Publications by authors named "Pablo Zubiaur"
: Pathophysiological variability in patients with cancer is associated with differences in responses to pharmacotherapy. In this work, we aimed to describe the demographic characteristics and hematological, biochemical, and coagulation variables in a large oncology cohort and to develop, optimize, and provide open access to modeling equations for the estimation of variables potentially relevant in pharmacokinetic modeling. : Using data from 1793 patients with cancer, divided into training ( = 1259) and validation ( = 534) datasets, a modeling network was developed and used to simulate virtual oncology populations.
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- Ezetimibe is a drug that helps reduce cholesterol levels by blocking its absorption in the intestines, but there are currently no established pharmacogenetic guidelines for its use.
- The study involved 96 healthy participants from different trials and focused on 49 genetic variants in 22 genes to determine their impact on ezetimibe's effects.
- Although no strong links were found between genetic variants and ezetimibe's metabolism, some variants showed potential significance in further analyses, suggesting the need for more research in the future.
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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.
The Pharmacogene Variation Consortium (PharmVar) serves as a global repository providing star (*) allele nomenclature for the polymorphic human CYP4F2 gene. CYP4F2 genetic variation impacts the metabolism of vitamin K, which is associated with warfarin dose requirements, and the metabolism of drugs, such as imatinib or fingolimod, and certain endogenous compounds including vitamin E and eicosanoids. This GeneFocus provides a comprehensive overview and summary of CYP4F2 genetic variation including the characterization of 14 novel star alleles, CYP4F2*4 through *17.
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- - The DPYD gene is crucial for encoding dihydropyrimidine dehydrogenase (DPD), which helps metabolize drugs like 5-fluorouracil used in cancer treatment; reduced DPD activity can lead to severe side effects in patients.
- - To improve pharmacogenetic testing for DPYD, a collaboration among various organizations created and distributed 33 characterized DNA samples from Coriell cell lines to different laboratories for testing.
- - These samples allowed the identification of 33 distinct DPYD variants and are intended to enhance quality assurance and control in clinical testing for better patient safety in cancer treatment.
SLCO1B1 and ABCG2 genotype-informed phenotypes are related to variation in ramipril exposure.
Basic Clin Pharmacol Toxicol
September 2024
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.
View Article and Find Full Text PDFMethadone is a mu (μ) opioid receptor agonist used clinically in adults and children to manage opioid use disorder, neonatal abstinence syndrome, and acute and chronic pain. It is typically marketed as a racemic mixture of R- and S-enantiomers. R-methadone has 30-to 50-fold higher analgesic potency than S-methadone, and S-methadone has a greater adverse effect (prolongation) on the cardiac QTc interval.
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- * The study involved 773 healthy volunteers with different UGT1A1 genotypes to assess the prevalence of liver disease and other biochemical markers.
- * Findings showed that intermediate (IM) and poor (PM) metabolizers had higher bilirubin and lower uric acid levels compared to normal metabolizers (NMs), but liver enzyme levels remained normal; suggesting these individuals could be included in future trials.
Estrogens prevent the hypothalamus-periphery crosstalk induced by olanzapine intraperitoneal treatment in female mice: Effects on brown/beige adipose tissues and liver.
Biochim Biophys Acta Mol Basis Dis
June 2024
Olanzapine (OLA) is a highly obesogenic second-generation antipsychotic (SGA). Recently we demonstrated that, contrarily to OLA oral treatment, intraperitoneal (i.p.
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- Proton pump inhibitors (PPIs) are the main treatment for eosinophilic esophagitis (EoE), but about 50% of patients don’t achieve histological remission after treatment.
- This study aimed to discover genetic markers that could predict how well PPIs work for EoE patients and to examine their link to disease characteristics.
- Results showed that patients treated with omeprazole had a significantly better reduction in eosinophil counts compared to other PPIs, and specific genetic variations (rs12368672 and rs167769) may influence both baseline eosinophil counts and the response to treatment.
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.
Methotrexate is an essential drug in the treatment of childhood cancer that is not exempt from toxicities. Glucarpidase is a drug used to reduce the toxic concentration of plasma methotrexate in patients with delayed elimination or at risk of toxicity. We describe the characteristics of a cohort of pediatric patients that received glucarpidase and analyze its role in the treatment of toxicity induced by high doses of methotrexate (HDMTX).
View Article and Find Full Text PDFTadalafil 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.
View Article and Find Full Text PDFDrug 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
A cost analysis of thiopurine treatment was carried out in 257 patients, with 153 preemptively genotyped for and 104 retrospectively genotyped in a Spanish setting. The healthcare cost was significantly higher in patients retrospectively genotyped compared to those who were preemptively genotyped ( < 0.001).
View Article and Find Full Text PDFA novel haplotype composed of two non-coding variants, CYP2C18 NM_000772.3:c.*31T (rs2860840) and NM_000772.
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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.
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.
View Article and Find Full Text PDFIn recent times, the progress of Clinical Pharmacogenetics has been remarkable [...
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