Methyl aminolevulinate

Identification

Summary

Methyl aminolevulinate is a porphyrin precursor used to treat non-hyperkeratotic, non-pigmented actinic keratosis of the face and scalp.

Brand Names
Metvix, Metvixia
Generic Name
Methyl aminolevulinate
DrugBank Accession Number
DB00992
Background

Methyl aminolevulinate is a prodrug that is metabolised to Protoporphyrin IX (a photosensitizer) used in photodynamic therapy.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 145.1564
Monoisotopic: 145.073893223
Chemical Formula
C6H11NO3
Synonyms
  • 5-aminolevulinic acid methyl ester
  • Aminolevulinato de metilo
  • Aminolevulinic acid methyl ester
  • methyl 5-aminolevulinate
  • Methyl aminolevulinate
  • Methyl delta-aminolevulinate
  • methyl δ-aminolevulinate

Pharmacology

Indication

For topical use, in combination with 570 to 670 nm wavelength red light illumination, in the treatment of non-hyperkeratotic actinic keratoses of the face and scalp in immunocompetent patients when used in conjunction with lesion preparation (debridement using a sharp dermal curette).

Pharmacology
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Associated Conditions
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Contraindications
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Pharmacodynamics

After topical application of methyl aminolevulinate, porphyrins will accumulate intracellularly in the treated skin lesions. The intracellular porphyrins (including PpIX) are photoactive, fluorescing compounds and, upon light activation in the presence of oxygen, singlet oxygen is formed which causes damage to cellular compartments, in particular the mitochondria. Light activation of accumulated porphyrins leads to a photochemical reaction and thereby phototoxicity to the light-exposed target cells.

Mechanism of action

Photosensitization following application of methyl aminolevulinate cream occurs through the metabolic conversion of methyl aminolevulinate (prodrug) to photoactive porphyrins (PAP), which accumulates in the skin lesions to which the cream has been applied. When exposed to light of appropriate wavelength and energy, the accumulated photoactive porphyrins produce a photodynamic reaction, resulting in a cytotoxic process dependent upon the simultaneous presence of oxygen. The absorption of light results in an excited state of porphyrin molecules, and subsequent spin transfer from photoactive porphyrins to molecular oxygen generates singlet oxygen, which can further react to form superoxide and hydroxyl radicals.

Absorption

In vitro, after 24 hours the mean cumulative absorption through human skin was 0.26% of the administered dose.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

The severity of local phototoxic reactions such as erythema, pain and burning sensation may increase in case of prolonged application time or very high light intensity.

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
TretinoinThe risk or severity of adverse effects can be increased when Tretinoin is combined with Methyl aminolevulinate.
Interactions
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Methyl aminolevulinate hydrochloride7S73606O1A79416-27-6UJYSYPVQHFNBML-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
MetvixCream168 mg / gTopicalGalderma2009-06-16Not applicableCanada flag
MetvixiaCream168 mg/1gTopicalPenn Pharmaceutical Services Ltd.2007-10-02Not applicableUS flag
MetvixiaCream168 mg/1gTopicalGalderma2004-07-272012-11-29US flag

Categories

ATC Codes
L01XD03 — Methyl aminolevulinate
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 methyl esters / Methyl esters / Alpha-amino ketones / 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 acid methyl ester / Fatty acyl / Gamma-keto acid
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
delta-amino acid ester (CHEBI:724125)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
585NM85KYM
CAS number
33320-16-0
InChI Key
YUUAYBAIHCDHHD-UHFFFAOYSA-N
InChI
InChI=1S/C6H11NO3/c1-10-6(9)3-2-5(8)4-7/h2-4,7H2,1H3
IUPAC Name
methyl 5-amino-4-oxopentanoate
SMILES
COC(=O)CCC(=O)CN

References

General References
  1. Smits T, Moor AC: New aspects in photodynamic therapy of actinic keratoses. J Photochem Photobiol B. 2009 Sep 4;96(3):159-69. doi: 10.1016/j.jphotobiol.2009.06.003. Epub 2009 Jun 13. [Article]
Human Metabolome Database
HMDB0015127
KEGG Drug
D08204
PubChem Compound
157922
PubChem Substance
46507004
ChemSpider
138950
RxNav
337068
ChEBI
724125
ChEMBL
CHEMBL1096562
ZINC
ZINC000001909090
Therapeutic Targets Database
DAP001024
PharmGKB
PA164784028
Drugs.com
Drugs.com Drug Page
Wikipedia
Methyl_aminolevulinate
FDA label
Download (597 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedOtherActinic Keratosis (AK)1
4CompletedTreatmentActinic Keratosis (AK) / Natural Daylight Photodynamic Therapy1
4CompletedTreatmentMultiple Actinic Keratoses1
4RecruitingTreatmentSquamous Cell Carcinoma (SCC)1
4Unknown StatusTreatmentSuperficial Basal Cell Carcinoma1
3CompletedTreatmentActinic Keratosis (AK)5
3CompletedTreatmentCarcinoma, Basal Cell (BCC)1
3CompletedTreatmentSkin Aging1
2CompletedTreatmentAcne Vulgaris2
2CompletedTreatmentFacial Photodamage1

Pharmacoeconomics

Manufacturers
  • Galderma laboratories lp
Packagers
  • Galderma Laboratories
  • Penn Pharmaceutical Services Ltd.
Dosage Forms
FormRouteStrength
CreamTopical
CreamCutaneous160 MG/G
CreamTopical168 mg / g
CreamTopical16 % w/w
CreamTopical16 g
CreamTopical168 mg/1g
Prices
Unit descriptionCostUnit
Metvixia 16.8% cream82.2USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2215069No2006-09-122016-03-08Canada flag
US6034267No2000-03-072016-03-08US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityFreely solubleNot Available
logP-1.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility220.0 mg/mLALOGPS
logP-1.3ALOGPS
logP-0.85ChemAxon
logS0.18ALOGPS
pKa (Strongest Acidic)16.12ChemAxon
pKa (Strongest Basic)7.83ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area69.39 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity35.22 m3·mol-1ChemAxon
Polarizability14.55 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9652
Blood Brain Barrier+0.9677
Caco-2 permeable-0.5715
P-glycoprotein substrateNon-substrate0.6238
P-glycoprotein inhibitor INon-inhibitor0.806
P-glycoprotein inhibitor IINon-inhibitor0.7456
Renal organic cation transporterNon-inhibitor0.7855
CYP450 2C9 substrateNon-substrate0.8561
CYP450 2D6 substrateNon-substrate0.7888
CYP450 3A4 substrateNon-substrate0.6617
CYP450 1A2 substrateNon-inhibitor0.5854
CYP450 2C9 inhibitorNon-inhibitor0.9022
CYP450 2D6 inhibitorNon-inhibitor0.9309
CYP450 2C19 inhibitorNon-inhibitor0.8932
CYP450 3A4 inhibitorNon-inhibitor0.8724
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8936
Ames testNon AMES toxic0.8519
CarcinogenicityNon-carcinogens0.8042
BiodegradationReady biodegradable0.899
Rat acute toxicity1.7684 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8837
hERG inhibition (predictor II)Non-inhibitor0.8402
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

Drug created on June 13, 2005 13:24 / Updated on October 18, 2021 04:56