The Safety and Tolerability of Topically Delivered Kynurenic Acid in Humans. A Phase 1 Randomized Double-Blind Clinical Trial

J Pharm Sci. 2018 Jun;107(6):1572-1576. doi: 10.1016/j.xphs.2018.01.023. Epub 2018 Feb 6.


Scarring is a consequence of biological tissue repair following trauma. Currently, there are no generally agreed ways to prevent scarring. Recently, kynurenic acid has shown to be a potent modulator of extracellular matrix deposition and remodeling. Kynurenic acid can reduce matrix deposition and other fundamental characteristics of fibrosis in vitro and in vivo. Specifically, kynurenic acid has shown to increase matrix metalloproteinase-1 activity and subsequently reduce collagen deposition in a rabbit ear scar model. In the present study kynurenic acid cream in different concentrations was topically applied on healthy skin on volunteers to assess skin reactions and skin sensitivity in both acute and chronic application settings. Skin reactions were assessed, and concentrations for kynurenic acid were assessed both form serum and urine. Results showed to acute or delayed skin reactions. Kynurenic acid was not detectable in blood at any time point, and only trace elements of kynurenic acid were found in urine. This study supports safety and tolerability of topically administered FS2 when using a liposomal, compounding base carrier.

Keywords: HPLC; formulation; liposomes; natural products; skin.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Adolescent
  • Adult
  • Aged
  • Double-Blind Method
  • Excitatory Amino Acid Antagonists / administration & dosage*
  • Excitatory Amino Acid Antagonists / adverse effects
  • Excitatory Amino Acid Antagonists / blood
  • Excitatory Amino Acid Antagonists / urine
  • Humans
  • Kynurenic Acid / administration & dosage*
  • Kynurenic Acid / adverse effects
  • Kynurenic Acid / blood
  • Kynurenic Acid / urine
  • Liposomes / adverse effects
  • Liposomes / chemistry
  • Middle Aged
  • Skin / drug effects*
  • Skin / pathology
  • Skin Cream / adverse effects
  • Skin Cream / chemistry
  • Skin Diseases / chemically induced
  • Skin Diseases / diagnosis
  • Skin Tests
  • Young Adult


  • Excitatory Amino Acid Antagonists
  • Liposomes
  • Kynurenic Acid

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