Mechanisms of ketamine-involved regulation of cytochrome P450 gene expression

作者:Chen Jui Tai; Chen Ruei Ming*
来源:Expert Opinion on Drug Metabolism and Toxicology, 2010, 6(3): 273-281.
DOI:10.1517/17425250903505108

摘要

Importance of the field: ketamine, a widely used intravenous anesthetic agent, is biotransformed by cytochrome P450s (CYPs). Considerable attention is devoted to the ketamine-involved regulation of CYP gene expression. Assessing how ketamine regulates CYP gene expression is significant in recognizing the pharmacology of this anesthetic agent and its clinical application. Areas covered in this review: In this review, the authors discuss the effects of ketamine on the regulation of CYP gene expression and its possible mechanisms from the aspects of cytoskeletal remodeling, mitochondrial dysfunction, and alterations of intracellular ATP levels and calcium homeostasis. What the reader will gain: This review may provide readers with more clues for recognizing and avoiding possible ketamine-drug interactions. Take home message: Ketamine may inhibit CYP3A4 expression possibly through reducing calcium mobilization and mitochondrial ATP synthesis and consequently disturbing cytoskeleton remodeling.