Azelaic acid-pharmacology, toxicology and mechanisms of action on keratinization in vitro and in vivo

Azelaic acid (AZA) is an endogenous C9-dicarboxylic acid synthesized by omega-oxidation from fatty acids and found as a physiological component in human urine. After topical application, about 3.6% is absorbed through the skin. AZA is metabolized via the β-oxidation pathway ending in the formation of malonyl-CoA or acetyl-CoA. The substance shows in vitro and in vivo effects on at least two major factors in the pathogenesis of acne. It leads to normalization of the disturbed terminal differentiation of keratinocytes in the follicular infundibulum and has a strong antimicrobial action. Intra-and interfollicular hyperkeratosis is found to be significantly reduced or normalized after 8–12 weeks of twice daily treatment of acneic skin with 20% AZA cream. The keratohyalin granules decrease in number and size in both follicular and epidermal keratinocytes. Animal experiments have revealed no mutagenic or relevant toxic side-effects after acute and chronic exposure. In addition, in vitro data suggest that AZA exerts anti-inflammatory effects by decreasing the release of reactive oxygen species from neutrophils.