Browsing by Author "Talegón, María"

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.

Aims-. This study evaluated the influence of pharmacogenetics in psoriatic patients treated with adalimumab and/or infliximab. Materials and methods-. Prospective observational study evaluating the association of 124 polymorphisms with the response to adalimumab or infliximab (PASI75) in patients with moderate-to-severe plaque psoriasis at 3 months (N=95) and 6 months of treatment (N=90). Significant SNPs for univariate analysis were subjected to multivariate analysis. Results/Conclusions-. Five SNPs were associated with PASI75 at 3 months: rs6661932 (IVL), rs2546890 (IL12B), rs2145623 (NFKBIA), rs9304742 (ZNF816A) and rs645544 (SLC9A8). Furthermore, rs1061624 (TNFR1B) was associated with PASI75 at 6 months. Nevertheless, these biomarkers should be validated in large-scale studies before implementation in clinical practice.