ABSTRACT
Changes in the expression of absorption, distribution, metabolism and excretion (ADME) genes can impact the pharmacokinetics of many small molecule drugs. This chapter aims to provide a broad understanding of the process of induction as well as other phenomenon related to the change in expression levels of ADME genes. Induction of ADME genes is well recognized for its importance in altering the exposure of substrates of the induced enzyme; leading to loss of efficacy and, in some cases, toxicity. There are a number of in vitro and in vivo tools available for preclinical investigations aiming to determine whether or not a drug candidate will be an inducer in vivo. physiologically-based pharmacokinetic modeling and simulation incorporates demographic, genetic, anatomical, physiological, and drug-specific parameters to predict drug concentration-time profiles. Due to the evolutionary divergence of the xenobiotic receptors, the use of animal models has questionable value regarding predictions of outcomes in humans.
