Pharmacogenetics of trazodone in healthy volunteers: association with pharmacokinetics, pharmacodynamics and safety.
Pharmacogenomics
; 18(16): 1491-1502, 2017 Nov.
Article
em En
| MEDLINE
| ID: mdl-29061081
ABSTRACT
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trazodona
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Pharmacogenomics
Assunto da revista:
FARMACOLOGIA
/
GENETICA MEDICA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Espanha