mRNA expression levels of cytochrome P450 CYP1A2, CYP3A4, and CYP3A5 in the epidermis: a focus on individual differences among Japanese individuals

Abstract

1. 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.

2. 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 CYP1A2, CYP3A4, and CYP3A5 were measured. Associations between the expression patterns of these CYPs and body mass index (BMI) were also investigated.

3. There were considerable individual differences in epidermal CYP1A2 mRNA expression levels, and CYP1A2 showed a weak positive correlation with CYP3A4 mRNA expression levels. In contrast to previous results for other organs, epidermal CYP3A4 mRNA expression levels showed a weak positive correlation with BMI.

4. CYP3A4 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.

5. 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.

Keywords:

• biological variation
• cytochrome P450
• drug metabolism
• obesity
• skin absorption

Acknowledgments

The authors thank the patients who participated in this study. The authors also thank Maho Asao for their technical assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, TA, upon reasonable request.

Additional information

Funding

This work was supported by grants-in-aid from the Yokohama Foundation for the Advancement of Medical Science and the Nakatomi Foundation.