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Aminolevulinic acid | CAS No: 106-60-5 | GMP-certified suppliers
A medication that treats mild-to-moderate actinic keratosis via photodynamic therapy and aids glioma visualization during surgery, requiring high-purity, stable aminolevulinic acid API.
Therapeutic categories
Primary indications
- As a topical gel, aminolevulinic acid (ALA) is indicated for lesion-directed and field-directed treatment of actinic keratoses (AKs) of mild-to-moderate severity on the face and scalp in combination with photodynamic therapy (PDT) using BF-RhodoLED® lamp, a narrowband, red light illumination source
- As a topical solution, ALA can also be used for the same indication mentioned previously in addition to AKs of the upper extremities, but in conjunction with blue light illumination using the BLU-U Blue Light Photodynamic Therapy Illuminator
- Finally, ALA is also available as an oral solution to be used as an adjunct for the visualization of glioma during surgery
Product Snapshot
- Aminolevulinic acid is available in multiple formulation types including topical gels, solutions, patches, and oral solutions
- It is primarily utilized for photodynamic therapy in the treatment of actinic keratoses and as an adjunct for glioma visualization during surgery
- This API holds regulatory approval in key markets such as the United States, European Union, and Canada
Clinical Overview
ALA is administered topically as a gel or solution for lesion-directed and field-directed treatment of mild-to-moderate AK in combination with photodynamic therapy (PDT). Specific illumination devices approved for use include the BF-RhodoLED® lamp, which emits narrowband red light, and the BLU-U Blue Light Photodynamic Therapy Illuminator for blue light exposure. ALA is also formulated as an oral solution utilized as an adjunctive agent during glioma surgery to enhance tumor visualization.
Pharmacodynamically, ALA is not a photosensitizer itself but is metabolized intracellularly to protoporphyrin IX (PpIX), a potent photosensitizing agent. Under physiologic conditions, endogenous ALA synthesis is tightly regulated via feedback inhibition of ALA synthetase by intracellular heme. Exogenous administration bypasses this control, leading to accumulation of PpIX in target tissues. Upon exposure to appropriate wavelengths of light and in the presence of oxygen, PpIX enters an excited state and generates reactive oxygen species such as singlet oxygen, superoxide, and hydroxyl radicals. This photodynamic reaction induces localized cytotoxicity, selectively targeting dysplastic or neoplastic cells.
Key absorption, distribution, metabolism, and excretion (ADME) parameters have not been extensively characterized in the context of topical or oral formulations due to its rapid intracellular metabolism and localized mechanism of action. Safety considerations include local skin reactions such as erythema, edema, and photosensitivity; systemic toxicity is limited by the localized use of ALA and rapid metabolic clearance. There are no major systemic contraindications reported, but caution with light exposure post-application is necessary.
Notable approved formulations include topical gels and solutions marketed under various proprietary names in the context of photodynamic therapy for AK, as well as oral solutions for intraoperative fluorescence-guided glioma resection.
From an API sourcing perspective, aminolevulinic acid requires stringent quality controls to ensure chemical purity, stability, and consistent bioavailability. Manufacturers should comply with pharmacopeial standards and GMP regulations. The inherent instability of ALA necessitates appropriate handling and storage conditions to prevent degradation, which can affect clinical efficacy and safety profiles. Reliable traceability and documentation are essential for regulatory submissions and quality assurance in pharmaceutical manufacturing.
Identification & chemistry
| Generic name | Aminolevulinic acid |
|---|---|
| Molecule type | Small molecule |
| CAS | 106-60-5 |
| UNII | 88755TAZ87 |
| DrugBank ID | DB00855 |
Pharmacology
| Summary | Aminolevulinic acid (ALA) acts as a metabolic precursor that is converted intracellularly to protoporphyrin IX (PpIX), a photosensitizer that accumulates selectively in target tissues. Upon activation by specific wavelengths of light, PpIX induces a photodynamic reaction producing reactive oxygen species that mediate cytotoxic effects. This mechanism underlies ALA’s use in photodynamic therapy for treating actinic keratoses and as an intraoperative adjunct for glioma visualization. |
|---|---|
| Mechanism of action | According to the presumed mechanism of action, photosensitization following application of aminolevulinic acid (ALA) topical solution occurs through the metabolic conversion of ALA to protoporphyrin IX (PpIX), which accumulates in the skin to which aminolevulinic acid has been applied. When exposed to light of appropriate wavelength and energy, the accumulated PpIX produces a photodynamic reaction, a cytotoxic process dependent upon the simultaneous presence of light and oxygen. The absorption of light results in an excited state of the porphyrin molecule, and subsequent spin transfer from PpIX to molecular oxygen generates singlet oxygen, which can further react to form superoxide and hydroxyl radicals. Photosensitization of actinic (solar) keratosis lesions using aminolevulinic acid, plus illumination with the BLU-UTM Blue Light Photodynamic Therapy Illuminator (BLU-U), is the basis for aminolevulinic acid photodynamic therapy (PDT). |
| Pharmacodynamics | The metabolism of aminolevulinic acid (ALA) is the first step in the biochemical pathway resulting in heme synthesis. Aminolevulinic acid is not a photosensitizer, but rather a metabolic precursor of protoporphyrin IX (PpIX), which is a photosensitizer. The synthesis of ALA is normally tightly controlled by feedback inhibition of the enzyme, ALA synthetase, presumably by intracellular heme levels. ALA, when provided to the cell, bypasses this control point and results in the accumulation of PpIX, which is converted into heme by ferrochelatase through the addition of iron to the PpIX nucleus. |
Targets
| Target | Organism | Actions |
|---|---|---|
| Delta-aminolevulinic acid dehydratase | Humans | inducer |
ADME / PK
| Absorption | Oral bioavailability is 50-60%. ### **Topical gel** Pharmacokinetics (PK) of aminolevulinic acid (ALA) and PpIX was evaluated in a trial of 12 adult subjects with mild to moderate AK with at least 10 AK lesions on the face or forehead. A single dose of one entire tube of ALA (2 grams) was applied under occlusion for 3 hours followed by photodynamic therapy (PDT) to a total area of 20 cm<sup>2</sup>. The mean ± SD baseline plasma ALA and PpIX concentrations were 20.16 ± 16.53 ng/mL and 3.27 ± 2.40 ng/mL, respectively. In most subjects, an up to 2.5-fold increase of ALA plasma concentrations was observed during the first 3 hours after ALA application. The mean ± SD area under the concentration time curve (AUC<sub>0-t</sub>) and maximum concentration (C<sub>max</sub>) for baseline corrected ALA (n=12) were 142.83 ± 75.50 ng.h/mL and 27.19 ± 20.02 ng/mL, respectively. The median T<sub>max</sub> (time at which C<sub>max</sub> occurred) was 3 hours. ### **Topical solution** Two human pharmacokinetic (PK) studies were conducted in subjects with minimally to moderately thick actinic keratoses on the upper extremities, having at least 6 lesions on one upper extremity and at least 12 lesions on the other upper extremity. A single dose comprising of two topical applications of ALA topical solution (each containing 354 mg ALA HCl) were directly applied to the lesions and occluded for 3 hours prior to light treatment. The first PK study was conducted in 29 subjects and PK parameters of ALA were assessed. The baseline corrected mean ± SD of the maximum concentration (C<sub>max</sub>) of ALA was 249.9 ± 694.5 ng/mL and the median T<sub>max</sub> was 2 hours post dose. The mean ± SD exposure to ALA, as expressed by area under the concentration time curve (AUC<sub>t</sub>) was 669.9 ± 1610 ng·hr/mL. The mean ± SD elimination half-life (t<sub>1/2</sub>) of ALA was 5.7 ± 3.9 hours. A second PK study was conducted in 14 subjects and PK parameters of ALA and PpIX were measured. The baseline corrected PpIX concentrations were negative in at least 50% of samples in 50% (7/14) subjects and AUC could not be estimated reliably. The baseline-corrected mean ± SD of C<sub>max</sub> for ALA and PpIX was 95.6 ± 120.6 ng/mL and 0.95 ± 0.71 ng/mL, respectively. The median T<sub>max</sub> of ALA and PpIX was 2 hours post dose and 12 hours post dose, respectively. The mean AUCt of ALA was 261.1 ± 229.3 ng·hr/mL. The mean ± SD t<sub>1/2</sub> of ALA was 8.5 ± 6.7 hours. ### **Oral solution** In 12 healthy subjects, the absolute bioavailability of ALA following the recommended dose of ALA solution was 100.0% + 1.1 with a range of 78.5% to 131.2%. Maximum ALA plasma concentrations were reached with a median of 0.8 hour (range 0.5 – 1.0 hour). |
|---|---|
| Half-life | The mean ± SD elimination half-life (t<sub>1/2</sub>) of aminolevulinic acid was 5.7 ± 3.9 hours for the topical solution formulation and the mean half-life was 0.9 ± 1.2 hours for the oral solution formulation. In another pharmacokinetic studies with 6 healthy volunteers using a 128 mg dose, the mean half-life was 0.70 ± 0.18 h after the oral dose and 0.83 ± 0.05 h after the intravenous dose. |
| Protein binding | In in vitro experiments using aminolevulinic acid (ALA) concentrations up to approximately 25% of the maximal concentration that occurs in plasma following the recommended dose of ALA solution, the mean protein binding of ALA was 12%. |
| Metabolism | Exogenous aminolevulinic acid (ALA) is metabolized to PpIX, but the fraction of administered ALA that is metabolized to PpIX is unknown. The average plasma AUC of PpIX is less than 6% of that of ALA. |
| Route of elimination | In 12 healthy subjects, excretion of parent aminolevulinic acid (ALA) in urine in the 12 hours following administration of the recommended dose of ALA solution was 34 + 8% (mean + std dev) with a range of 27% to 57%. |
| Volume of distribution | In healthy volunteers, the administration of aminolevulinic acid resulted in a volume of distribution of 9.3 ± 2.8 L intravenously and 14.5 ± 2.5 orally.[11961050] |
Formulation & handling
- Aminolevulinic acid is a small molecule suitable for topical, cutaneous, and oral formulations, with common forms including gels, patches, and powders for solution.
- High water solubility and low LogP suggest good aqueous formulation compatibility but potential challenges in skin permeation enhancement.
- Handling should consider its solid state and sensitivity to light and moisture to maintain stability during storage and compounding.
Regulatory status
| Lifecycle | The active pharmaceutical ingredient is in the mature phase of its lifecycle, with key patents having expired between 2009 and 2019 in the United States, and established presence in the US, EU, and Canadian markets. |
|---|
| Markets | US, EU, Canada |
|---|
Supply Chain
| Supply chain summary | Aminolevulinic acid is primarily manufactured and packaged by a single originator company with branded products distributed across the US, EU, and Canadian markets. Multiple patents granted between 2009 and 2019 indicate extended intellectual property protection, though some earlier patents have likely expired, potentially allowing for existing or upcoming generic competition. |
|---|
Safety
| Toxicity | There are no available human data on aminolevulinic acid (ALA) in pregnant women to inform a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, no adverse developmental effects were observed with oral ALA HCl administration to pregnant rabbits during organogenesis at doses 3 times the maximum recommended human oral dose. No carcinogenicity testing has been carried out using ALA. No evidence of mutagenic effects was seen in four studies conducted with ALA to evaluate this potential. In the Salmonella-Escherichia coli/mammalian microsome reverse mutation assay (Ames mutagenicity assay), no increases in the number of revertants were observed with any of the tester strains. In the Salmonella-Escherichia coli/mammalian microsome reverse mutation assay in the presence of solar light radiation (Ames mutagenicity assay with light), ALA did not cause an increase in the number of revertants per plate of any of the tester strains in the presence or absence of simulated solar light. In the L5178Y TK± mouse lymphoma forward mutation assay, ALA was evaluated as negative with and without metabolic activation under the study conditions. PpIX formation was not demonstrated in any of these in vitro studies. In the in vivo mouse micronucleus assay, ALA was considered negative under the study exposure conditions. In contrast, at least one report in the literature has noted genotoxic effects in cultured rat hepatocytes after ALA exposure with PpIX formation. Other studies have documented oxidative DNA damage in vivo and in vitro as a result of ALA exposure. No assessment of effects of ALA HCl on fertility has been performed in laboratory animals. It is unknown what effects systemic exposure to ALA HCl might have on fertility or reproductive function. |
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- Aminolevulinic acid (ALA) has demonstrated no mutagenic effects in standard in vitro and in vivo assays, though isolated reports indicate potential oxidative DNA damage under certain conditions
- Carcinogenicity studies have not been conducted for ALA
- Reproductive toxicity data are limited
Aminolevulinic acid is a type of Sensitizers in photodynamic and radiotherapy
Sensitizers play a crucial role in the fields of photodynamic therapy (PDT) and radiotherapy. These pharmaceutical active pharmaceutical ingredients (APIs) are designed to enhance the efficacy of these treatment modalities by sensitizing targeted tissues to the therapeutic effects of light or radiation.
In photodynamic therapy, sensitizers are employed to selectively accumulate within cancer cells. These compounds possess unique properties that allow them to absorb specific wavelengths of light, which triggers a photochemical reaction, resulting in the generation of reactive oxygen species (ROS). The ROS, in turn, cause oxidative damage to the cancer cells, ultimately leading to their destruction. Sensitizers are carefully chosen based on their absorption spectra, photostability, and targeting capabilities to maximize treatment outcomes.
Similarly, in radiotherapy, sensitizers are utilized to sensitize cancer cells to ionizing radiation. These sensitizers enhance the effects of radiation by increasing the production of free radicals and promoting DNA damage within tumor cells. This amplifies the cytotoxic effects of radiation, leading to improved tumor control and potentially reducing the dosage required for treatment.
Research and development in the field of sensitizers for PDT and radiotherapy are focused on discovering novel compounds with optimized properties, such as enhanced absorption, improved selectivity, and reduced side effects. Furthermore, efforts are underway to develop multifunctional sensitizers that can combine photodynamic and radiotherapeutic properties, offering a synergistic approach for cancer treatment.
In conclusion, sensitizers form a critical subcategory of pharmaceutical APIs in the context of photodynamic and radiotherapy. They enhance the therapeutic effects of light and radiation by sensitizing cancer cells, thereby improving treatment outcomes in the fight against cancer.
Aminolevulinic acid (Sensitizers in photodynamic and radiotherapy), classified under Anticancer drugs
Anticancer drugs belong to the pharmaceutical API (Active Pharmaceutical Ingredient) category designed specifically to combat cancer cells. These powerful medications play a crucial role in cancer treatment and are developed to target and destroy cancerous cells, preventing their growth and spread.
Anticancer drugs are classified based on their mode of action and can include various types such as chemotherapy drugs, targeted therapy drugs, immunotherapy drugs, and hormonal therapy drugs. Chemotherapy drugs work by interfering with the cell division process, thereby inhibiting the growth of cancer cells. Targeted therapy drugs, on the other hand, are designed to attack specific molecules or genes involved in cancer growth, minimizing damage to healthy cells. Immunotherapy drugs stimulate the body's immune system to recognize and destroy cancer cells. Hormonal therapy drugs are used in cancers that are hormone-dependent, such as breast or prostate cancer, to block the hormones that fuel cancer cell growth.
These APIs are typically synthesized through complex chemical processes in state-of-the-art manufacturing facilities. Stringent quality control measures ensure the purity, potency, and safety of these drugs. Anticancer APIs undergo rigorous testing and adhere to stringent regulatory guidelines before being approved for clinical use.
Due to their critical role in cancer treatment, anticancer drugs are in high demand worldwide. Researchers and pharmaceutical companies continually strive to develop new and more effective APIs in this category to enhance treatment outcomes and minimize side effects. The ongoing advancements in the field of anticancer drug development offer hope for improved cancer therapies and better patient outcomes.
Aminolevulinic acid API manufacturers & distributors
Compare qualified Aminolevulinic acid API suppliers worldwide. We currently have 4 companies offering Aminolevulinic acid API, with manufacturing taking place in 3 different countries. Use the table below to review supplier type, countries of origin, certifications, product portfolio and GMP audit availability.
| Supplier | Type | Country | Product origin | Certifications | Portfolio |
|---|---|---|---|---|---|
| Caesar & Loretz GmbH (CAE... | Distributor | Germany | Germany | BSE/TSE, CoA, GMP, ISO9001, MSDS | 211 products |
| Cambrex, Karlskoga | Producer | Sweden | Sweden | CoA, USDMF | 8 products |
| Heraeus | Producer | Germany | Germany | CoA, USDMF | 10 products |
| Midas Pharma | Producer | Germany | Unknown | CoA, USDMF | 6 products |
When sending a request, specify which Aminolevulinic acid API quality you need: for example EP (Ph. Eur.), USP, JP, BP, or another pharmacopoeial standard, as well as the required grade (base, salt, micronised, specific purity, etc.).
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