7,729 results match your criteria cyp2d6

Drug Metabolism in Severe Chronic Obstructive Pulmonary Disease: A Phenotyping 'Cocktail' Study.

Br J Clin Pharmacol 2021 Apr 15. Epub 2021 Apr 15.

Department of Clinical Pharmacology, Christchurch Hospital, New Zealand.

Aims: To evaluate the effect of severe chronic obstructive pulmonary disease (COPD) on drug metabolism by comparing the pharmacokinetics of patients with severe COPD with healthy volunteers and using the modified 'Inje' drug cocktail.

Methods: This was a single-centre pharmacokinetic study with 12 healthy participants and 7 participants with GOLD D COPD. Midazolam 1 mg, dextromethorphan 30 mg, losartan 25 mg, omeprazole 20 mg, caffeine 130 mg, and paracetamol 1000 mg were simultaneously administered and intensive pharmacokinetic sampling was conducted over 8 hours. Read More

View Article and Full-Text PDF

Effects of Xiaochaihu decoction on the expression of cytochrome P450s in rats.

Exp Ther Med 2021 Jun 2;21(6):588. Epub 2021 Apr 2.

Department of Clinical Pharmacy, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China.

Xiaochaihu decoction is one of the most important traditional Chinese medicines that is widely used with other drugs in clinical practice, and may cause drug-drug interactions. However, there is not sufficient experimental evidence for the effects of Xiaochaihu decoction on cytochrome P450s (CYPs). The aim of the present study was to investigate the effects of Xiaochaihu decoction on the mRNA and protein levels of hepatic CYPs. Read More

View Article and Full-Text PDF

The inhibition of CYP1A2, CYP2C9, and CYP2D6 by pterostilbene in human liver microsomes.

Pharmazie 2021 Apr;76(4):155-158

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh.

This study used human liver microsomes to assess pterostilbene's effect on the metabolic activity of cytochrome P450 (CYP) 1A2, CYP2C9, and CYP2D6. The metabolism of their substrates (phenacetin, tolbutamide, and dextromethorphan) was assayed by quantifying their relevant metabolites by HPLC. The IC value was used to express the strength of inhibition, and the value of a volume per dose index (VDI) was used to indicate the metabolic ability of the enzyme. Read More

View Article and Full-Text PDF

Cytochrome P450 Enzyme Inhibition and Herb-Drug Interaction Potential of Medicinal Plant Extracts Used for Management of Diabetes in Nigeria.

Eur J Drug Metab Pharmacokinet 2021 Apr 12. Epub 2021 Apr 12.

Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Rd, Kingston, RI, 02881, USA.

Background And Objective: The use of herbal medicines is common in Africa, and patients often use a combination of herbs and drugs. Concurrent herbal and pharmaceuticals treatments can cause adverse effects through herb-drug interactions (HDI). This study evaluated the potential risk of HDI for five medicinal plants, Vernonia amygdalina, Ocimum gratissimum, Moringa oleifera, Azadirachta indica, and Picralima nitida, using in vitro assays. Read More

View Article and Full-Text PDF

inhibitory effects of glucosamine, chondroitin and diacerein on human hepatic CYP2D6.

Drug Metab Pers Ther 2021 Apr 8. Epub 2021 Apr 8.

School of Pharmacy, International Medical University, No. 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000Kuala Lumpur, Malaysia.

Objectives: Glucosamine, chondroitin and diacerein are natural compounds commonly used in treating osteoarthritis. Their concomitant intake may trigger drug-natural product interactions. Cytochrome P450 (CYP) has been implicated in such interactions. Read More

View Article and Full-Text PDF

Effects of Tianma (Rhizoma Gastrodiae) and Gouteng (Ramulus Uncariae Rhynchophyllae cum Uncis) on cytochrome P450 enzyme activities in rats.

J Tradit Chin Med 2021 04;41(2):284-292

College of Medicine, Southwest Jiaotong University, Chengdu 610031, China.

Objective: To investigate the efficacy of Tianma (Rhizoma Gastrodiae) and Gouteng (Ramulus Uncariae Rhynchophyllae cum Uncis) on cytochrome P450 (CYP450) enzyme activities in rats.

Methods: A cocktail strategy was followed to evaluate the influence of Tianma (Rhizoma Gastrodiae) and Gouteng (Ramulus Uncariae Rhynchophyllae cum Uncis) on the activities of CYP450 isoforms (CYP1A2, CYP3A4, CYP2E1, CYP2C19, CYP2C9, CYP2D6), which were determined by changes in the pharmacokinetic parameters of six probe drugs, theophylline, dapsone, chlorzoxazone, omeprazole, tolbutamide and dextromethorphan. Study groups included, Control group (CG), Tianma (Rhizoma Gastrodiae) group (TM), Gouteng (Ramulus Uncariae Rhynchophyllae cum Uncis) group (GT) and Tianma Gouteng (Gastrodia Uncaria) group (TMGT). Read More

View Article and Full-Text PDF

Trichostatin A sensitizes hepatoma cells to Taxol more than 5-Aza-dC and dexamethasone.

Drug Metab Pers Ther 2021 Apr 5. Epub 2021 Apr 5.

Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt.

Objectives: This work was designed to compare the sensitizing effects of epigenetic modifiers on cancer cells vs. that of glucocorticoids. Also, to evaluate their effects on genes involved in epigenetic changes and drug metabolism. Read More

View Article and Full-Text PDF

Sequence2Script: A Web-Based Tool for Translation of Pharmacogenetic Data Into Evidence-Based Prescribing Recommendations.

Front Pharmacol 2021 18;12:636650. Epub 2021 Mar 18.

Ushiosoft Corporation, Calgary, AB, Canada.

Pharmacogenomic (PGx) testing has emerged as an effective strategy for informing drug selection and dosing. This has led to an increase in the use of PGx testing in the clinic and has catalyzed the emergence of a burgeoning commercial PGx testing industry. However, not all PGx tests are equivalent in their approach to translating testing results into prescribing recommendations, due to an absence of regulatory standards. Read More

View Article and Full-Text PDF

Influence of Genetic Polymorphisms on the Response to Tramadol, Ibuprofen, and the Combination in Patients With Moderate to Severe Pain After Dental Surgery.

Clin Ther 2021 Apr 1. Epub 2021 Apr 1.

Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain; UICEC Hospital Universitario de La Princesa, Plataforma SCReN (Spanish Clinical Reseach Network), Instituto de Investigación Sanitaria La Princesa, Madrid, Spain. Electronic address:

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, placebo-controlled, Phase III clinical trial that assessed the analgesic efficacy and tolerability of a single dose of ibuprofen (arginine)/tramadol 400/37.5 mg compared with ibuprofen arginine 400 mg alone, tramadol 50 mg alone, and placebo in patients with moderate to severe pain after dental surgery. Read More

View Article and Full-Text PDF


Drug Metab Dispos 2021 Apr 2. Epub 2021 Apr 2.

Shanghai University of Traditional Chinese Medicine, China

Methylophiopogonanone A (MOA), an abundant homoisoflavonoid bearing a methylenedioxyphenyl (MDP) moiety, is one of the major consitituents in the Chinese herb This work aims to assess the inhibitory potentials of MOA against cytochrome P450 enzymes, as well as to decipher the molecular mechanisms for CYP inhibition by MOA. The results showed that MOA concentration-dependently inhibited CYPs1A, 2C8, 2C9, 2C19 and 3A in human liver microsomes (HLMs) in a reversible way, with IC values varying from 1.06 μM to 3. Read More

View Article and Full-Text PDF

Comprehensive Virtual Screening of the Antiviral Potentialities of Marine Polycyclic Guanidine Alkaloids against SARS-CoV-2 (COVID-19).

Biomolecules 2021 03 19;11(3). Epub 2021 Mar 19.

Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.

The huge global expansion of the COVID-19 pandemic caused by the novel SARS-corona virus-2 is an extraordinary public health emergency. The unavailability of specific treatment against SARS-CoV-2 infection necessitates the focus of all scientists in this direction. The reported antiviral activities of guanidine alkaloids encouraged us to run a comprehensive in silico binding affinity of fifteen guanidine alkaloids against five different proteins of SARS-CoV-2, which we investigated. Read More

View Article and Full-Text PDF

Pharmacogenetics Approach for the Improvement of COVID-19 Treatment.

Viruses 2021 03 5;13(3). Epub 2021 Mar 5.

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, Mexico.

The treatment of coronavirus disease 2019 (COVID-19) has been a challenge. The efficacy of several drugs has been evaluated and variability in drug response has been observed. Pharmacogenetics could explain this variation and improve patients' outcomes with this complex disease; nevertheless, several disease-related issues must be carefully reviewed in the pharmacogenetic study of COVID-19 treatment. Read More

View Article and Full-Text PDF

Effect of Chronic Administration of 5-(3-chlorophenyl)-4-Hexyl-2,4 -Dihydro-3-1,2,4-Triazole-3-Thione (TP-315)-A New Anticonvulsant Drug Candidate-On Living Organisms.

Int J Mol Sci 2021 Mar 25;22(7). Epub 2021 Mar 25.

Department of Pharmacology, Faculty of Health Sciences, Medical University of Lublin, 20-093 Lublin, Poland.

About 70 million people suffer from epilepsy-a chronic neurodegenerative disease. In most cases, the cause of the disease is unknown, but epilepsy can also develop as the result of a stroke, trauma to the brain, or the use of psychotropic substances. The treatment of epilepsy is mainly based on the administration of anticonvulsants, which the patient must most often use throughout their life. Read More

View Article and Full-Text PDF

Generating a Precision Endoxifen Prediction Algorithm to Advance Personalized Tamoxifen Treatment in Patients with Breast Cancer.

J Pers Med 2021 Mar 13;11(3). Epub 2021 Mar 13.

Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI 48109, USA.

Tamoxifen is an endocrine treatment for hormone receptor positive breast cancer. The effectiveness of tamoxifen may be compromised in patients with metabolic resistance, who have insufficient metabolic generation of the active metabolites endoxifen and 4-hydroxy-tamoxifen. This has been challenging to validate due to the lack of measured metabolite concentrations in tamoxifen clinical trials. Read More

View Article and Full-Text PDF

Inhibitory Effects of Lignans on Cytochrome P450s and Uridine 5'-Diphospho-Glucuronosyl Transferases in Human Liver Microsomes.

Pharmaceutics 2021 Mar 10;13(3). Epub 2021 Mar 10.

BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea.

has been widely used as a traditional herbal medicine to treat chronic coughs, fatigue, night sweats, and insomnia. Numerous bioactive components including lignans have been identified in this plant. Lignans with a dibenzocyclooctadiene moiety have been known to possess anti-cancer, anti-inflammatory, and hepatoprotective activity. Read More

View Article and Full-Text PDF

Bioluminescence Measurement of Time-Dependent Dynamic Changes of CYP-Mediated Cytotoxicity in CYP-Expressing Luminescent HepG2 Cells.

Int J Mol Sci 2021 Mar 11;22(6). Epub 2021 Mar 11.

Chromosome Engineering Research Center, Tottori University, 86 Nishi-cho, Yonago 683-8503, Tottori, Japan.

We sought to develop a cell-based cytotoxicity assay using human hepatocytes, which reflect the effects of drug-metabolizing enzymes on cytotoxicity. In this study, we generated luminescent human hepatoblastoma HepG2 cells using the mouse artificial chromosome vector, in which click beetle luciferase alone or luciferase and major drug-metabolizing enzymes (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) are expressed, and monitored the time-dependent changes of CYP-mediated cytotoxicity expression by bioluminescence measurement. Real-time bioluminescence measurement revealed that compared with CYP-non-expressing cells, the luminescence intensity of CYP-expressing cells rapidly decreased when the cells were treated with low concentrations of aflatoxin B1 or primaquine, which exhibits cytotoxicity in the presence of CYP3A4 or CYP2D6, respectively. Read More

View Article and Full-Text PDF

Potential Utility of Pre-Emptive Germline Pharmacogenetics in Breast Cancer.

Cancers (Basel) 2021 Mar 11;13(6). Epub 2021 Mar 11.

ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT 84108, USA.

Patients with breast cancer often receive many drugs to manage the cancer, side effects associated with cancer treatment, and co-morbidities (i.e., polypharmacy). Read More

View Article and Full-Text PDF

Oxycodone findings and CYP2D6 function in postmortem cases.

Forensic Sci Int Genet 2021 Mar 26;53:102510. Epub 2021 Mar 26.

Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Artillerigatan 12, 58758 Linkoping, Sweden; Division of Drug Research, Department of Biomedical and Clinical Sciences, Faculty of Health and Science, Linkoping University, 58183 Linkoping, Sweden.

Genetic disposition can cause variation in oxycodone pharmacokinetic characteristics and decrease or increase the expected clinical response. In forensic medicine, determination of cause of death or assessing time between drug intake and death can be facilitated by knowledge of parent and metabolite concentrations. In this study, the aim was to investigate if CYP2D6 genotyping can facilitate interpretation by investigating the frequency of the four CYP2D6 phenotypes, poor metabolizer, intermediate metabolizer, extensive metabolizer, and ultra-rapid metabolizer in postmortem cases, and to study if the CYP2D6 activity was associated with a certain cause of death, concentration, or metabolic ratio. Read More

View Article and Full-Text PDF

Exploring the Use of Serum-Derived Small Extracellular Vesicles as Liquid Biopsy to Study the Induction of Hepatic Cytochromes P450 and Organic Anion Transporting Polypeptides.

Clin Pharmacol Ther 2021 Apr 1. Epub 2021 Apr 1.

College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.

Liver-derived small extracellular vesicles (sEVs), prepared from small sets of banked serum samples using a novel two-step protocol, were deployed as liquid biopsy to study the induction of cytochromes P450 (CYP3A4, CYP3A5, and CYP2D6) and organic anion transporting polypeptides (OATP1B1 and OATP1B3) during pregnancy (nonpregnant (T0), first, second, and third (T3) trimester women; N = 3 each) and after administration of rifampicin (RIF) to healthy male subjects. Proteomic analysis revealed induction (mean fold-increase, 90% confidence interval) of sEV CYP3A4 after RIF 300 mg × 7 days (3.5, 95% CI = 2. Read More

View Article and Full-Text PDF

Evaluation of the CYP2D6 haplotype activity scores based on metabolic ratios of 4,700 patients treated with three different CYP2D6 substrates.

Clin Pharmacol Ther 2021 Mar 31. Epub 2021 Mar 31.

Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum 5B, Stockholm, Sweden.

The metabolic activity of the polymorphic CYP2D6 enzyme is dependent on the CYP2D6 genotype; however, the guidelines for translating the genotype into phenotype, which are of relevance for adequate drug dose personalization, are ambiguous. In the present study, retrospective therapeutic drug monitoring data from 4,700 CYP2D6 genotyped patients treated with risperidone, venlafaxine, and/or aripiprazole were analyzed to quantify the effect of CYP2D6 genotype on the CYP2D6 metabolic activities, as measured by metabolic ratios of these substrates. The patients were categorized into diplotypes based on the presence of normal function (CYP2D6Norm), nonfunctional (CYP2D6Nonf) and decreased function (CYP2D6Decr i. Read More

View Article and Full-Text PDF

Genetic variability of and among the Egyptian population.

Pharmacogenomics 2021 Apr 1. Epub 2021 Apr 1.

Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children's Mercy Kansas City & School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USA.

This study investigated major allelic variants of and in Egyptians, an Arabic population for which there is little information regarding these important pharmacogenes. , , , , and gene copy number variation, as well as and were determined with commercially available TaqMan assays in 145 healthy study participants. The alleles identified suggest that the prevalence of poor metabolizers is low as none were found among the 145 subjects investigated. Read More

View Article and Full-Text PDF

Prospects for personalization of depression treatment with genome sequencing.

Br J Pharmacol 2021 Mar 30. Epub 2021 Mar 30.

Laboratory of Pharmacogenomics, Department of Molecular Neuropharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.

The effectiveness of antidepressants in the treatment of major depressive disorder (MDD) varies considerably between patients. With these interindividual differences and a number of antidepressants to choose from, the first choice of treatment often fails to produce improvement in the patient's condition. A substantial part of the variation in response to antidepressants can be explained by genetic factors. Read More

View Article and Full-Text PDF

Prediction of MDMA response in healthy humans: a pooled analysis of placebo-controlled studies.

J Psychopharmacol 2021 Mar 30:269881121998322. Epub 2021 Mar 30.

Division of Clinical Pharmacology and Toxicology, University Hospital Basel, Basel, Switzerland.

Background: 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is used both recreationally and therapeutically. Little is known about the factors influencing inter- and intra-individual differences in the acute response to MDMA. Effects of other psychoactive substances have been shown to be critically influenced by personality traits and mood state before intake. Read More

View Article and Full-Text PDF

Biochip-based approach for comprehensive pharmacogenetic testing.

Drug Metab Pers Ther 2020 Dec 14. Epub 2020 Dec 14.

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.

Objectives: Individual sensitivity to many widely used drugs is significantly associated with genetic factors. The purpose of our work was to develop an instrument for simultaneous determination of the most clinically relevant pharmacogenetic markers to allow personalized treatment, mainly in patients with cardiovascular diseases.

Methods: Multiplex one-step polymerase chain reaction (PCR) followed by hybridization on a low-density biochip was applied to interrogate 15 polymorphisms in the following eight genes:  -1639 G>A 1297 G>A 2374 C>G *2,*3 (430 C>T, 1075 A>C) (2549delA, 1846 G>A, 1707delT, 2615_2617delAAG, 2988 G>A), (681 G>A, 636 G>A, -806 C>T) (3435 C>T). Read More

View Article and Full-Text PDF
December 2020

Urinary metabolites of non-persistent pesticides and serum hormones in Spanish adolescent males.

Environ Res 2021 Mar 23;197:111016. Epub 2021 Mar 23.

Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012, Granada, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Spain; Biomedical Research Center (CIBM), University of Granada, 18100, Granada, Spain; Department of Radiology and Physical Medicine, School of Medicine, University of Granada, 18071, Granada, Spain. Electronic address:

Objective: To assess the relationship of urinary concentrations of ethylenethiourea (ETU), the main degradation product of ethylene bis-dithiocarbamate fungicides, 3-phenoxybenzoic acid (3-PBA), a common metabolite of many pyrethroids, and 1-naphthol (1N), a metabolite of the carbamate insecticide carbaryl, with hormone concentrations in adolescent males; and to examine interactions between pesticide metabolites and polymorphisms in xenobiotic metabolizing enzymes, including CYP2C19 and CYP2D6, in relation to hormone concentrations.

Methods: A cross-sectional study was conducted in 134 males from the Spanish Environment and Childhood (INMA)-Granada cohort. Urine and serum samples were collected from participants during the same clinical visit at the age of 15-17 years. Read More

View Article and Full-Text PDF

CYP2D6 and CYP3A4 variants influence the risk and outcome of COVID-19 infection among rheumatoid arthritis patients maintained on hydroxychloroquine.

Drug Metab Pers Ther 2021 Mar 26. Epub 2021 Mar 26.

Department of Rheumatology and Rehabilitation, Assuit University, Assiut, Egypt.

Objectives: Hydroxychloroquine (HCQ) has been used as an off label for the management of coronavirus disease (Covid-19) infection with other drugs. However, different genetic variants can affect the metabolism of HCQ leading to inter-individual differences in its efficacy. In this study, we investigated the effects of variants in CYP2D6, CYP3A4 and CYP3A5 on the risk of Covid-19 infection among patients receiving HCQ for controlling rheumatoid arthritis (RA). Read More

View Article and Full-Text PDF

Association of CYP2D6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial.

NPJ Breast Cancer 2021 Mar 25;7(1):34. Epub 2021 Mar 25.

Department of Clinical Science, University of Bergen, Bergen, Norway.

Low-dose tamoxifen halves recurrence in non-invasive breast cancer without significant adverse events. Some adjuvant trials with tamoxifen 20 mg/day had shown an association between low endoxifen levels (9-16 nM) and recurrence, but no association with CYP2D6 was shown in the NSABP P1 and P2 prevention trials. We studied the association of CYP2D6 genotype and tamoxifen metabolites with tumor biomarkers and recurrence in a randomized phase III trial of low-dose tamoxifen. Read More

View Article and Full-Text PDF

Evidence for Pharmacogenomic Effects on Risperidone Outcomes in Pediatrics.

J Dev Behav Pediatr 2021 Apr;42(3):205-212

Departments of Pediatrics.

Objective: To determine the association between genetic variants reported to affect risperidone and adverse events (AEs) in children and adolescents.

Methods: Individuals aged 18 years or younger with ≥4 weeks of risperidone exposure in a deidentified DNA biobank were included. The primary outcome was AE frequency as a function of genotype. Read More

View Article and Full-Text PDF

Potentially actionable pharmacogenetic variants and symptom control medications in oncology.

Support Care Cancer 2021 Mar 24. Epub 2021 Mar 24.

Department of Supportive Oncology, Atrium Health Levine Cancer Institute, Charlotte, NC, USA.

Purpose: We estimated the prevalence of potentially actionable pharmacogenetic (PGx) variants related to symptom control medications (SCMs) based on institutional prescribing patterns and correlated presenting symptoms with SCM prescribing.

Methods: This was a retrospective study of adult ambulatory cancer patients undergoing electronic distress screening (EDS) within 90 days of intake to the cancer hospital. We estimated the proportion prescribed SCM(s) with PGx evidence within 90 days of intake. Read More

View Article and Full-Text PDF