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Cutaneous in vivo Metabolism of Topical Lidocaine Formulation in Human Skin

Little is known about the metabolising capacity of the human skin in relation to topically applied drugs and formulations. We chose lidocaine as a model compound since the metabolic pathways are well known from studies concerning hepatic metabolism following systemic drug administration. However, the enzymes involved are also expressed in the skin. Hence, the aim of the current study was to investigate the extent of the cutaneous in vivo metabolism of topically applied lidocaine in human volunteers. A dose of 5 mg/cm2 of Xylocaine® (5% lidocaine) ointment was applied onto the buttock skin of the volunteers. After 2 h, residual formulation was removed, and two 4-mm punch biopsies were taken from each volunteer. The quantity of lidocaine extracted from the skin samples (epidermis + dermis) was 109 ± 43 ng/mm2 skin. One metabolite (monoethylglycine xylidide, MEGX) was detected in skin from 7 of the 9 volunteers. The quantity of MEGX formed, relative to the quantity of lidocaine in the skin, was not consistent and ranged from <0.8 to 12.8%. No other metabolites were detected.