In vitro human skin concentrations following topical application of 2% tranexamic acid in co‐enhancer cream and branded cream formulations

Melasma is a common pigmentary disorder that responds well to treatment with oral and/or locally injected tranexamic acid but less so to topical application. We hypothesized that this may be due to an inability of some topical formulations of tranexamic acid to achieve robust therapeutic concentrations at the viable epidermal target site in the skin.To measure in vitro human epidermal and dermal skin concentrations of tranexamic acid following topical application of Fairence® T-Complex, co-enhancer cream and a Japanese branded cream control ("branded") and compare these with estimates of tranexamic acid potency obtained from in vivo human pharmacokinetic and clinical studies and in vitro pharmacodynamic studies on inhibition of fibrinolysis.Static vertical Franz cells and human abdominal skin were used to measure stratum corneum, viable epidermal, and dermal concentrations of tranexamic acid using HPLC-MS-MS analysis at 6 and 24 hour periods after topical application.Skin concentrations of tranexamic acid following application of the co-enhancer cream were robustly within the concentration range estimated to be required for efficacy at both 6 and 24 hours. Those from the branded cream control were within the lower range at 24 hours.These preclinical results support the benefits of conducting further studies, including a double-blind placebo-controlled clinical study, on Fairence® T-Complex, co-enhancer cream in patients with melasma. It is hypothesized that a more robust and timely clinical response may be achieved especially in refractory patients.