Metabolizing and eliminating toxic chemicals in the liver are key processes in the body's defense system.
Drug-metabolizing
enzymes (
DMEs) play central roles in such processes. The activity and expression of several key
DMEs are changed in various
liver diseases and thus lead to significantly altered
drug disposition. This phenomenon severely affects the
pharmacotherapy of clinical medications in terms of the safety and efficacy of
drug responses. This review highlights liver physiological functions, altered
DMEs, and altered
drug disposition in
liver diseases. Moreover, the implications of changes in
DMEs on the fate of clinically relevant drugs are also discussed.
Pregnane X receptor and
constitutive androstane receptor are two liver-enriched
nuclear receptors originally defined as
xenobiotic sensors that affect regulation of
DMEs. Altered regulation of
DMEs in
liver diseases contributes to the development of powerful in vitro and in vivo tools to predict
drug responses and options for improved
drug delivery and development. Although a number of treatment drugs are available for
liver diseases, they are limited by their low
drug concentration in the target site, presence of side effects, and instability in the human body. The
nanoparticle drug delivery system has recently attracted research attention because of its potential to offer solutions to current obstacles that involve the use of therapeutic drugs for
liver diseases. Conclusively, this review aims to improve understanding on the regulation of
DMEs in
liver diseases and on corresponding implications in
drug disposition, including novel therapeutic medications.