Is Dexamethasone a Substrate, an Inducer, or a Substrate-Inducer of CYP3As?

Dexamethasone is a steroidal agent used in the treatment of many different clinical conditions. As such, it is often combined with several drugs from various pharmacological classes. The clinical significance of potential drug-drug interactions involving dexamethasone either as a substrate or as an inducer of cytochrome P450 3As (CYP3As) is not well established due to conflicting results. in vitro studies conducted with human microsomes, primary cultures of human hepatocytes, and clinical studies using various dexamethasone concentrations and doses are reviewed to provide valuable information. Results from these studies demonstrate that CYP3As are clearly involved in the metabolism of dexamethasone, a substrate with weak affinity. However, the potential mechanism for CYP3A induction by dexamethasone remains unclear. Combining results from clinical studies employing different doses, different treatment durations along with evaluation of the baseline CYP3A enzyme activity suggests that dexamethasone could increase CYP3A4 gene expression by 25-30%, a marginally clinically significant effect.

Keywords: CYP; Drug-drug interactions; Drug metabolism; Victim drugs; Substrates; Inducers; in vitro; In vivo

Abbreviations:: CYP: Cytochrome P450; mRNA; Messenger RNA; Cmax: Max Concentration