Pharmacology

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.

According to the presumed mechanism of action, photosensitization following application of LEVULAN KERASTICK Topical Solution occurs through the metabolic conversion of ALA to PpIX, which accumulates in the skin to which LEVULAN Topical Solution 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 the LEVULAN KERASTICK, plus illumination with the BLU-U® Blue Light Photodynamic Therapy Illuminator (BLU-U), is the basis for LEVULAN photodynamic therapy (PDT).