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

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.

• Authors: Miriam Saiz-Rodríguez, Carmen Belmonte, Nieves Derqui-Fernández, Teresa Cabaleiro, Manuel Román, Dolores Ochoa, María Talegón, María C Ovejero-Benito, Francisco Abad-Santos
• Journal: Pharmacogenomics (Pharmacogenomics) Vol. 18 Issue 16 Pg. 1491-1502 (Nov 2017) ISSN: 1744-8042 [Electronic] England
• PMID: 29061081 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Trazodone

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• Adult
• Female
• Genotype
• Healthy Volunteers
• Humans
• Male
• Pharmacogenetics (methods)
• Polymorphism, Single Nucleotide (genetics)
• Trazodone (pharmacokinetics, pharmacology)
• Young Adult