Publications by authors named "Gina Mejia-Abril"

Statins are the primary drugs used to prevent cardiovascular disease by inhibiting the HMG-CoA reductase, an enzyme crucial for the synthesis of LDL cholesterol in the liver. A significant number of patients experience adverse drug reactions (ADRs), particularly musculoskeletal problems, which can affect adherence to treatment. Recent clinical guidelines, such as those from the Clinical Pharmacogenetics Implementation Consortium (CPIC) in 2022, recommend adjusting rosuvastatin doses based on genetic variations in the and genes to minimize ADRs and improve treatment efficacy.

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Fesoterodine is one of the most widely used antimuscarinic drugs to treat an overactive bladder. Fesoterodine is extensively hydrolyzed by esterases to 5-hydroxymethyl tolterodine (5-HMT), the major active metabolite. CYP2D6 and CYP3A4 mainly metabolize 5-HMT and are, therefore, the primary pharmacogenetic candidate biomarkers.

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  • - Mirabegron, a medication for overactive bladder, may have its effectiveness and safety influenced by genetic variations in pharmacogenes, prompting research into these effects.
  • - A study involving 79 volunteers assessed the pharmacokinetics and safety of mirabegron, revealing that those with certain genetic variations (like CYP2D6 intermediate metabolizers) experienced longer drug elimination times and more adverse reactions.
  • - Specific genetic variants, such as rs2011425 and rs12708954, were linked to differences in drug clearance and response, indicating that these genetic factors, along with others like UGT1A4, SLC6A2, and SLCO1B1, could help predict patient response to
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  • A study evaluated the immune response of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients to COVID-19 vaccines after stopping methotrexate (MTX) treatment for 1 or 2 weeks compared to those who continued MTX.
  • Patients who paused MTX showed higher levels of antibodies and a stronger T-cell response, particularly in the group that withdrew for 2 weeks.
  • Importantly, stopping MTX did not lead to increased flare-ups of RA or PsA, suggesting that a temporary withdrawal could enhance vaccine effectiveness without risking disease stability.
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Causality algorithms help establish relationships between drug use and adverse event (AE) occurrence. High drug exposure leads to a higher likelihood of an AE being classified as an adverse drug reaction (ADR). However, there is a knowledge gap regarding what concentrations are predictive of ADRs, as this has not been systematically studied.

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  • Tramadol is a minor opioid used for pain management, and this study examines how variations in eight candidate genes (including CYP2D6 and CYP2B6) affect its effectiveness and safety.
  • Researchers recruited 108 post-surgery patients, genotyped them, and measured tramadol metabolite levels, finding that CYP2D6 metabolizer status significantly influenced drug concentration post-administration.
  • The study also revealed that certain genetic profiles (like CYP2B6 poor metabolizers) related to better pain relief and fewer side effects, while other profiles (CYP3A4 intermediate and poor metabolizers) showed higher rates of drowsiness and dizziness, highlighting the need for further research on genetic impacts on tramadol response.
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Tadalafil and finasteride are used in combination for the management of benign prostatic hyperplasia (BPH). Genetic variations in genes involved in the metabolism and transport of tadalafil or finasteride (i.e.

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Drug combination therapy is the most common pharmacological strategy for hypertension management. No pharmacogenetic biomarkers for guiding hypertension pharmacotherapy are available to date. The study population were 64 volunteers from seven bioequivalence trials investigating formulations with valsartan, olmesartan and/or hydrochlorothiazide.

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  • Rivaroxaban is a direct factor Xa inhibitor and part of a drug class known as direct oral anticoagulants (DOACs), which serve as alternatives to traditional blood thinners like warfarin.
  • Despite their popularity, variability in how different individuals respond to DOACs can lead to ineffective treatment or adverse effects such as bleeding or blood clots.
  • A study involving 60 healthy volunteers explored the influence of factors like food intake, sex, biogeographical background, and genetic variations on the metabolism of rivaroxaban, revealing that those with slow NAT2 acetylation had notable changes in drug levels, suggesting a need for further research on genetic impacts on rivaroxaban's effectiveness.
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  • Metformin is the primary treatment for type 2 diabetes, but individual responses vary significantly due to factors like age, sex, and ethnicity.
  • This study is the first to evaluate how demographic factors and various transporter polymorphisms influence metformin pharmacokinetics in healthy individuals, revealing that adjustments for dose-to-weight ratio are crucial in understanding these effects.
  • Findings indicate that multiple patient characteristics must be considered for personalized metformin treatment, as the pharmacokinetics are influenced by a combination of demographics and genetic factors, while certain polymorphisms showed no significant effect.
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  • Amlodipine is an antihypertensive drug, and this study explored genetic factors affecting its pharmacokinetics and safety through a candidate gene approach with data from 160 volunteers.
  • Poor metabolizers of the CYP2D6 gene had a longer drug half-life, while a specific genotype (rs34059508 G/A) was linked to increased drug exposure and potential side effects like thoracic pain and dizziness.
  • This research is the first to establish these genetic associations with amlodipine, indicating a need for further studies before clinical use.
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Venlafaxine pharmacokinetic variability and pharmacotherapy outcomes are well known to be related to CYP2D6 pharmacogenetic phenotype. In contrast, scarce pharmacogenetic information is available nowadays concerning desvenlafaxine, its active metabolite first marketed in 2012. The aim of this study was to evaluate the impact of 29 alleles in 12 candidate genes (e.

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  • Rasagiline is a drug used to treat Parkinson's disease by inhibiting a specific enzyme (monoamine oxidase type B) and has neuroprotective effects.
  • The study assessed the influence of different genetic variations on how the body processes rasagiline in 118 healthy volunteers, finding that certain gene variations affected the drug's absorption and distribution.
  • The findings indicate that genetic differences in drug transporters are more significant in affecting rasagiline's pharmacokinetics than variations in metabolizing enzymes, with minimal adverse reactions reported.
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  • Diazepam, a benzodiazepine, can lead to tolerance and dependence with long-term use, and is primarily metabolized by enzymes CYP3A4 and CYP2C19, indicating the importance of genetic factors in its effectiveness and safety.
  • A study of 30 healthy volunteers revealed that individuals with certain genetic variants, like poor metabolizers of CYP2C19 and CYP2B6, had significantly higher drug concentration levels, suggesting they may require dose adjustments to prevent adverse effects.
  • This research shows a notable link between the CYP2B6 genotype and diazepam metabolism, and hints at other genetic factors that may influence drug behavior, calling for further study on their clinical importance.
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  • Cinitapride is a gastrointestinal drug used for functional dyspepsia and gastroesophageal reflux disease, and this study investigates the effects of genetic variants on its pharmacokinetics and safety.
  • Researchers genotyped healthy volunteers for variants in 19 pharmacogenes, identifying that carriers of the CYP2C8*3 allele had significantly reduced drug exposure, while *4 allele carriers had increased exposure, although not statistically significant.
  • The study helps define pharmacogenetic phenotypes for metabolizers of cinitapride, emphasizing the need for further research to fully understand the implications for other drugs metabolized by CYP2C8.
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Background: Melatonin is an endogenous substance which plays a key role in sleep induction by reducing sleep onset latency; it has been approved by the European Food Safety Authority as a food supplement for exogenous administration. Oniria is a food supplement formulated as 1.98 mg of prolonged-release melatonin tablets; it displays a dual dissolution profile in vitro.

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-Adverse drug reactions (ADRs) are a public health issue, due to their great impact on morbidity, mortality, and economic cost. The use of automatized laboratory alerts could simplify greatly its detection. -We aimed to evaluate the performance of a laboratory alerts system as a method for detecting ADRs, using hyponatremia and rhabdomyolysis as case studies.

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ApTOLL is an aptamer that antagonizes Toll-like receptor 4 and improves functional outcomes in models of ischemic stroke and myocardial infarction. The aim of this study was to characterize the safety and pharmacokinetics of ApTOLL in healthy volunteers. A first-in-human dose-ascending, randomized, placebo-controlled phase I clinical trial to assess safety and pharmacokinetics of ApTOLL (30-min infusion intravenously) was performed in 46 healthy adult male volunteers.

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Background: The use of IL-6 blockers in COVID-19 hospitalized patients has been associated with a reduction in mortality compared to standard care. However, many uncertainties remain pertaining to optimal intervention time, administration schedule, and predictors of response. To date, data on the use of subcutaneous sarilumab is limited and no randomized trial results are available.

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The process of clinical pharmacogenetics implementation depends on patients' and general population's perceptions. To date, no study has been published addressing Spanish patients' opinions on pharmacogenetic testing, the availability of the results, and the need for signing informed consent. In this work, we contacted 146 patients that had been previously genotyped at our laboratory and 46 healthy volunteers that had participated in a bioequivalence clinical trial at the Clinical Pharmacology Department of Hospital Universitario de La Princesa and consented to pharmacogenetic testing for research purposes.

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  • Thiopurine drugs, like azathioprine (AZA), are used to treat various immune-related conditions, and proper dosing based on TPMT genotyping is crucial to minimize adverse reactions (ADRs) in patients starting treatment.* -
  • A study involved 109 patients treated with AZA, mostly older adults, where most were normal metabolizers of TPMT, while a small number were intermediate metabolizers; the initial doses were lower than ideal and increased over time, particularly in normal metabolizers.* -
  • The overall incidence of ADRs was 28.4%, with the most common issues being hepatotoxicity, gastric intolerance, and blood disorders, highlighting the importance of monitoring and adjusting treatments based on metabolic profiles
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Data from several cohorts of coronavirus disease 2019 (COVID-19) suggest that the most common comorbidities for severe COVID-19 disease are the elderly, high blood pressure, and diabetes; however, it is not currently known whether the previous use of certain drugs help or hinder recovery. This study aims to explore the association of previous hospitalisation use of medication on the mortality of COVID-19 disease. A retrospective case-control from two hospitals in Madrid, Spain, included all patients aged 18 years or above hospitalised with a diagnosis of COVID-19.

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Among cancer patients treated with fluoropyrimidines, 10-40% develop severe toxicity. Polymorphism of the dihydropyrimidine dehydrogenase () gene may reduce DPD function, the main enzyme responsible for the metabolism of fluoropyrimidines. This leads to drug accumulation and to an increased risk of toxicity.

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Dutasteride and tamsulosin are one of the first-line combination therapies for the management of benign prostatic hyperplasia (BPH). Despite being more effective than monotherapies, they produce frequent adverse drug reactions (ADRs). Institutions such as Food and Drug Administration and European Medicines Agency recommend precaution with poor metabolizers (PMs) that receive inhibitors and tamsulosin.

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  • Quetiapine is an atypical antipsychotic used primarily for schizophrenia and bipolar disorder, and the study aimed to explore how genetic variations impact its metabolism and potential side effects.
  • 49 healthy participants were included in two clinical trials, where researchers analyzed 80 genetic variants from 19 pharmacogenes, particularly those related to the cytochrome P450 enzyme system.
  • Key findings showed that specific genetic variants (like the rs13306278 T allele) were linked to increased quetiapine exposure and that certain enzymes (CYP3A5 and possibly CYP2B6) significantly influence its metabolism, suggesting the need for more research to validate these results.
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