A Toxicologist's Guide to the Preclinical Assessment of Hepatic Microsomal Enzyme Induction.
The assessment of hepatic microsomal enzyme induction at the completion of preclinical toxicology studies in rodents and large mammals provides a wealth of information to the toxicologist and pharmacokineticist regarding how the drug-metabolizing system of the hepatocyte endoplasmic reticulum responded to high-dose levels of a xenobiotic designed for a specific pharmacological target in any of several target organs. The interpretation of these data can be greatly enhanced by a clear understanding of how this system functions and what the immediate and long-term ramifications are to organs and organ systems. This review focuses on how drugs modify the hepatic cytochrome P450 system, how those modifications are detected, the various consequences of these modifications, and some differences in the induction response among species.
Amacher
David E
DE
World-Wide Safety Sciences, Mail Stop 8274-1227, Pfizer Global Research and Development, Groton Laboratories, Groton, Connecticut.