Introduction to Hepatic Drug Metabolizing Enzyme Induction in Drug Safety Evaluation Studies

Abstract

The following three articles represent the output of a combined effort initiated by the Scientific Regulatory Policy Committee of the Society of Toxicologic Pathology to provide a unified review of current scientific practices and relevant literature and provide suggestions regarding the recognition, interpretation, and risk assessment of hepatic drug metabolizing enzyme (DME) induction studies. The core objective was to provide a review that the scientific community including pathologists, regulatory scientists, toxicologists, investigative scientists, and others would find valuable for managing, designing, and interpreting toxicity studies supporting regulatory filings. Three working groups composed of scientists from industry, academia, and regulatory agencies were convened to review the available literature on important aspects of the interpretation and risk assessment of hepatic microsomal DME enzyme induction in three publications. The three reviews are as follows: “Effects of Hepatic Drug Metabolizing Enzyme Induction on Clinical Pathology Parameters in Animals and Man,” Toxicol Pathol “Hepatic Drug Metabolizing Enzyme Induction: Microscopic and Ultrastructural Appearance,” Toxicol Pathol “Hepatic Drug Metabolizing Enzyme Induction and Implications for Preclinical and Clinical Risk Assessment,” Toxicol Pathol The purpose of this introduction is not to summarize the articles but rather to frame the series and to provide a common mechanistic introduction.