Clin Transl Sci. 2023 Dec 22. doi: 10.1111/cts.13698. Online ahead of print. ABSTRACT Tramadol is an important minor opioid prescribed for pain management. In this work, we analyzed the well-known impact of CYP2D6 genetic variation and 60 additional variants in eight candidate genes (i.e., ABCG2, SLCO1B1, CYP2D6, CYP2B6, CYP2C19, CYP2C9, CYP3A5 and CYP3A4) on tramadol…
EJHaem. 2023 Sep 27;4(4):1052-1058. doi: 10.1002/jha2.799. eCollection 2023 Nov. ABSTRACT 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…
J Pers Med. 2023 Oct 31;13(11):1566. doi: 10.3390/jpm13111566. ABSTRACT 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., pharmacogenes) could affect their pharmacokinetic processes altering their drug exposure, efficacy, and toxicity. The main objective…
Clin Pharmacol Ther. 2023 Nov 16. doi: 10.1002/cpt.3093. Online ahead of print. NO ABSTRACT PMID:37970726 | DOI:10.1002/cpt.3093
Int J Mol Sci. 2023 Oct 17;24(20):15265. doi: 10.3390/ijms242015265. ABSTRACT 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. Every volunteer was genotyped for…
Clin Transl Sci. 2023 Oct 11. doi: 10.1111/cts.13655. Online ahead of print. ABSTRACT First-time-in-human (FTIH) trials are designed to generate information on the safety, tolerability, as well as the pharmacokinetic and pharmacodynamics profile of new drugs. To ensure the safety of participants, these trials need to be conducted at specifically equipped phase I clinical trial…
Front Med (Lausanne). 2023 Sep 22;10:1215246. doi: 10.3389/fmed.2023.1215246. eCollection 2023. ABSTRACT INTRODUCTION: SARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity. MATERIALS AND METHODS: Retrospective observational study…
J Pers Med. 2023 Jul 29;13(8):1208. doi: 10.3390/jpm13081208. ABSTRACT A cost analysis of thiopurine treatment was carried out in 257 patients, with 153 preemptively genotyped for TPMT 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 (p < 0.001).…
Clin Pharmacol Ther. 2023 Aug 1. doi: 10.1002/cpt.3012. Online ahead of print. ABSTRACT A novel haplotype composed of two non-coding variants, CYP2C18 NM_000772.3:c.*31T (rs2860840) and NM_000772.2:c.819+2182G (rs11188059), referred to as “CYP2C:TG”, was recently associated with ultrarapid metabolism of various CYP2C19 substrates. As the underlying mechanism and clinical relevance of this effect remain uncertain, we analyzed…
Rivaroxaban is a direct inhibitor of factor Xa, a member of direct oral anticoagulant group of drugs (DOACs). Despite being a widely extended alternative to vitamin K antagonists (i.e., acenocoumarol, warfarin) the interindividual variability of DOACs is significant, and may be related to adverse drug reaction occurrence or drug inefficacy, namely hemorrhagic or thromboembolic events.
JAMA Neurol. 2023 Jun 20:e231660. doi: 10.1001/jamaneurol.2023.1660. Online ahead of print. ABSTRACT IMPORTANCE: ApTOLL is a TLR4 antagonist with proven preclinical neuroprotective effect and a safe profile in healthy volunteers. OBJECTIVE: To assess the safety and efficacy of ApTOLL in combination with endovascular treatment (EVT) for patients with ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS: This…
Pharmacogenet Genomics. 2023 Jun 1;33(4):88-89. doi: 10.1097/FPC.0000000000000496. Epub 2023 Apr 25. NO ABSTRACT PMID:37098853 | DOI:10.1097/FPC.0000000000000496
Mol Neurobiol. 2023 Apr;60(4):2070-2085. doi: 10.1007/s12035-022-03180-z. Epub 2023 Jan 5. ABSTRACT Epigenetic changes such as DNA methylation were observed in drug-resistant temporal lobe epilepsy (DR-TLE), a disease that affects 25-30% of epilepsy patients. The main objective is to simultaneously describe DNA methylation patterns associated with DR-TLE in hippocampus, amygdala, surrounding cortex to the epileptogenic zone…
J Pers Med. 2023 Mar 8;13(3):489. doi: 10.3390/jpm13030489. ABSTRACT For patients with type 2 diabetes, metformin is the most often recommended drug. However, there are substantial individual differences in the pharmacological response to metformin. To investigate the effect of transporter polymorphisms on metformin pharmacokinetics in an environment free of confounding variables, we conducted our study…
Front Neurol. 2023 Feb 24;14:1127585. doi: 10.3389/fneur.2023.1127585. eCollection 2023. ABSTRACT In the reperfusion era, a new paradigm of treating patients with endovascular treatment (EVT) and neuroprotective drugs is emerging as a promising therapeutic option for patients with acute ischemic stroke (AIS). In this context, ApTOLL, a Toll-like receptor 4 (TLR4) antagonist with proven neuroprotective effect…
Front Pharmacol. 2023 Feb 2;14:1110460. doi: 10.3389/fphar.2023.1110460. eCollection 2023. ABSTRACT 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…
Pharmaceutics. 2023 Jan 26;15(2):409. doi: 10.3390/pharmaceutics15020409. ABSTRACT (1) Background: this article investigates which PK metrics in a single-dose study (concentration at the end of posology interval, Cτ, partial areas under the curve, pAUCs, or half-value duration, HVD) are more sensitive and less variable for predicting the failure of a prolonged-release product at steady-state that was…
Pharmaceutics. 2023 Jan 25;15(2):404. doi: 10.3390/pharmaceutics15020404. ABSTRACT Amlodipine is an antihypertensive drug with unknown pharmacogenetic biomarkers. This research is a candidate gene study that looked for associations between amlodipine pharmacokinetics and safety and pharmacogenes. Pharmacokinetic and safety data were taken from 160 volunteers from eight bioequivalence trials. In the exploratory step, 70 volunteers were genotyped…
Biomed Pharmacother. 2023 Jan;157:114003. doi: 10.1016/j.biopha.2022.114003. Epub 2022 Nov 11. NO ABSTRACT PMID:36371855 | DOI:10.1016/j.biopha.2022.114003
Blood Adv. 2022 Dec 30:bloodadvances.2022009279. doi: 10.1182/bloodadvances.2022009279. Online ahead of print. ABSTRACT The tyrosine kinase inhibitor dasatinib is approved for Philadelphia chromosome positive leukemia, including chronic myeloid leukemia (CML). While effective and well tolerated, patients typically exhibit a transient lymphocytosis following dasatinib uptake. The underlying physiological process linking dasatinib to lymphocytosis has remained unknown to…
Pharmaceutics. 2022 Dec 29;15(1):113. doi: 10.3390/pharmaceutics15010113. ABSTRACT In recent times, the progress of Clinical Pharmacogenetics has been remarkable […]. PMID:36678742 | PMC:PMC9867244 | DOI:10.3390/pharmaceutics15010113
Pharmacogenomics. 2022 Dec;23(18):949-952. doi: 10.2217/pgs-2022-0161. Epub 2022 Nov 22. NO ABSTRACT PMID:36412207 | DOI:10.2217/pgs-2022-0161
Diabetologia. 2022 Mar;65(3):490-505. doi: 10.1007/s00125-021-05630-0. Epub 2021 Dec 21. ABSTRACT AIMS/HYPOTHESIS: Second-generation antipsychotic (SGA) drugs have been associated with the development of type 2 diabetes and the metabolic syndrome in patients with schizophrenia. In this study, we aimed to investigate the effects of two different SGA drugs, olanzapine and aripiprazole, on metabolic state and islet…
Metabolism. 2022 Dec;137:155335. doi: 10.1016/j.metabol.2022.155335. Epub 2022 Oct 19. ABSTRACT BACKGROUND: Second-generation antipsychotics (SGAs) are a mainstay therapy for schizophrenia. SGA-treated patients present higher risk for weight gain, dyslipidemia and hyperglycemia. Herein, we evaluated the effects of olanzapine (OLA), widely prescribed SGA, in mice focusing on changes in body weight and energy balance. We further…
Pharmacogenomics. 2022 Nov;23(17):913-916. doi: 10.2217/pgs-2022-0142. Epub 2022 Nov 4. NO ABSTRACT PMID:36331025 | DOI:10.2217/pgs-2022-0142
Clin Transl Sci. 2022 Nov;15(11):2613-2624. doi: 10.1111/cts.13386. Epub 2022 Sep 6. ABSTRACT Cinitapride is a gastrointestinal prokinetic drug, prescribed for the treatment of functional dyspepsia, and as an adjuvant therapy for gastroesophageal reflux disease. In this study, we aimed to explore the impact of relevant variants in CYP3A4 and CYP2C8 and other pharmacogenes, along with…
Biomed Pharmacother. 2022 Nov;155:113747. doi: 10.1016/j.biopha.2022.113747. Epub 2022 Sep 24. ABSTRACT Diazepam is a benzodiazepine (BZD) used worldwide for a variety of conditions. Long-term use of diazepam increases the risk for developing tolerance and dependence and for the occurrence of adverse drug reactions (ADRs). CYP3A4 and CYP2C19 mainly metabolize diazepam and are therefore the primary…
Drugs R D. 2022 Sep;22(3):235-243. doi: 10.1007/s40268-022-00394-3. Epub 2022 Aug 2. ABSTRACT 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…
Pharmaceutics. 2022 Sep 21;14(10):2001. doi: 10.3390/pharmaceutics14102001. ABSTRACT Rasagiline is a selective and irreversible inhibitor of monoamine oxidase type B with neuroprotective effect, indicated for the management of Parkinson’s disease. The aim of this work was to evaluate the impact of seven CYP1A2 alleles and of 120 additional variants located in other CYP enzymes (e.g., CYP2C19),…
J Pers Med. 2022 Sep 4;12(9):1452. doi: 10.3390/jpm12091452. ABSTRACT BACKGROUND: Psoriasis can present different phenotypes and could affect diverse body areas. In contrast to the high effectiveness of biological drugs in the treatment of trunk and extremities plaque psoriasis, in palmoplantar phenotypes and in plaque scalp psoriasis, these same drugs usually have reduced efficacy. Anti-TNF…
Cancer Chemother Pharmacol. 2022 Aug;90(2):125-136. doi: 10.1007/s00280-022-04454-y. Epub 2022 Jul 14. ABSTRACT PURPOSE: Imatinib is indicated for treatment of CML, GIST, etc. The population pharmacokinetics (popPK) of imatinib in patients under long-term treatment are reported in literature. Data obtained from bioequivalence trials for healthy subjects were used to evaluate the influence of demographic and pharmacogenetic…
Front Cardiovasc Med. 2022 Aug 4;9:959916. doi: 10.3389/fcvm.2022.959916. eCollection 2022. ABSTRACT OBJECTIVE: To date, the influence of the carboxylesterase 1 (CES1) rs2244613 genotype on the pharmacokinetics (PKs) and safety of dabigatran remains controversial. Hence, a systematic review was performed to study the association between CES1 rs2244613 genotype and the PKs and safety of dabigatran and…
Front Pharmacol. 2022 Jul 6;13:937045. doi: 10.3389/fphar.2022.937045. eCollection 2022. ABSTRACT Background-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. Objectives-We aimed to evaluate the performance of a laboratory alerts system as a method…
Life Sci Alliance. 2022 Jun 9;5(10):e202201545. doi: 10.26508/lsa.202201545. Print 2022 Oct. ABSTRACT We identified an error in the abstract of the article: TPMRSS2 rs75603675 OR is incorrectly indicated. It should read (OR = 2.140) instead of (OR = 0.586). We apologize for this error. However, since the main text is correct, it has no impact…
Life Sci Alliance. 2022 May 30;5(10):e202201396. doi: 10.26508/lsa.202201396. Print 2022 Oct. ABSTRACT 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. Therefore, identification of prognostic biomarkers…
J Pers Med. 2022 May 13;12(5):788. doi: 10.3390/jpm12050788. ABSTRACT Donepezil and memantine are the most common drugs used for Alzheimer’s disease. Their low effectiveness could partly be explained by genetic factors. Thus, we aim to identify Single Nucleotide Polymorphisms (SNPs) associated with pharmacokinetics, pharmacodynamics, and the safety of donepezil and memantine. For this regard, 25…
Adv Ther. 2022 Apr;39(4):1743-1753. doi: 10.1007/s12325-022-02067-8. Epub 2022 Feb 22. ABSTRACT INTRODUCTION: Thiopurine drugs are purine nucleoside analogues used for treatment of different immune-related conditions. To date, different studies highlighted the importance of thiopurine methyltransferase (TPMT) genotyping in patients who initiate treatment with thiopurines to make an adequate dose adjustment. We aimed to investigate the…
Mol Ther Nucleic Acids. 2022 Mar 9;28:124-135. doi: 10.1016/j.omtn.2022.03.005. eCollection 2022 Jun 14. ABSTRACT 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,…
Pharmaceutics. 2022 Mar 3;14(3):559. doi: 10.3390/pharmaceutics14030559. ABSTRACT Acute myeloid leukemia (AML) is a heterogeneous disease characterized by remarkable toxicity and great variability in response to treatment. Plenteous pharmacogenetic studies have already been published for classical therapies, such as cytarabine or anthracyclines, but such studies remain scarce for newer drugs. There is evidence of the relevance…
Front Med (Lausanne). 2022 Feb 23;9:819621. doi: 10.3389/fmed.2022.819621. eCollection 2022. ABSTRACT 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…
J Pers Med. 2022 Feb 12;12(2):270. doi: 10.3390/jpm12020270. ABSTRACT 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…
Pharmaceuticals (Basel). 2022 Jan 8;15(1):78. doi: 10.3390/ph15010078. ABSTRACT 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…
Clin Pharmacokinet. 2021 Dec;60(12):1569-1582. doi: 10.1007/s40262-021-01041-x. Epub 2021 Jun 14. ABSTRACT BACKGROUND AND OBJECTIVES: Aripiprazole is an atypical antipsychotic drug that is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4, which mainly form its active metabolite dehydro-aripiprazole. Because of the genetic polymorphism of CYP2D6, plasma concentrations are highly variable between different phenotypes. In this study,…
Pharmaceutics. 2021 Nov 29;13(12):2036. doi: 10.3390/pharmaceutics13122036. ABSTRACT Among cancer patients treated with fluoropyrimidines, 10-40% develop severe toxicity. Polymorphism of the dihydropyrimidine dehydrogenase (DPYD) 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. Routine genotyping of this gene, which…
Front Pharmacol. 2021 Oct 7;12:718281. doi: 10.3389/fphar.2021.718281. eCollection 2021. ABSTRACT 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…
Biomed Pharmacother. 2021 Oct;142:112083. doi: 10.1016/j.biopha.2021.112083. Epub 2021 Aug 24. ABSTRACT 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…
Pharmaceutics. 2021 Sep 28;13(10):1573. doi: 10.3390/pharmaceutics13101573. ABSTRACT Quetiapine is an atypical antipsychotic widely used for the treatment of schizophrenia and the depressive episodes of bipolar disorder. The aim of this work was to investigate the effect of variants in relevant pharmacogenes in the pharmacokinetics of quetiapine and to exploratorily evaluate adverse drug reaction (ADR) incidence…
Pharmacogenomics. 2021 Sep;22(14):939-958. doi: 10.2217/pgs-2021-0051. Epub 2021 Sep 16. ABSTRACT 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…
J Clin Med. 2021 Aug 24;10(17):3772. doi: 10.3390/jcm10173772. ABSTRACT The implementation of clinical pharmacogenetics in daily practice is limited for various reasons. Today, however, it is a discipline in full expansion. Accordingly, in the recent times, several initiatives promoted its implementation, mainly in the United States but also in Europe. In this document, the genotyping…
JAMA. 2021 Aug 10;326(6):499-518. doi: 10.1001/jama.2021.11330. ABSTRACT IMPORTANCE: Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm. OBJECTIVE: To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes. DATA SOURCES: Trials…
Sci Rep. 2021 Jul 16;11(1):14579. doi: 10.1038/s41598-021-93780-x. ABSTRACT The interplay between T cells, dendritic cells and keratinocytes is crucial for the development and maintenance of inflammation in psoriasis. GADD45 proteins mediate DNA repair in different cells including keratinocytes. In the immune system, GADD45a and GADD45b regulate the function and activation of both T lymphocytes and…
Front Pharmacol. 2021 Jul 14;12:711940. doi: 10.3389/fphar.2021.711940. eCollection 2021. ABSTRACT 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…
Adv Ther. 2021 Jul;38(7):4070-4081. doi: 10.1007/s12325-021-01801-y. Epub 2021 Jun 12. ABSTRACT INTRODUCTION: Bilastine is a second-generation H1 antihistamine indicated for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. On the basis of the demonstrated efficacy and safety of the oral formulation, a new ophthalmic formulation of bilastine was recently developed. Previous preclinical studies had indicated…
J Clin Med. 2021 Jun 30;10(13):2949. doi: 10.3390/jcm10132949. ABSTRACT Patients with venous thromboembolism (VTE) require immediate treatment with anticoagulants such as acenocoumarol. This multicentre randomised clinical trial evaluated the effectiveness of a dosing pharmacogenetic algorithm versus a standard-of-care dose adjustment at the beginning of acenocoumarol treatment. We included 144 patients with VTE. On the day…
Therap Adv Gastroenterol. 2021 Jun 3;14:17562848211018097. doi: 10.1177/17562848211018097. eCollection 2021. ABSTRACT BACKGROUND: Active disease during conception and pregnancy in women with inflammatory bowel disease (IBD) increases the risk of pregnancy complications and adverse neonatal outcomes. The use of IBD treatments during pregnancy should be weighed against their adverse effects on the neonate, but longer-term safety…
Acta Derm Venereol. 2021 May 4;101(5):adv00448. doi: 10.2340/00015555-3794. ABSTRACT Biological drugs targeting tumour necrosis factor are effective for psoriasis. However, 30-50% of patients do not respond to these drugs and may even develop paradoxical psoriasiform reactions. This study search-ed for DNA copy number variations that could predict anti-tumour necrotic factor drug response or the appearance…
Clin Ther. 2021 May;43(5):e86-e102. doi: 10.1016/j.clinthera.2021.03.005. Epub 2021 Apr 1. ABSTRACT PURPOSE: We aimed to elucidate the influence on analgesic effect of genetic polymorphisms in enzymes responsible for biotransformation of tramadol and ibuprofen or other possible genes involved in their mechanism of action. METHODS: The study population comprised 118 patients from a multicenter, randomized, double-blind,…
Front Pharmacol. 2021 Apr 29;12:660639. doi: 10.3389/fphar.2021.660639. eCollection 2021. ABSTRACT Dexketoprofen is the (S)-(+)-enantiomer of racemic ketoprofen, a nonsteroidal anti-inflammatory drug used for the management of different types of pain. To the best of our knowledge, no article was published to date on dexketoprofen pharmacogenetics. Thence, in this work, we aimed to explore the influence…
Front Pharmacol. 2021 Apr 15;12:664465. doi: 10.3389/fphar.2021.664465. eCollection 2021. ABSTRACT Purpose: Albendazole is a benzimidazole carbamate drug with anthelmintic and antiprotozoal activity against intestinal and tissue parasites. It has been described that the administration with meals increases albendazole absorption. Our aim was to compare the systemic exposure in healthy volunteers of two albendazole formulations after…
J Pers Med. 2021 Mar 13;11(3):204. doi: 10.3390/jpm11030204. ABSTRACT Atorvastatin, prescribed for the treatment of hypercholesterolemia, demonstrated overwhelming benefits in reducing cardiovascular morbidity and mortality. However, many patients discontinue therapy due to adverse reactions, especially myopathy. The Dutch Pharmacogenetics Working Group (DPWG) recommends an alternative agent to atorvastatin and simvastatin or a dose adjustment depending…
Medicina (Kaunas). 2020 Dec 20;56(12):719. doi: 10.3390/medicina56120719. ABSTRACT Background and objectives: Psoriasis is a chronic immune-mediated skin disease caused by several complex factors, both environmental and genetic, many of which are still not fully understood. Nowadays, several groups of biological drugs are being used for psoriasis treatment. Although these therapies are very effective, they show…
