normal tissue appears dark blue. Similar processes may occur in inflamed cells.

Absorption

Absolute bioavailability 7% (90% confidence interval [CI]: 5%-10%)

Volume of distribution

Not Available

Protein binding

No evidence of significant binding.

Metabolism

Rapid metabolism in human blood.

Route of elimination

Not Available

Half-life

Biphasic elimination, with an initial elimination half-life of 39 minutes, followed by a terminal half-life of approximately 76 hours.

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

No studies in animals have been conducted to evaluate the carcinogenic potential of hexaminolevulinate hydrochloride.

Hexaminolevulinate hydrochloride was not mutagenic in in-vitro reverse mutation tests in bacteria, or in chromosome aberration tests in human peripheral blood lymphocytes, and was negative in an in-vivo micronucleus test in mice after intravenous injection of doses up to 45 mg/kg in the absence of light activation.

Adequate studies have not been performed to evaluate the genetic toxicity of hexaminolevulinate hydrochloride in the presence of light activation.

Adequate reproductive and developmental toxicity studies in animals have not been performed to evaluate the effects of hexaminolevulinate hydrochloride on fertility.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
BCG vaccineBCG vaccine may decrease effectiveness of Hexaminolevulinate as a diagnostic agent.
Porfimer sodiumHexaminolevulinate may increase the photosensitizing activities of Porfimer sodium.
TretinoinThe risk or severity of adverse effects can be increased when Tretinoin is combined with Hexaminolevulinate.
VerteporfinHexaminolevulinate may increase the photosensitizing activities of Verteporfin.
Interactions
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Hexaminolevulinate hydrochlorideD4F329SL1O140898-91-5LZYXPFZBAZTOCH-UHFFFAOYSA-N
International/Other Brands
Hexvix (GE Healthcare)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CysviewKit100 mg/50mLIntravesicalGe Healthcare2010-09-012011-12-31US flag
CysviewKit; Powder, for solution100 mg / vialIntravesicalBiosyent Pharma Inc2015-12-14Not applicableCanada flag
CysviewKit100 mg/50mLIntravesicalPhotocure Inc.2018-05-01Not applicableUS flag

Categories

ATC Codes
V04CX06 — Hexaminolevulinate
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as delta amino acids and derivatives. These are compounds containing a carboxylic acid group and an amino group at the C5 carbon atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Delta amino acids and derivatives
Alternative Parents
Gamma-keto acids and derivatives / Fatty acid esters / Alpha-amino ketones / Carboxylic acid esters / Monocarboxylic acids and derivatives / Organopnictogen compounds / Organic oxides / Monoalkylamines / Hydrocarbon derivatives
Substituents
Aliphatic acyclic compound / Alpha-aminoketone / Amine / Carbonyl group / Carboxylic acid ester / Delta amino acid or derivatives / Fatty acid ester / Fatty acyl / Gamma-keto acid / Hydrocarbon derivative
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
G7H20TKI67
CAS number
140898-97-1
InChI Key
RYQOILLJDKPETL-UHFFFAOYSA-N
InChI
InChI=1S/C11H21NO3/c1-2-3-4-5-8-15-11(14)7-6-10(13)9-12/h2-9,12H2,1H3
IUPAC Name
hexyl 5-amino-4-oxopentanoate
SMILES
[H]N([H])CC(=O)CCC(=O)OCCCCCC

References

General References
  1. Yang LP: Hexaminolevulinate blue light cystoscopy: a review of its use in the diagnosis of bladder cancer. Mol Diagn Ther. 2014 Feb;18(1):105-16. doi: 10.1007/s40291-013-0068-x. [Article]
  2. O'Brien T, Thomas K: Bladder cancer: Photodynamic diagnosis can improve surgical outcome. Nat Rev Urol. 2010 Nov;7(11):598-9. doi: 10.1038/nrurol.2010.183. [Article]
  3. Hillemanns P, Wang X, Hertel H, Andikyan V, Hillemanns M, Stepp H, Soergel P: Pharmacokinetics and selectivity of porphyrin synthesis after topical application of hexaminolevulinate in patients with cervical intraepithelial neoplasia. Am J Obstet Gynecol. 2008 Mar;198(3):300.e1-7. doi: 10.1016/j.ajog.2007.07.045. Epub 2008 Feb 21. [Article]
KEGG Drug
D04436
PubChem Compound
6433083
PubChem Substance
310264865
ChemSpider
4938272
RxNav
1426872
ChEBI
134892
ChEMBL
CHEMBL1201784
ZINC
ZINC000001554392
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cysview
FDA label
Download (194 KB)
MSDS
Download (60.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4WithdrawnDiagnosticBladder Cancer, Cancer1
3CompletedNot AvailableBladder Cancer, Cancer1
3CompletedDiagnosticBladder Cancer, Cancer3
3CompletedTreatmentBladder Cancer, Cancer / PDD / Recurrences1
2TerminatedDiagnosticBladder Cancer, Cancer1
2TerminatedTreatmentCervical Intraepithelial Neoplasia (CIN)1
2WithdrawnDiagnosticColorectal Carcinoma (CRC) / Photodynamic Diagnosis1
2, 3CompletedTreatmentGenital Lichen Planus1
1CompletedNot AvailablePharmacokinetics1
1, 2Active Not RecruitingTreatmentCarcinoma, Basal Cell (BCC) / Neoplasms, Basal Cell / Photochemotherapy / Photosensitizing Agents1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
KitIntravesical100 mg/50mL
Kit; powder, for solutionIntravesical100 mg / vial
Powder, for solutionIntravenous; Intravesical85 MG
Powder, for solutionIntravesical85 MG
SolutionIntravesical85 MG
Injection, powder, for solutionIntravesical
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6034267No2000-03-072016-03-08US flag
US7247655No2007-07-242016-03-08US flag
US7530461No2009-05-122017-01-11US flag
US7348361No2008-03-252020-11-06US flag
US10556010No2020-02-112036-12-19US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.511 mg/mLALOGPS
logP1.55ALOGPS
logP1.37ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)16.11ChemAxon
pKa (Strongest Basic)7.83ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area69.39 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity58.29 m3·mol-1ChemAxon
Polarizability24.96 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

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

Drug created on March 19, 2008 16:19 / Updated on October 16, 2021 12:31