BUSCADOR RECOLECTA

[Adverse Drug Reactions and CT] The xls file shows relevant information about the treatment with aripiprazole and olanzapine, as well as about their possible adverse effects and the frequency with which they occur. [Genotypes] This is a doc files where It is showm the genotype and phenotype frequencies of the analysed polymorphisms, [Objective] To assess adverse events (AEs) and safety of aripiprazole (ARI) and olanzapine (OLA) treatment. [Conclusions] OLA induced more cardiovascular changes; however, more ADRs were registered to ARI. In addition, some polymorphisms may explain the difference in the incidence of these effects among subjects., European Comission ITN Treatment H2020-MSCA-ITN-721236, Peer reviewed

The data generated or analysed during this study are obtained included in the clinical trial registry name, URL and registration number: TREATMENT-HV; EUDRACT 2018-000744-26; https://eudract.ema. europa.eu/. File1 Adverse events after the treatment with antipsychotics, Short-term treatment with aripiprazole and olanzapine had a significant influence on the metabolic parameters. However, it seems that aripiprazole provokes less severe metabolic changes., European Comission ITN Treatment H2020-MSCA-ITN-721236, Peer reviewed

File 1. This xls files shows the data related to the main charateristics used for the development and validation of the new method as long as the measures for letting assure the repeatability and intermediate precision and accuracy values. The results obtained for the pharmacokinetic parameters are also included in the file File 2 This jpg file shows the product ion spectra and chemical structures of the antipsychotics and their metabolites obtained by collision-induced dissociation (CID) of the indicated precursor ions [M+H]+. The fragmentation patterns of all analytes are indicated by an arrow on their chemical structure of each analyte. The results are presented as the percentage of counts versus Mass-to-Charge (m/z). All mass peaks have been normalized to the most abundant, A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated in human plasma for the simultaneous determination of aripiprazole (ARI) and its metabolite dehydro-aripiprazole (DARI); olanzapine (OLA), risperidone (RIS), paliperidone (PAL), quetiapine (QUE), clozapine (CLO) and caffeine (CAF). CAF is included to the method because it can have an influence on drug metabolism due to competitive inhibition. The above mentioned compounds and their isotope-labeled internal standards were extracted from 200 µL human plasma samples by both, effective phospholipids-eliminating three-step microelution-solid-phase extraction (µ-SPE) and protein precipitation (PPT) for comparison. A combination of formic acid (0.2%)-acetonitrile (pH 3.0; 65:35, v/v) was used as mobile phase and the chromatogram was run under gradient conditions at a flow rate of 0.6 mL/min. Run time lasted 6 min, followed by a re-equilibration time of 3 min. All analytes were monitored by mass spectrometric detection operating in multiple reaction monitoring mode and the method was validated covering the corresponding therapeutic ranges: 0.18-120 ng/mL for ARI, 0.25-80 ng/mL for DARI, 1.00-100 ng/mL for OLA, 0.70-60 ng/mL for RIS, 0.20-30 ng/mL for PAL, 0.50-160 ng/mL for QUE, 0.50-1000 ng/mL for CLO, and finally 1200-3700 ng/mL for CAF. The method was validated based on the recommendations of regulatory agencies through tests of precision, accuracy, extraction recovery, identity confirmation, trueness, matrix effect, process efficiency, stability, selectivity, linearity and carry-over effect fulfilling the guideline requirements. Our µ-SPE method results in the elimination of more than 99% of early eluting and more than 92% of late-eluting phospholipids compared to PPT. Additionally, the method was successfully applied for quantifying ARI and OLA plasma concentrations from healthy volunteers., European Comission ITN Treatment H2020-MSCA-ITN-721236, Peer reviewed

File 1. Demographic characteristics of the volunteers from the aripiprazole study. File 2. Prolactin pharmacokinetic parameters after aripiprazole and ibuprofen administration. This xls file shows the modifications in the prolactin concentrations after the administration of aripiprazole or ibuprofen A It is been shown the prolactin concentrations versus time in women and men treated with aripiprazole compared to ibuprofen File 3 Genotype Matrix. The xls file show the detected genetic polymorphism associated with the effects of aripiprazole File 4 Aripiprazole and dehydro-aripiprazole pharmacokinetic parameters. File 5 The influence of polymorphisms on prolactin concentrations., Aripiprazole treatment in schizophrenic patients was previously associated with lower or normalized prolactin levels. Genetic variants in cytochrome P450 (CYP) (CYP2D6), dopamine receptor (DRD2, DRD3) and serotonin receptor (HTR2A, HTR2C) genes were previously associated with antipsychotic-induced hyperprolactinaemia. Our aim was to evaluate whether aripiprazole affects prolactin secretion and its relationship with pharmacogenetics. Thirty-one healthy volunteers receiving a 10-mg single oral dose of aripiprazole were genotyped for 12 polymorphisms in CYP2D6, DRD2, DRD3, HTR2A and HTR2C genes by qPCR. Aripiprazole and dehydro-aripiprazole plasma concentrations were measured by HPLC-MS/MS. Prolactin concentrations of the 31 volunteers taking aripiprazole and 12 volunteers receiving ibuprofen were determined by ELISA. Prolactin concentrations after ibuprofen intake were considered as control, since it is known to cause no effect. Prolactin concentrations were slightly higher in the aripiprazole group compared to the ibuprofen group. All prolactin pharmacokinetic parameters were higher in females than in males. CYP2D6 poor and intermediate metabolizers had notably higher prolactin Cmax and AUC0-12 than normal and ultrarapid metabolizers. The DRD3 rs6280 polymorphism affected prolactin levels: volunteers carrying Ser/Ser genotype had significantly lower prolactin levels than volunteers carrying the Gly allele. Furthermore, HTR2C rs3813929 C/C homozygotes had significantly lower prolactin levels than T allele carriers. Nevertheless, aripiprazole did increase prolactin levels compared to ibuprofen., European Comission ITN Treatment H2020-MSCA-ITN-721236, Peer reviewed

File 1. Adverse events_TREATMENT The xls file shows relevant information about the treatment with aripiprazole and olanzapine, as well as about their possible adverse effects and the frequency with which they occur. File 2. Genotype Matrix. The xls file show the detected genetic polymorphism associated with the effects of aripiprazole and olanzapine, Aripiprazole altered pupil contraction. Olanzapine caused significant prolactin and weight elevation. Glucose levels in glucose tolerance test were higher after olanzapine treatment. Moreover, olanzapine had more cardiovascular effects than aripiprazole. However, aripiprazole was associated to more psychiatric and nervous system adverse drug reactions. Many polymorphisms may influence pupillometric and metabolic parameters along with cardiovascular changes and adverse events. Moreover, several polymorphisms had an effect on aripiprazole, dehydro-aripiprazole and olanzapine pharmacokinetics. It seems that aripiprazole provokes less severe metabolic and cardiovascular changes, however, more adverse drug reactions were registered to it compared to olanzapine., European Comission ITN Treatment H2020-MSCA-ITN-721236, Peer reviewed