Italian 
English Approccio combinato tra il monitoraggio terapeutico del farmaco (TDM) e farmacogenetica per l’applicazione della medicina personalizzata nella pratica clinica
Combined approach of TDM and pharmacogenetics for application of personalized medicine in the clinical practice
AUTORI
1 Laboratorio di Malattie Metaboliche e Biologia del Farmaco, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italia
2 Laboratorio di Genetica medica, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italia
3 Centro Antiveleni Pediatrico, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italia
4 Malattie Infettive ad alta complessità, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma, Italia
ABSTRACT
Combined approach of TDM and pharmacogenetics for application of personalized medicine in the clinical practice
Therapeutic Drug Monitoring (TDM) can be defined as the assessing of the adequacy of the drug plasma concentrations to a target concentration or to a concentration window at a specific time in a dosing interval. Following appropriate clinical interpretation and according to the drug pharmacokinetic/pharmacodynamic (PK/PD) properties, this evaluation can guide dosing optimization. However, finding the optimal dosing in order to guarantee a therapeutic exposure remains complicated. Sources of PK variability, including age, genetic heritage, and disease conditions, influence the chances of achieving adequate therapeutic outcomes. Another important aspect related to drug efficacy and safety is the Pharmacogenetics (PGx). Genetic variants or single nucleotide polymorphisms (SNPs) in genes encoding for metabolizing enzymes and membrane carriers, may affect drug response and/or toxicity. A combination of TDM and PGx could represent a personalized approach in clinical practice especially for off-label drugs used in polytherapy and characterized by a narrow therapeutic index. TDM combined to PGx represents an useful tool that could help clinicians in tailoring pharmacological therapies. We present here three case reports related to pediatric patients who have shown adverse drug reactions in response to therapies with phenytoin (PHT), voriconazole (VO) and isoniazid (INH).