title: Pharmacogenetics in older people: what we know and what we need to know.
abstract: The prevalence of therapeutic failures (TFs) and adverse drug reactions (ADRs) markedly increased in older subjects. However, both TFs and ADRs did not always appear related to the presence of multiple pharmacologic treatments, a common status in subjects aged 65 and over. Instead, they seem more related to variations in the genes encoding protein metabolizing and transporting drugs. Thus, variations in these proteins may account for the inter-individual differences observed in drug efficacy, including the most severe clinical consequences TFs and ADRs. The genetics of drug metabolizing enzymes (DMEs) and drug transporters (DTs) is a very active area of multidisciplinary research, overlapping the fields of medicine, biology, pharmacology, and genetics. These proteins are virtually responsible for metabolism and disposition, and thus the efficacy, of a number of drugs currently used in clinical practice. This article explored some basic concepts of the pharmacogenetics of DMEs and DTs. We also focused current knowledge of the genetic basis of TFs and ADRs of the most common drugs currently used in geriatric clinics. The knowledge of what we know and what we need to know is needed to advance the application of pharmacogenetics in clinical practice, in order to introduce personalized treatments for elderly people.
authors.affiliation: Gerontology and Geriatric Research Laboratory, Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy. dseripa@operapadrepio.it
authors.forename: Davide
authors.initials: D
authors.lastname: Seripa
authors.forename: Giulia
authors.initials: G
authors.lastname: Paroni
authors.forename: Maria
authors.initials: M
authors.lastname: Urbano
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Santini
authors.forename: Grazia
authors.initials: G
authors.lastname: D'Onofrio
authors.forename: Alberto
authors.initials: A
authors.lastname: Pilotto
mesh_terms: D000368:Aged; D001692:Biological Transport; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010597:Pharmacogenetics; D017211:Treatment Failure
chemical_list: D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System