Relationship between clock gene expression and and with benzodiazepines.

The present study aimed to clarify the expressions and roles of clock genes involved in drug metabolism in patients taking benzodiazepines (BZDs), as well as the drug metabolism regulators controlled by clock genes for each BZD type. The relationships between the expressions of the clock genes , , and and the drug-metabolizing enzymes and were investigated using livers from BZD-detected autopsy cases. In addition, the effect of BZD exposure on various genes was examined in HepG2 human hepatocellular carcinoma cells. The expressions of , and in the liver were lower in the diazepam-detected group than in the non-detected group. Furthermore, expression correlated with expression. Cell culture experiments showed that the expressions of and decreased, whereas those of and increased after diazepam and midazolam exposure. The results of the analyses of autopsy samples and cultured cells suggested that regulates when exposed to BZD. Understanding the relationship between these clock genes and CYPs may help achieve individualized drug therapy.