Department of Biological Science and Nursing, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Department of Plastic, Reconstructive and Aesthetic Surgery, Toyama University Hospital, Toyama, Toyama, Japan.
Xenobiotica. 2024 May;54(5):226-232. doi: 10.1080/00498254.2024.2344664. Epub 2024 Apr 24.
Various cytochrome P450 enzymes (CYPs) that contribute to drug metabolism are expressed in the skin. However, variation among individuals in CYP expression profiles is not well-understood.To investigate CYPs related to the metabolism of transdermal preparations in Japan, multiple skin tissue specimens of individuals of Japanese descent were prepared, and the mRNA expression levels of , , and were measured. Associations between the expression patterns of these CYPs and body mass index (BMI) were also investigated.There were considerable individual differences in epidermal mRNA expression levels, and showed a weak positive correlation with mRNA expression levels. In contrast to previous results for other organs, epidermal mRNA expression levels showed a weak positive correlation with BMI. in the epidermis may have been locally enhanced as a defence mechanism against xenobiotics in response to impaired barrier function. These differences in mRNA expression in the skin may affect the transdermal absorption of drugs, such as lidocaine and fentanyl, which are metabolised by multiple overlapping CYPs.Our study provides new insights into drug metabolism in the skin. These results are valuable for predicting drug effects and transdermal drug transfer rates in Japanese patients.
各种参与药物代谢的细胞色素 P450 酶(CYPs)在皮肤中表达。然而,个体 CYP 表达谱的差异尚不清楚。为了研究与日本透皮制剂代谢相关的 CYP,我们准备了多个具有日本血统的个体的皮肤组织标本,并测量了 、 和 的 mRNA 表达水平。还研究了这些 CYP 的表达模式与体重指数(BMI)之间的关联。表皮 mRNA 表达水平存在相当大的个体差异,并且 与 mRNA 表达水平呈弱正相关。与其他器官的先前结果相反,表皮 mRNA 表达水平与 BMI 呈弱正相关。表皮中的 可能是作为对屏障功能受损的外来物质的防御机制而局部增强的。皮肤中这些 mRNA 表达的差异可能会影响多种重叠 CYP 代谢的药物(如利多卡因和芬太尼)的透皮吸收。我们的研究为皮肤中的药物代谢提供了新的见解。这些结果对于预测日本患者的药物作用和透皮药物传递率具有重要价值。