Several cytochrome P450 (CYP) CYP3A polymorphisms were associated with reduced enzyme function. We aimed to evaluate the influence of these alleles on pharmacokinetic parameters (PK) several substrates. included 251 healthy volunteers who received a single dose ambrisentan, atorvastatin, imatinib, aripiprazole, fentanyl, amlodipine, donepezil, olanzapine, fesoterodine, or quetiapine. The genotyped for CYP3A4 and CYP3A5 by qPCR. To compare PK across studies, measurements corrected mean each...

ApTOLL is an aptamer that antagonizes Toll-like receptor 4 and improves functional outcomes in models of ischemic stroke myocardial infarction. The aim this study was to characterize the safety pharmacokinetics healthy volunteers. A first-in-human dose-ascending, randomized, placebo-controlled phase I clinical trial assess (30-min infusion intravenously) performed 46 adult male divided into two parts: part included seven single ascending dose levels, B had one multiple cohort. Safety...

Journal Article The relationship between tumour necrosis factor (TNF)‐α promoter and IL12B/IL‐23R genes polymorphisms the efficacy of anti‐TNF‐α therapy in psoriasis: a case–control study Get access E. Gallo, Gallo Department Dermatology Hospital Universitario de la Princesa Instituto Investigación Sanitaria (IP) C/Diego León 62 28006 Madrid Spain Correspondence Elena Gallo. E‐mail: egallo@aedv.es Search for other works by this author on: Oxford Academic Google Scholar T. Cabaleiro,...

The aim of this study was to investigate the effect polymorphisms in cytochrome P450 (CYP) 2D6, CYP3A4 and CYP3A5 enzymes P-glycoprotein (P-gp) on pharmacokinetics safety aripiprazole and, its active metabolite, dehydro-aripiprazole, 148 healthy volunteers from six bioequivalence trials receiving a single oral dose aripiprazole. plasma concentrations both analytes were measured by LC-MS/MS. CYP2D6 (*3,*4,*5,*6,*7,*9 copy number variations), (*20 *22), CYP3A5*3 C3435T, C1236T G2677T/A ABCB1...

Abstract Introduction Epigenetic factors play an important role in psoriasis onset and development. Biological drugs are used to treat moderate‐to‐severe patients resistant conventional systemic drugs. Although they safe effective, some do not respond them. Therefore, it is necessary find biomarkers that could predict response these therapies. Objective To epigenetic biological (ustekinumab, secukinumab, adalimumab, ixekizumab). Materials methods Peripheral blood mononuclear cells ( PBMC s)...

The objective of this study was to analyze the relationship between CYP2D6 genotype and pharmacokinetics pharmacodynamics risperidone. Seventy-one healthy volunteers (36 women 35 men) received a 1-mg single oral dose Six major polymorphisms (CYP2D6*3, *4, *5, *6, *7, *9) duplication were detected. Subjects classified into 4 phenotypic groups: 6 ultrarapid (UMs), 34 extensive (EMs), 25 intermediate (IMs), poor metabolizers (PMs). There clear number active alleles pharmacokinetic parameters...

Abstract Sertraline is a selective serotonin reuptake inhibitor widely metabolized in the liver by cytochrome P450 ( CYP ) enzymes. Besides, it P‐glycoprotein substrate. Moreover, transporters and receptors are involved its efficacy safety. The aim of this study was to evaluate role polymorphisms metabolizing enzymes, on pharmacokinetics, pharmacodynamics tolerability sertraline healthy volunteers. Forty‐six volunteers (24 men 22 women) receiving 100‐mg single oral dose were genotyped for 17...

Abstract P‐glycoprotein, encoded by ABCB 1 , is an ATP ‐dependent drug efflux pump which exports substances outside the cell. Some studies described connections between C3435T polymorphism T allele and lower P‐glycoprotein expression; therefore, homozygous T/T could show higher plasma levels. Our aim was to evaluate effect of on pharmacokinetics 4 antipsychotics (olanzapine, quetiapine, risperidone aripiprazole) antidepressants (trazodone, sertraline, agomelatine citalopram). The study...

Fentanyl is an agonist of the μ-opioid receptor commonly used in treatment moderate-severe pain. In order to study whether pharmacogenetics explains some variability response fentanyl, several genes related fentanyl receptors, transporters and metabolic enzymes have been analysed. Thirty-five healthy volunteers (19 men 16 women) receiving a single 300 μg oral dose were genotyped for 9 polymorphisms cytochrome P450 (CYP) (CYP3A4 CYP3A5), ATP-binding cassette subfamily B member 1 (ABCB1),...

Background: Agomelatine is an agonist of the melatoninergic receptors used for treatment depression. Our aim was to evaluate effect genetic polymorphisms in metabolising enzymes and P-glycoprotein transporter on agomelatine pharmacokinetics pharmacodynamics. Methods: Twenty-eight healthy volunteers receiving a single 25 mg oral dose agomelatine, were genotyped nine cytochrome P450 ( CYP1A2, CYP2C9 CYP2C19) adenosine triphosphate-binding cassette subfamily B member 1 ABCB1), by real-time...

Background/Objectives: Pregabalin is a useful therapeutic option for patients with anxiety or neuropathic pain. Genetic variants in certain genes encoding transporters related to absorption and distribution could have an impact on the efficacy safety of drug. Furthermore, extreme phenotypes metabolic enzymes alter pregabalin-limited metabolism. Methods: In this study, we included 24 healthy volunteers participating bioequivalence clinical trial administered pregabalin 300 mg orally; 23...

Angiotensin II receptor blockers (ARBs) are used to treat hypertension. Most ARBs metabolized by CYP2C9. The aim of this study is evaluate the possible association between sex, polymorphisms in <i>CYP2C8</i> and <i>CYP2C9</i> genes, pharmacokinetics losartan, valsartan, candesartan, telmisartan. population comprised 246 healthy volunteers from seven single-dose clinical trials: 64 two candesartan studies, 43 a telmisartan study, 36 losartan 103 three valsartan studies. DNA was extracted...

Psoriasis improves when IL-17 is blocked. Anti-TNF drugs reduce the signaling pathway, and anti-IL-17 are being developed to treat moderate-to-severe psoriasis. We analyzed three SNPs in IL-17A (rs2275913 rs10484879) IL-17F (rs763780) look for an association with psoriasis and/or response anti-TNF or ustekinumab. included 197 healthy controls 194 patients The results of univariate analysis showed between rs10484879 psoriasis, although this relationship disappeared after adjustment HLA-C...

Objective The pharmacokinetics of olanzapine and response to treatment could be affected by polymorphisms in genes coding for drug‐metabolizing enzymes, transporters, or receptors. aim this study was identify genetic markers predictive pharmacokinetics, pharmacodynamics, adverse effects olanzapine. Methods Sixty‐three healthy volunteers receiving a single 5‐mg oral dose were genotyped 39 variants that related the All analyzed PharmaChip, but DRD2 Taq1A polymorphism determined real‐time...

Objective To identify genetic markers capable of predicting the pharmacokinetics, pharmacodynamics, and adverse effects risperidone. Methods Genotyping was performed in 70 healthy volunteers receiving a single 1 mg oral dose Risperidone hydroxyrisperidone plasma levels were measured using high‐performance liquid chromatography combined with tandem mass spectrometry. Prolactin concentration quantified by direct chemiluminescence. Results Poor CYP2D6 metabolizers showed higher risperidone C...

Abstract Background The pharmacokinetics of proton pump inhibitors (PPIs) may be affected by food intake. We aimed to evaluate the effect on omeprazole, rabeprazole, and pantoprazole. Setting study population comprised 186 healthy volunteers participating in 6 bioequivalence clinical trials. Method Subjects were evaluated determine a high-fat breakfast omeprazole ( n = 36), rabeprazole 69), pantoprazole 81). Main outcome measure Drug plasma concentrations measured using high-performance...

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 atorvastatin simvastatin or a dose adjustment depending on other risk factors statin-induced myopathy SLCO1B1 rs4149056 CC TC carriers. In contrast, Clinical...

Thiopurine drugs are purine nucleoside analogues used for treatment of different immune-related conditions. To date, studies highlighted the importance thiopurine methyltransferase (TPMT) genotyping in patients who initiate with thiopurines to make an adequate dose adjustment. We aimed investigate influence TPMT phenotype, concomitant treatments, and demographic characteristics on incidence adverse reactions (ADRs) start azathioprine (AZA). This was observational retrospective study. The...

Diazepam is a benzodiazepine (BZD) used worldwide for variety of conditions. Long-term use diazepam increases the risk developing tolerance and dependence occurrence adverse drug reactions (ADRs). CYP3A4 CYP2C19 mainly metabolize are therefore primary pharmacogenetic candidate biomarkers. In this work, we aimed to explore impact phenotypes 99 additional variants in other 31 pharmacogenes (including CYP, UGT, NAT2 CES enzymes, ABC SLC transporters) on pharmacokinetic variability safety. 30...

Amlodipine is an antihypertensive drug with unknown pharmacogenetic biomarkers. This research a candidate gene study that looked for associations between amlodipine pharmacokinetics and safety pharmacogenes. Pharmacokinetic data were taken from 160 volunteers eight bioequivalence trials. In the exploratory step, 70 genotyped 44 polymorphisms in different CYP2D6 poor metabolizers (PMs) showed higher half-life (t1/2) (univariate p-value (puv) = 0.039, multivariate (pmv) 0.013, β -5.31, R2...

A total of 126 Candida albicans strains were enzymatically evaluated by the API ZYM system. Four based groups C. are recognized.

Hyperprolactinemia mediated by antagonism of dopaminergic neurotransmission in the pituitary gland is a common adverse effect antipsychotics. Recent studies have suggested that polymorphisms dopamine receptors can affect therapeutic response to Thus, our aim was evaluate whether 2 such (DRD2 Taq1A and DRD3 Ser9Gly) modulate prolactin release healthy volunteers (n = 119) receiving single dose quetiapine (25 mg, n 26), olanzapine (5 57), or risperidone (1 36). The increases maximum...