Publications by authors named "Gonzalo Villapalos-Garcia"

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  • * Key findings indicated that certain genetic variations in the TYK2 and VIP genes were linked to a reduced severity of the disease, while variations in TLR7 and OAS1 were associated with increased severity.
  • * The research suggests that these genetic markers could help identify individuals at greater risk for severe COVID-19 outcomes.
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Ramipril is an angiotensin-converting enzyme inhibitor used for hypertension and heart failure management. To date, scarce literature is available on pharmacogenetic associations affecting ramipril. The goal of this study was to investigate the effect of 120 genetic variants in 34 pharmacogenes (i.

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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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  • The study investigates the connection between SARS-CoV-2 viral load (viremia) and genetic variations (SNPs) linked to the severity of COVID-19 in a group of hospitalized patients at University Hospital La Princesa.
  • Out of 340 patients analyzed, only 37.1% had positive viremia, with specific SNPs (like rs2071746 and rs78958998) associated with a higher risk of viremia, while others (like rs11052877 and rs33980500) were linked to a lower risk.
  • The findings suggest that certain genetic variants contribute to differences in SARS-CoV-2 viremia among individuals, highlighting the
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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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The tyrosine kinase inhibitor dasatinib is approved for Philadelphia chromosome-positive leukemia, including chronic myeloid leukemia (CML). Although effective and well tolerated, patients typically exhibit a transient lymphocytosis after dasatinib uptake. To date, the underlying physiological process linking dasatinib to lymphocytosis remains unknown.

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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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By the end of December 2021, coronavirus disease 2019 (COVID-19) produced more than 271 million cases and 5.3 million deaths. Although vaccination is an effective strategy for pandemic control, it is not yet equally available in all countries.

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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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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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Genetic polymorphism in olanzapine-metabolizing enzymes, transporters and drug targets is associated with alterations in safety and efficacy. The aim of this systematic review is to describe all clinically relevant pharmacogenetic information on olanzapine and to propose clinically actionable variants. Two hundred and eighty-four studies were screened; 76 complied with the inclusion criteria and presented significant associations.

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  • The implementation of clinical pharmacogenetics in daily practice has been limited, but it is currently expanding, with initiatives mainly in the U.S. and Europe.
  • Since the establishment of the Pharmacogenetics Unit in 2006, there have been significant genotyping results and an ongoing historical implementation process.
  • La Princesa University Hospital has launched the PriME-PGx initiative, which includes two key projects: the PROFILE project for advanced pharmacogenetic reporting and the GENOTRIAL project for sharing pharmacogenetic findings with clinical trial volunteers.
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Eslicarbazepine acetate is a third-generation anti-epileptic prodrug quickly and extensively transformed to eslicarbazepine after oral administration. Reduction in seizure frequency in patients managed with eslicarbazepine is only partial in the majority of patients and many of them suffer considerable ADRs that require a change of treatment. The P-glycoprotein, encoded by the ABCB1 gene, is expressed throughout the body and can impact the pharmacokinetics of several drugs.

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Olanzapine, aripiprazole and risperidone are atypical antipsychotics or neuroleptics widely used for schizophrenia treatment. They induce various adverse drug reactions depending on their mechanisms of action: metabolic effects, such as weight gain and alterations of glucose and lipid metabolism; hyperprolactinemia and extrapyramidal effects, such as tremor, akathisia, dystonia, anxiety and distress. In this review, we listed polymorphisms associated with individual response variability to olanzapine, aripiprazole and risperidone.

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