The Efficacy and Safety of 4-n-butylresorcinol 0.1% Cream for the Treatment of Melasma: A Randomized Controlled Split-face Trial

Abstract

Background: Melasma is a common acquired symmetrical hypermelanosis that occurs on sun-exposed areas, and it is frequently observed among women. Various treatment modalities have been tried, but none are completely satisfactory. 4-n-butylresorcinol, which is a resorcinol derivative that has an inhibitory effect on both tyrosinase and tyrosinase-related protein-1, was introduced in 1995 and it has received increasing attention as a new hypopigmenting agent. However, the hypopigmenting effect of 4-n-butylresorcinol in human subjects has only been shown in a few studies. Objective: The aim of this study was to investigate the hypopigmenting efficacy and safety of 4-n-butylresorcinol 0.1% cream for the treatment of melasma. Methods: Twenty patients with melasma were enrolled to this randomized, double-blind, vehicle-controlled, split-face comparative study. The patients were instructed to apply 4-n-butylresorcinol 0.1% cream or vehicle to each side of the face twice daily for 8 weeks. Mexameter measurements were performed along with photography at baseline, 4 weeks and 8 weeks. Adverse events were observed and recorded throughout the study. Results: All the patients completed the study. Mexameter measurements demonstrated that the melanin index of the treated side showed a significant decrease when compared with that of the vehicle-treated side after 4 weeks (p=0.006) and after 8 weeks (p＜0.0005). All the adverse reactions were mild and transient. Conclusion: 4-n-butylresorcinol 0.1% cream showed rapid efficacy and it was well tolerated when used for the treatment of melasma.

Efficacy of liposome‐encapsulated 4‐n‐butylresorcinol and resveratrol cream in the treatment of melasma

“…In a randomized, double-blind, vehicle-controlled, split-face study, the use of 0.1% 4nBR cream significantly reduced lesional MI compared with control at week 4 and week 8. 6 Lesional MI decreased by −3.43% at week 4 and −4.87% at week 8 from the baseline. Mild irritation was observed in 10% of the patients at week 4 and self-limited at week 8.…”

“…In a series of clinical trials, we have reported clinical efficacy and safety of 0.1% 4nBR cream in the treatment of melasma. In a randomized, double‐blind, vehicle‐controlled, split‐face study, the use of 0.1% 4nBR cream significantly reduced lesional MI compared with control at week 4 and week 8 . Lesional MI decreased by −3.43% at week 4 and −4.87% at week 8 from the baseline.…”

“…The synergistic action of 4nBR and RSV may also contribute to the rapid occurrence of depigmentation clinically as early as 2 weeks. Several depigmenting products including 0.1% 4nBR cream exert its maximal potency after the use of more than 4 weeks . Rapid onset of depigmenting effect is as important as its potency in a clinical setting because it affects patient's adherence to the product.…”

“…4‐n‐butylresorcinol (4nBR) is a potent depigmenting agent which directly inhibits tyrosinase activity . We previously reported the efficacy of 0.1% 4nBR cream with or without liposomal encapsulation in the treatment melasma in a series of randomized, double‐blind, vehicle‐controlled, split‐face studies . Resveratrol (RSV) not only binds to tyrosinase directly but also regulates various melanogenic signaling molecules to inhibit melanogenesis .…”

“…4,5 We previously reported the efficacy of 0.1% 4nBR cream with or without liposomal encapsulation in the treatment melasma in a series of randomized, double-blind, vehicle-controlled, split-face studies. 6,7 Resveratrol (RSV) not only binds to tyrosinase directly but also regulates various melanogenic signaling molecules to inhibit melanogenesis. 8 Though clinical use of RSV has been limited yet, its prodrug and hybrid compound have been shown to inhibit UV-induced pigmentation.…”