Hexaminolevulinate

Identification

Name
Hexaminolevulinate
Accession Number
DB06261
Type
Small Molecule
Groups
Approved
Description

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®.

Structure
Thumb
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
Product Ingredients
IngredientUNIICASInChI Key
Hexaminolevulinate hydrochlorideD4F329SL1O140898-91-5LZYXPFZBAZTOCH-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CysviewKit; Powder, for solution100 mgIntravesicalBiosyent Pharma Inc2015-12-14Not applicableCanada
CysviewKit100 mg/50mLPhotocure Inc2010-10-01Not applicableUs
CysviewKit100 mg/50mLGe Healthcare2010-09-012011-12-31Us
International/Other Brands
Hexvix (GE Healthcare)
Categories
UNII
G7H20TKI67
CAS number
140898-97-1
Weight
Average: 215.293
Monoisotopic: 215.15214354
Chemical Formula
C11H21NO3
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

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.

Associated Conditions
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
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.

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

Interactions

Drug Interactions
DrugInteraction
BCG vaccineBCG vaccine may decrease effectiveness of Hexaminolevulinate as a diagnostic agent.
Porfimer sodiumHexaminolevulinate may increase the photosensitizing activities of Porfimer sodium.
VerteporfinHexaminolevulinate may increase the photosensitizing activities of Verteporfin.
Food Interactions
Not Available

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. [PubMed:24248555]
  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. [PubMed:21068759]
  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. [PubMed:18177838]
External Links
KEGG Drug
D04436
PubChem Compound
6433083
PubChem Substance
310264865
ChemSpider
4938272
ChEBI
134892
ChEMBL
CHEMBL1201784
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cysview
AHFS Codes
  • 36:89.00* — Other Diagnostics
FDA label
Download (194 KB)
MSDS
Download (60.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailablePharmacokinetics1
1, 2CompletedDiagnosticColorectal Cancers1
1, 2CompletedTreatmentActinic Keratosis (AK)1
1, 2CompletedTreatmentCervical Dysplasia1
1, 2RecruitingTreatmentBasal Cell Carcinoma (BCC) / Neoplasms, Basal Cell / Photochemotherapy / Photosensitizing Agents1
1, 2TerminatedDiagnosticMalignant Neoplasm of Colon1
2TerminatedDiagnosticBladder Cancers1
2TerminatedTreatmentCervical Intraepithelial Neoplasia (CIN)1
2WithdrawnDiagnosticColorectal Cancers / Photodynamic Diagnosis1
2, 3Unknown StatusTreatmentGenital Erosive Lichen Planus1
3Active Not RecruitingTreatmentBladder Cancers / PDD / Recurrences1
3CompletedNot AvailableBladder Cancers1
3CompletedDiagnosticBladder Cancers3
4WithdrawnDiagnosticBladder Cancers1
Not AvailableCompletedNot AvailableBladder Cancers1
Not AvailableCompletedNot AvailablePhotodynamic Transurethral Resection of the Bladder (TUR-B)1
Not AvailableCompletedDevice FeasibilityBladder Cancers1
Not AvailableRecruitingNot AvailableBladder Cancers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Kit100 mg/50mL
Kit; powder, for solutionIntravesical100 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6034267No2000-03-072016-03-08Us
US7247655No2007-07-242016-03-08Us
US7530461No2009-05-122017-01-11Us
US7348361No2008-03-252020-11-06Us

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

Taxonomy

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
Delta amino acid or derivatives / Gamma-keto acid / Fatty acid ester / Keto acid / Fatty acyl / Alpha-aminoketone / Ketone / Carboxylic acid ester / Monocarboxylic acid or derivatives / Primary amine
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
Not Available

Drug created on March 19, 2008 10:19 / Updated on March 18, 2019 08:59