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J. Cosmet. Sci., 57, 291-308 Quly/August 2006) Comparative efficacy and safety of deoxyarbutin, a new tyrosinase-inhibiting agent SAJA H. HAMED, PENKANOK SRIWIRIYANONT, MITCHELL A. deLONG, MARTY 0. VISSCHER, R. RANDALL WICKETT, and RAYMOND E. BOISSY, University of Cincinnati College of Pharmacy (S.H.H.J R.R. W.)J Skin Sciences lnstituteJ Cincinnati Children's Hospital Medical Center (P.S.J M.0. V. J R.E.B.)J Department of ChemistryJ University of Cincinnati (M.A. d. L.) and Department of Dermatology, University of Cincinnati College of Medicine (S.H.H., R.E.B.)J Cincinnati, OH 45267. Accepted for publication March 22, 2006. Synopsis Several tyrosinase inhibitors have been developed and utilized to ameliorate various cutaneous hyperpig­ mentary disorders and complexion discolorations. Deoxyarbutin (dA) (i.e., 4-[(tetrahydro-2H-pyran-2- yl)oxy }phenol), designed using quantitative structure-activity relationships (QSAR), demonstrates effective inhibition of mushroom tyrosinase and skin-lightening capability (1). However, its comparative safety, effectiveness, and reversibility to other known tyrosinase inhibitors in human melanocytes had not been determined. The effect of dA was assessed in cultured human skin cells, on xenographs, and with a clinical trial. Using cultured human melanocytes, the maximum concentration of dA that allowed 95% viability was fourfold greater than for hydroquinone (HQ), indicating that dA is less cytotoxic/cytostatic than HQ. The viability of cultured human keratinocytes and fibroblasts was also less compromised by increasing concen­ trations of dA as opposed to HQ. At the maximum concentration allowing normal cellular viability, dA effectively inhibited tyrosinase activity and melanin content in human melanocytes, whereas HQ was marginally inhibitory. Upon removal of dA, tyrosinase activity and melanin content was normalized within five days. Topical application of dA on human xenografts resulted in a gradual and visually apparent skin lightening effect during an eight-week period. In a clinical trial, dA facilitated fading of pre-tanned skin to a statistically significant greater extent than either HQ or no treatment. These results demonstrate that dA is a potentially saf�, effective, and reversible tyrosinase inhibitor. INTRODUCTION Melanin in an excessive amount and/or altered disposition is the basis for a number of congenital and acquired hyperpigmented skin diseases (2). Hyperpigmentation diseases also manifest psychosocial and cosmetic problems since they are common on sun-exposed Address all correspondence to Raymond E. Boissy. 291