Archivos por año: 2021

Influence of CYP2D6 Phenotypes on the Pharmacokinetics of Aripiprazole and Dehydro-Aripiprazole Using a Physiologically Based Pharmacokinetic Approach

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,…

Clinical Relevance of Novel Polymorphisms in the Dihydropyrimidine Dehydrogenase (DPYD) Gene in Patients with Severe Fluoropyrimidine Toxicity: A Spanish Case-Control 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…

Effects of Cytochrome P450 and Transporter Polymorphisms on the Bioavailability and Safety of Dutasteride and Tamsulosin

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…

ABCB1 C3435T, G2677T/A and C1236T variants have no effect in eslicarbazepine pharmacokinetics

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…

Variants in COMT, CYP3A5, CYP2B6, and ABCG2 Alter Quetiapine Pharmacokinetics

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…

The pharmacogenetics of treatment with olanzapine

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…

PriME-PGx: La Princesa University Hospital Multidisciplinary Initiative for the Implementation of Pharmacogenetics

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…

Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis

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…

Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis

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…

Genetic Polymorphisms Associated With the Pharmacokinetics, Pharmacodynamics and Adverse Effects of Olanzapine, Aripiprazole and Risperidone

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…