Identification of Drugs Acting as Perpetrators in Common Drug Interactions in a Cohort of Geriatric Patients from Southern Italy and Analysis of the Gene Polymorphisms That Affect Their Interacting Potential
Mauro Cataldi,
Camilla Celentano,
Leonardo Bencivenga,
Michele Arcopinto,
Chiara Resnati,
Annalaura Manes,
Loreta Dodani,
Lucia Comnes,
Robert Vander Stichele,
Dipak Kalra,
Giuseppe Rengo,
Francesco Giallauria,
Ugo Trama,
Nicola Ferrara,
Antonio Cittadini,
Maurizio Taglialatela
Affiliations
Mauro Cataldi
Department of Neuroscience, Reproductive Sciences and Dentistry, Federico II University of Naples, Via Sergio Pansini 5, 80131 Naples, Italy
Camilla Celentano
Department of Neuroscience, Reproductive Sciences and Dentistry, Federico II University of Naples, Via Sergio Pansini 5, 80131 Naples, Italy
Leonardo Bencivenga
Department of Translational Medical Sciences, Federico II University of Naples, Via Sergio Pansini 5, 80131 Naples, Italy
Michele Arcopinto
Department of Translational Medical Sciences, Federico II University of Naples, Via Sergio Pansini 5, 80131 Naples, Italy
Chiara Resnati
Department of Neuroscience, Reproductive Sciences and Dentistry, Federico II University of Naples, Via Sergio Pansini 5, 80131 Naples, Italy
Annalaura Manes
Department of Neuroscience, Reproductive Sciences and Dentistry, Federico II University of Naples, Via Sergio Pansini 5, 80131 Naples, Italy
Loreta Dodani
Department of Neuroscience, Reproductive Sciences and Dentistry, Federico II University of Naples, Via Sergio Pansini 5, 80131 Naples, Italy
Lucia Comnes
Datawizard, Via Salaria 719a, 00138 Rome, Italy
Robert Vander Stichele
Heymans Institute of Pharmacology, Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium
Dipak Kalra
Heymans Institute of Pharmacology, Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium
Giuseppe Rengo
Department of Translational Medical Sciences, Federico II University of Naples, Via Sergio Pansini 5, 80131 Naples, Italy
Francesco Giallauria
Department of Translational Medical Sciences, Federico II University of Naples, Via Sergio Pansini 5, 80131 Naples, Italy
Ugo Trama
General Directorate for Health Protection and Coordination of the Regional Health System, Regione Campania, Centro Direzionale Is. C3, 80132 Naples, Italy
Nicola Ferrara
Department of Translational Medical Sciences, Federico II University of Naples, Via Sergio Pansini 5, 80131 Naples, Italy
Antonio Cittadini
Department of Translational Medical Sciences, Federico II University of Naples, Via Sergio Pansini 5, 80131 Naples, Italy
Maurizio Taglialatela
Department of Neuroscience, Reproductive Sciences and Dentistry, Federico II University of Naples, Via Sergio Pansini 5, 80131 Naples, Italy
Background: Pharmacogenomic factors affect the susceptibility to drug–drug interactions (DDI). We identified drug interaction perpetrators among the drugs prescribed to a cohort of 290 older adults and analysed the prevalence of gene polymorphisms that can increase their interacting potential. We also pinpointed clinical decision support systems (CDSSs) that incorporate pharmacogenomic factors in DDI risk evaluation. Methods: Perpetrator drugs were identified using the Drug Interactions Flockhart Table, the DRUGBANK website, and the Mayo Clinic Pharmacogenomics Association Table. Allelic variants affecting their activity were identified with the PharmVar, PharmGKB, dbSNP, ensembl and 1000 genome databases. Results: Amiodarone, amlodipine, atorvastatin, digoxin, esomperazole, omeprazole, pantoprazole, simvastatin and rosuvastatin were perpetrator drugs prescribed to >5% of our patients. Few allelic variants affecting their perpetrator activity showed a prevalence >2% in the European population: CYP3A4/5*22, *1G, *3, CYP2C9*2 and *3, CYP2C19*17 and *2, CYP2D6*4, *41, *5, *10 and *9 and SLC1B1*15 and *5. Few commercial CDSS include pharmacogenomic factors in DDI-risk evaluation and none of them was designed for use in older adults. Conclusions: We provided a list of the allelic variants influencing the activity of drug perpetrators in older adults which should be included in pharmacogenomics-oriented CDSSs to be used in geriatric medicine.
