Pharmacokinetic-Pharmacodynamic Characterization of a Topical Photochemotherapy Using Brosimum gaudichaudii in C56BL/6 Mice

Photochemotherapy or ultraviolet radiating treatment is widely used in the treatment of vitiligo via oral dosages that often resulted in high systemic exposure and, consequently, frequent side effects. Given that vitiligo affects the skin, this work aimed to characterize the pharmacokinetic and pharmacodynamic properties of a topical gel formulation in order to optimize the amount of psoralen and 5-MOP in the viable epidermis and maximize the melanogenesis in vivo. A Box-Behnken factorial design was used to optimize the in vitro drug release, and the PK/PD of the optimized formulation were determined in C56BL/6 mouse. The formulation was optimized in 15% ethanol, 1.65% carboxymethyl cellulose, and 1.65% propylene glycol. A three-compartment model with linear elimination from the systemic compartment and a skin distribution factor to account for the difference between plasma and skin concentrations was fitted to the data from intravenous administration. The dermal model was best fitted with two-compartment model with elimination from the systemic compartment and dermal absorption from the skin. After an intravenous dose, the plasma exposure was 5-fold higher than that in the skin. After dermal application to the skin, the exposure for both drugs was 3.3-fold higher in the skin than in the plasma. The dermal bioavailability was 20% for 5-methoxypsoralen and 31% for psoralen. The extent of melanogenesis resulted from synthetic compounds, extract of Brosimum gaudichaudii Trecul, Moraceae, and this analyzed extracts plus long wave ultraviolet radiation were 14, 35, and 45%, respectively, indicating that the herbal extract is more effective than pure furanocumarins, and that long wave ultraviolet radiation can enhance melanogenesis effect of the extract.

Automated summary

The study optimized a topical gel formulation for the treatment of vitiligo, demonstrating good pharmacokinetic and pharmacodynamic properties in a mouse model.