Methyl aminolevulinate

Methyl aminolevulinate with red light in AK, BCC and Bowen’s disease

After topical application of methyl aminolevulinate, porphyrins 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.

Methyl aminolevulinate with daylight in AK

After topical application of methyl aminolevulinate, porphyrins are produced intracellularly in the treated skin lesions. The intracellular porphyrins (including PpIX) are photoactive, fluorescing compounds and, upon daylight activation in the presence of oxygen, singlet oxygen is formed which causes damage to cellular compartments, in particular the mitochondria. When methyl aminolevulinate is used with daylight, PpIX is continuously being produced and activated within the target cells during the 2 hours of daylight exposure creating a constant micro-phototoxic effect. Daylight may not be sufficient for methyl aminolevulinate daylight treatment during winter months in certain parts of Europe. Methyl aminolevulinate daylight photodynamic therapy is feasible all year long in southern Europe, from February to October in middle Europe, and from March to October in northern Europe.

In vitro dermal absorption of radiolabelled methyl aminolevulinate applied to human skin has been studied. After 24 hours the mean cumulative absorption through human skin was 0.26% of the administered dose. A skin depot containing 4.9% of the dose was formed. No corresponding studies in human skin with damage similar to actinic keratosis lesions and additionally roughened surface or without stratum corneum were performed.

In humans, a higher degree of accumulation of porphyrins in lesions compared to normal skin has been demonstrated with methyl aminolevulinate cream. After application of the cream for 3 hours and subsequent illumination with non-coherent light of 570–670 nm wavelength and a total light dose of 75 J/cm², complete photobleaching occurs with levels of porphyrins returning to pre-treatment values.

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity. When methyl aminolevulinate was administered by IV at high dose levels during gestation, studies in animals showed reproductive toxicity. Findings included effects on ossification in rabbits and a slightly longer gestation duration in rats. As a result, methyl aminolevulinate should be avoided during pregnancy in humans.

Carcinogenicity studies have not been performed with methyl aminolevulinate.