11 research outputs found
Ad Inauguralem Orationem, de Compendiosa scholisque apta Docendi Ratione, qua Nutu divino Rectoris Munus in Ascaniensium Lyceo Die Martii rite auspicabatur publice pronunciandam ...
High-Frequency Conductivity of Hot Carriers in Semiconductors with Non-Parabolic Dispersion Law in the Presence of a Magnetic Field
L-N-Acetyl-Cysteine Protection Against Cisplatin-Induced Auditory Neuronal and Hair Cell Toxicity
Effect of polymorphisms on the pharmacokinetics, pharmacodynamics and safety of sertraline in healthy volunteers
Sertraline is a selective serotonin reuptake inhibitor widely metabolized in the liver by cytochrome P450 (CYP) enzymes. Besides, it is a Pâglycoprotein substrate. Moreover, serotonin transporters and serotonin receptors are involved in its efficacy and safety. The aim of this study was to evaluate the role of polymorphisms of metabolizing enzymes, transporters and receptors on the pharmacokinetics, pharmacodynamics and tolerability of sertraline in healthy volunteers. Fortyâsix healthy volunteers (24 men and 22 women) receiving a 100âmg single oral dose of sertraline were genotyped for 17 genetic variants of CYP enzymes (CYP2B6, CYP2C9, CYP2C19, CYP2D6), ATPâbinding cassette subfamily B member 1 (ABCB1), solute carrier family 6 member 4 (SLC6A4), 5âhydroxytryptamine receptor 2A (HTR2A) and 5âhydroxytryptamine receptor 2C (HTR2C) genes. Pharmacokinetic and pharmacodynamic parameters were similar in men and women. Polymorphisms in CYP2C19 and CYP2B6 genes influenced sertraline pharmacokinetics, with a greater effect of CYP2C19. Individuals carrying defective alleles for CYP2C19 and CYP2B6 showed higher area under the curve (AUC) and halfâlife (T1/2). Moreover, CYP2C19*17 was related to a decreased AUC and T1/2. No significant effect was found for polymorphisms in CYP2C9, CYP2D6 and ABCB1 on sertraline pharmacokinetics. Sertraline had a small heart rateâlowering effect, directly related to maximum concentration (Cmax) and the presence of ABCB1 minor alleles. Sertraline had no significant effect on blood pressure and QTc. There was a tendency to present more adverse drug reactions in women and individuals with higher AUC of sertraline, such as CYP2C19 intermediate metabolizers and CYP2B6 G516T T/T individuals.F. Abad-Santos and D. Ochoa have been consultants or investigators in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Chemo, Cinfa, FAES,FarmalĂder, Ferrer, GlaxoSmithKline, Galenicum, Gilead, Jans-sen-Cilag, Kern, Normon, Novartis, Servier, Silverpharma,Teva and Zambon. M. Saiz-Rodriguez is co-financed by ConsejerĂa de EducaciĂłn, Juventud y Deporte from Comunidad de Madrid and Fondo Social Europeo.Peer reviewe