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Pharmacogenetics of trazodone in healthy volunteers: association with pharmacokinetics, pharmacodynamics and safety

Título : Pharmacogenetics of trazodone in healthy volunteers: association with pharmacokinetics, pharmacodynamics and safety
Autor : Saiz Rodríguez, Miriam
Belmonte, Carmen
Derqui Fernández, Nieves
Cabaleiro, Teresa
Román, Manuel
Ochoa Mazarro, Dolores
Talegón, María
Ovejero Benito, María del Carmen
Abad-Santos, Francisco
Materias: PolymorphismsPharmacodynamics
Editorial : Future Medicine
Citación : Saiz-Rodríguez M, Belmonte C, Derqui-Fernández N, Cabaleiro T, Román M, Ochoa D, Talegón M, Ovejero-Benito MC, Abad-Santos F. Pharmacogenetics of trazodone in healthy volunteers: association with pharmacokinetics, pharmacodynamics and safety. Pharmacogenomics. 2017 Nov;18(16):1491-1502. doi: 10.2217/pgs-2017-0116
Resumen : Aim: The aim was to evaluate the effect of polymorphisms in metabolizing enzymes and transporters on the pharmacokinetics, pharmacodynamics and adverse effects of trazodone in healthy volunteers. Materials & methods: 36 healthy volunteers receiving a single 100-mg oral dose of trazodone were genotyped for 11 variants in CYP3A4, CYP3A5, CYP2D6 and ABCB1 by real-time PCR. Plasma concentrations were measured using liquid chromatography-tandem mass spectrometry method. Results & conclusion: Sex affected the pharmacokinetics of trazodone with higher clearance in women. Polymorphisms in ABCB1, but not in CYP3A or CYP2D6, influenced trazodone pharmacokinetics. Trazodone decreased blood pressure and prolonged the corrected QT interval interval. CYP2D6 and ABCB1 polymorphisms were associated with the incidence of dizziness and prolonged corrected QT interval, respectively. Subjects with adverse drug reactions had lower concentrations of trazodone suggesting its metabolite (m-chlorophenylpiperazine) could be responsible for these effects.
URI : http://hdl.handle.net/10637/15774
Derechos: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
ISSN : 1744-8042
Fecha de publicación : 24-oct-2017
Centro : Universidad San Pablo-CEU
Aparece en las colecciones: Facultad de Farmacia





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