The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
Original Article
Relationship between low midazolam metabolism by cytochrome P450 3A in mice and the high incidence of birth defects
Satoshi KitaokaJo HatogaiRyuki IimuraYuka YamamotoKonomi ObaMami NakaiYoshiki KusunokiWataru OchiaiKiyoshi Sugiyama
Author information

2018 Volume 43 Issue 1 Pages 65-74


The use of midazolam in early stages of pregnancy has resulted in a high incidence of birth defects; however, the underlying reason is unknown. We investigated expression changes of the CYP3A molecular species and focused on its midazolam metabolizing activity from the foetal period to adulthood. CYP3A16 was the only CYP3A species found to be expressed in the liver during the foetal period. However, CYP3A11 is upregulated in adult mice, but has been found to be downregulated during the foetal period and to gradually increase after birth. When CYP3A16 expression was induced in a microsomal fraction of cells used to study midazolam metabolism by CYP3A16, its activity was suppressed. These results showed that the capacity to metabolize midazolam in the liver during the foetal period is very low, which could hence result in a high incidence of birth defects associated with the use of midazolam during early stages of pregnancy.

Information related to the author
© 2018 The Japanese Society of Toxicology
Previous article