박진우 (성균관대학교)

이상규 (성균관대학교)

박진우 (성균관대학교)

이다인 (성균관대학교)

이종호 (성균관대학교)

이윤서 (성균관대학교)

임유진 (성균관대학교)

이상규 (성균관대학교)

 Synthetic dyes are widely used in industrial, pharmaceutical, and biomedical fields, yet several are being re-evaluated for therapeutic applications, raising concerns about potential drug-drug interactions (DDIs) with co-administered medications. This study investigated the inhibitory effects of three synthetic dyes-methylene blue (MB), crystal violet (CV), and brilliant blue R (BBR)-on major cytochrome P450 (CYP) enzymes using human liver microsomes (HLMs). MB showed strong, selective inhibition of CYP1A2-catalyzed phenacetin O-deethylation (IC₅₀ = 0.24 µM), while CV selectively inhibited CYP2D6-catalyzed dextromethorphan O-deethylation (IC₅₀ = 23.7 µM). BBR showed negligible inhibitory activity against all CYP isoforms tested. Kinetic analyses using Dixon and Lineweaver-Burk plots revealed that MB inhibits CYP1A2 in a reversible, competitive manner with a Ki value of 0.639 µM, and CV inhibits CYP2D6 in a reversible, mixed-type manner with a Ki and Ki’ values of 0.630 µM and 15.9 µM, respectively, with no evidence of time-dependent inhibition for either compound. These findings highlight the need to anticipate DDIs when MB or CV are co-administered with CYP1A2 or CYP2D6 substrate medications, respectively, and demonstrate that not all hazardous dyes pose equivalent DDI risk via CYP inhibition.