title: Drug metabolism and liver disease: a drug-gene-environment interaction.
abstract: Despite the central role of the liver in drug metabolism, surprisingly there is lack of certainty in anticipating the extent of modification of the clearance of a given drug in a given patient. The intent of this review is to provide a conceptual framework in considering the impact of liver disease on drug disposition and reciprocally the impact of drug disposition on liver disease. It is proposed that improved understanding of the situation is gained by considering the issue as a special example of a drug-gene-environment interaction. This requires an integration of knowledge of the drug's properties, knowledge of the gene products involved in its metabolism, and knowledge of the pathophysiology of its disposition. This will enhance the level of predictability of drug disposition and toxicity for a drug of interest in an individual patient. It is our contention that advances in pharmacology, pharmacogenomics, and hepatology, together with concerted interests in the academic, regulatory, and pharmaceutical industry communities provide an ideal immediate environment to move from a qualitative reactive approach to quantitative proactive approach in individualizing patient therapy in liver disease.
authors.affiliation: a Department of Pharmacology and Toxicology , American University of Beirut Faculty of Medicine , Beirut , Lebanon.
authors.forename: Nathalie K
authors.initials: NK
authors.lastname: Zgheib
authors.affiliation: b Department of Medicine, School of Medicine , University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Branch
mesh_terms: D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D059647:Gene-Environment Interaction; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D008107:Liver Diseases / Q000378:metabolism*; D008955:Models, Cardiovascular; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D057285:Precision Medicine; D014018:Tissue Distribution
chemical_list: D004364:Pharmaceutical Preparations
keywords: CYP enzymes; Drug metabolism; drug-induced liver disease; liver; liver function; models of drug disposition