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https://www.readbyqxmd.com/read/28931682/susceptibility-of-human-endogenous-retrovirus-type-k-to-reverse-transcriptase-inhibitors
#1
Rafael A Contreras-Galindo, Derek Dube, Koh Fujinaga, Mark H Kaplan, David M Markovitz
Human Endogenous Retroviruses make up 8% of the human genome. The HERV-K HML-2 (HK2) family contains proviruses that are the most recent entrants into the human germline and are transcriptionally active. In HIV-1 infection and cancer, HK2 genes produce retroviral particles that appear to be infectious, yet the replication capacity of these viruses and potential pathogenicity has been difficult to ascertain. In this report, we screened the efficacy of commercially available reverse transcriptase inhibitors (RTIs) at inhibiting the enzymatic activity of the HK2 RT and HK2 genomic replication...
September 20, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28927987/industry-perspective-on-contemporary-protein-binding-methodologies-considerations-for-regulatory-drug-drug-interaction-and-related-guidelines-on-highly-bound-drugs
#2
REVIEW
Li Di, Christopher Breen, Rob Chambers, Sean T Eckley, Robert Fricke, Avijit Ghosh, Paul Harradine, J Cory Kalvass, Stacy Ho, Caroline A Lee, Punit Marathe, Everett J Perkins, Mark Qian, Susanna Tse, Zhengyin Yan, Maciej J Zamek-Gliszczynski
Regulatory agencies have recently issued drug-drug interaction (DDI) guidelines, which require determination of plasma protein binding (PPB). To err on the conservative side, the agencies recommend that a 0.01 lower limit of fraction unbound (fu) be used for highly bound compounds (>99%), irrespective of the actual measured values. While this may avoid false negatives, the recommendation would likely result in a high rate of false positive predictions, resulting in unnecessary clinical studies and more stringent inclusion/exclusion criteria, which may add cost and time in delivery of new medicines to patients...
September 16, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28927497/decision-to-delivery-time-and-perinatal-complications-in-emergency-cesarean-section
#3
Günther Heller, Erik Bauer, Stefanie Schill, Teresa Thomas, Frank Louwen, Friedrich Wolff, Björn Misselwitz, Stephan Schmidt, Christof Veit
BACKGROUND: A decision-to-delivery interval (DDI) of no more than 20 minutes has long been considered a requirement for cesarean sections, even though there have hardly been any studies on this topic. We retrospectively investigated data relevant to DDI for emergency cesarean sections performed for the most common indications, namely, suspected and documented fetal asphyxia. METHODS: We analyzed data on emergency in-hospital cesarean sections in the period 2008-2015...
September 4, 2017: Deutsches Ärzteblatt International
https://www.readbyqxmd.com/read/28916286/toxicology-studies-of-primycin-sulphate-using-a-three-dimensional-3d-in-vitro-human-liver-aggregate-model
#4
Ágota Pénzes, Elhusseiny Mohamed Mahmud Abdelwahab, Judit Rapp, Zsanett A Péteri, Judit Bovári-Biri, Csaba Fekete, György Miskei, Krisztián Kvell, Judit E Pongrácz
Primycin-sulphate is a highly effective compound against Gram (G) positive bacteria. It has a potentially synergistic effect with vancomycin and statins which makes primycin-sulphate a potentially very effective preparation. Primycin-sulphate is currently used exclusively in topical preparations. In vitro animal hepatocyte and neuromuscular junction studies (in mice, rats, snakes, frogs) as well as in in vitro human red blood cell experiments were used to test toxicity. During these studies, the use of primycin-sulphate resulted in reduced cellular membrane integrity and modified ion channel activity...
September 13, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28912253/physiologically-based-pharmacokinetic-model-predictions-of-panobinostat-lbh589-as-a-victim-and-perpetrator-of-drug-drug-interactions
#5
Heidi J Einolf, Wen Lin, Christina S Won, Lai Wang, Helen Gu, Dung Yu Chun, Handan He, James B Mangold
Panobinostat (Farydak®) is an orally active hydroxamic acid derived histone deacetylase inhibitor for the treatment of relapsed/refractory multiple myeloma. Based upon recombinant cytochrome P450 (CYP) kinetic analyses in vitro, panobinostat oxidative metabolism in human liver microsomes was found to be primarily mediated by CYP3A4 with lower contributions by CYP2D6 and CYP2C19. Panobinostat was also shown to be an in vitro reversible and time-dependent inhibitor of CYP3A4/5, and a reversible inhibitor of CYP2D6 and CYP2C19...
September 14, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28910306/a-quantitative-systems-pharmacology-approach-incorporating-a-novel-liver-model-for-predicting-pharmacokinetic-drug-drug-interactions
#6
Mohammed H Cherkaoui-Rbati, Stuart W Paine, Peter Littlewood, Cyril Rauch
All pharmaceutical companies are required to assess pharmacokinetic drug-drug interactions (DDIs) of new chemical entities (NCEs) and mathematical prediction helps to select the best NCE candidate with regard to adverse effects resulting from a DDI before any costly clinical studies. Most current models assume that the liver is a homogeneous organ where the majority of the metabolism occurs. However, the circulatory system of the liver has a complex hierarchical geometry which distributes xenobiotics throughout the organ...
2017: PloS One
https://www.readbyqxmd.com/read/28906404/ticagrelor-induced-life-threatening-bleeding-via-the-cyclosporine-mediated-drug-interaction-a-case-report
#7
Chi Zhang, Long Shen, Min Cui, Xiaoyan Liu, Zhichun Gu
RATIONALE: Ticagrelor has become one of the first-line antiplatelet agents in acute coronary syndrome (ACS) patients recommend by the guideline due to its more potent and predictable antiplatelet effect. However, bleeding is still a severe drug adverse reaction of ticagrelor therapy. We report a first case on ticagrelor-induced life-threatening bleeding via the cyclosporine-mediated drug interaction. PATIENT CONCERNS: A 58-year-old Chinese male who received cyclosporine 200 mg daily 5 years after renal transplantation...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28905202/drug-interactions-in-users-of-tablet-vs-oral-liquid-levothyroxine-formulations-a-real-world-evidence-study-in-primary-care
#8
Valeria Guglielmi, Alfonso Bellia, Elisa Bianchini, Gerardo Medea, Iacopo Cricelli, Paolo Sbraccia, Davide Lauro, Claudio Cricelli, Francesco Lapi
PURPOSE: Several medications may interact with levothyroxine (LT4) intestinal absorption or metabolism, thus reducing its bioavailability. We investigated the variability of thyroid stimulating hormone (TSH) levels and prescribed daily dosages (PDDs) of LT4 before and during potential drug-drug interactions (DDIs) in users of tablets vs. oral liquid LT4 formulations. METHODS: By using the Italian general practice Health Search Database (HSD), we retrospectively selected adult patients with at least one LT4 prescription from 2012 to 2015 and at least 1 year of clinical history recorded...
September 14, 2017: Endocrine
https://www.readbyqxmd.com/read/28902678/brief-report-high-need-to-switch-cart-or-comedication-with-the-initiation-of-daas-in-elderly-hiv-hcv-coinfected-patients
#9
Elise J Smolders, Colette Smit, Clara T M M de Kanter, Anton S M Dofferiiof, Joop E Arends, Kees Brinkman, Bart Rijnders, Marc van der Valk, Peter Reiss, David M Burger
BACKGROUND: To describe the use of nonantiretroviral comedication and combination antiretroviral therapy (cART) in patients coinfected with HIV/hepatitis C virus (HCV) and to predict the potential for drug-drug interactions (DDIs) with direct-acting antivirals (DAAs) against HCV. METHODS: This is a retrospective, cross-sectional study, using the Dutch, nationwide ATHENA observational HIV cohort database. All patients with a known HIV/HCV coinfection on January 1, 2015, were included...
October 1, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28895028/prevalence-of-qt-interval-prolonging-drug-drug-interactions-qt-ddis-in-psychiatry-wards-of-tertiary-care-hospitals-in-pakistan-a-multicenter-cross-sectional-study
#10
Qasim Khan, Mohammad Ismail, Iqbal Haider, Fahadullah Khan
Background QT prolongation and associated arrhythmias, torsades de pointes (TdP), are considerable negative outcomes of many antipsychotic and antidepressant agents frequently used by psychiatric patients. Objective To identify the prevalence, levels, and predictors of QT prolonging drug-drug interactions (QT-DDIs), and AZCERT (Arizona Center for Education and Research on Therapeutics) classification of drugs involved in QT-DDIs. Setting Psychiatry wards of three major tertiary care hospitals of Khyber-Pakhtunkhwa, Pakistan...
September 12, 2017: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/28892271/potential-drug-drug-interactions-and-polypharmacy-in-institutionalized-elderly-patients-in-a-public-hospital-in-brazil
#11
Ellen Carolina Dias Castilho, Adriano Max Moreira Reis, Tatiana Longo Borges, Lilian Dias Castilho Siqueira, Adriana Inocenti Miasso
INTRODUCTION: Despite the impact on patient safety and the fact that prevalence is higher in older patients, previous research did not analyse drug-drug interactions (DDIs) in view of nursing care of elderly psychiatric patients. AIM: To identify potential drug-drug interactions and polypharmacy in prescriptions of aged inpatients with psychiatric disorders and analyse associated factors. METHODS: In this retrospective cross-sectional study, we analysed the medical records of institutionalized patients diagnosed with psychiatric disorders (n = 94), aged >60 years, and prescribed multiple medications...
September 11, 2017: Journal of Psychiatric and Mental Health Nursing
https://www.readbyqxmd.com/read/28881501/drug-drug-interaction-potential-in-men-treated-with-enzalutamide-mind-the-gap
#12
G E Benoist, I M van Oort, S Smeenk, A Javad, D M Somford, D M Burger, N Mehra, N P van Erp
AIM: Metastatic castration resistant prostate cancer (mCRPC) patients are generally older patients with several co-morbidities and are therefore more at risk for complications due to drug-drug interactions(DDIs). We assessed the prevalence of potential DDIs in a cohort of mCRPC patients treated with enzalutamide. METHODS: We conducted a retrospective review of pharmacy records to retrieve individual drug histories of mCRPC patients who started enzalutamide therapy in a tertiary care setting...
September 7, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28876170/transgender-women-living-with-hiv-frequently-take-antiretroviral-therapy-and-or-feminizing-hormone-therapy-differently-than-prescribed-due-to-drug-drug-interaction-concerns
#13
Hannan M Braun, Jury Candelario, Courtney L Hanlon, Eddy R Segura, Jesse L Clark, Judith S Currier, Jordan E Lake
PURPOSE: Both hormone therapy (HT) and antiretroviral therapy (ART) can be lifesaving for transgender women (TW) living with HIV, but each has side effects and potential drug-drug interactions (DDI). We assessed how concerns about HT-ART interactions affect treatment adherence. METHODS: This study used a cross-sectional survey of TW (n = 87) in Los Angeles, CA. RESULTS: Fifty-four percent were living with HIV; 64% used HT. Only 49% of TW living with HIV discussed ART-HT DDI with their provider; 40% reported not taking ART (12%), HT (12%), or both (16%) as directed due to DDI concerns...
September 6, 2017: LGBT Health
https://www.readbyqxmd.com/read/28869702/the-prevalence-and-preventability-of-potentially-relevant-drug-drug-interactions-in-patients-admitted-for-cardiovascular-diseases-a-cross-sectional-study
#14
Milena Kovačević, Sandra Vezmar Kovačević, Branislava Miljković, Slavica Radovanović, Predrag Stevanović
AIM: The aim was to describe the type and prevalence of potentially relevant drug-drug interactions (pDDIs) in a population of patients admitted for cardiovascular diseases (CVD), and management strategies for reducing the occurrence of pDDIs. METHODS: A retrospective cross-sectional study was performed on Cardiology ward of University Clinical Hospital Center in Belgrade, Serbia. A total of 527 patients, with more than one prescription during hospital stay, were enrolled in this study...
September 4, 2017: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28867436/effects-of-diosmetin-on-nine-cytochrome-p450-isoforms-ugts-and-three-drug-transporters-in-vitro
#15
Jun-Jun Chen, Jing-Xian Zhang, Xiang-Qi Zhang, Mei-Juan Qi, Mei-Zhi Shi, Jiao Yang, Ke-Zhi Zhang, Cheng Guo, Yong-Long Han
Diosmetin (3', 5, 7-trihydroxy-4'-methoxyflavone), a natural flavonoid from traditional Chinese herbs, has been used in various medicinal products because of its anticancer, antimicrobial, antioxidant, estrogenic and anti-inflammatory activity. However, flavonoids could affect the metabolic enzymes and cause drug-drug interactions (DDI), reducing the efficacy of co-administered drugs and potentially resulting in serious adverse reactions. To evaluate its potential to interact with co-administered drugs, the IC50 value of phase I cytochrome P450 enzymes (CYPs), phase II UDP-glucuronyltransferases (UGTs) and hepatic uptake transporters (organic cation transporters (OCTs), organic anion transporter polypeptides (OATPs) and Na(+)-taurocholate cotransporting polypeptides (NTCPs)) were examined in vitro by LC-MS/MS...
September 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28860861/potential-drug-drug-interactions-in-inpatients-treated-at-the-internal-medicine-ward-of-tikur-anbessa-specialized-hospital
#16
Zelalem Tilahun Tesfaye, Teshome Nedi
PURPOSE: Although the concomitant use of multiple drugs often increases therapeutic effectiveness, certain combinations result in unwanted drug-drug interactions (DDIs). Most interactions go unnoticed by physicians due to the absence of new clinical signs and symptoms, and because they often produce a worsening of already existing symptoms. Quantification of the occurrence of the potential DDIs is essential to prevent the harmful effects associated with interactions. This study was launched to assess the prevalence of potential DDIs in the Internal Medicine ward of Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia...
2017: Drug, Healthcare and Patient Safety
https://www.readbyqxmd.com/read/28860113/physiologically-based-pharmacokinetic-pbpk-model-of-the-cyp2d6-probe-atomoxetine-extrapolation-to-special-populations-and-drug-drug-interactions
#17
Weize Huang, Mariko Nakano, Jennifer E Sager, Isabelle Ragueneau-Majlessi, Nina Isoherranen
Physiologically based pharmacokinetic (PBPK) modeling of drug disposition and drug-drug interactions has become a key component of drug development. PBPK modeling has also been considered as an approach to predict drug disposition in special populations. However, whether models developed and validated in healthy populations can be extrapolated to special populations is not well established. The goal of this study was to determine whether a drug specific PBPK model validated using healthy populations could be used to predict drug disposition in specific populations and in organ impairment...
August 31, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28851511/polypharmacy-potentially-inappropriate-medications-and-drug-drug-interactions-in-geriatric-patients-with-hematologic-malignancy-observational-single-center-study-of-122-patients
#18
David Y Leger, Stephane Moreau, Nicolas Signol, Jean-Baptiste Fargeas, Marie-Agnès Picat, Amélie Penot, Julie Abraham, Marie-Laure Laroche, Dominique Bordessoule
OBJECTIVES: Geriatric patients with hematologic malignancies (HMs) are prescribed targeted and supportive care treatments that add to the preexisting polypharmacy (PP). PP is associated with an increased risk of potentially inappropriate medications (PIM) and drug-drug interactions (DDI) resulting in increased hospitalization and mortality in the elderly. As very few data exist on these medication issues in the context of HMs, the objective of this study was to evaluate prevalence of PP, DDI and PIM use at baseline and 3months among elderly patients with HMs who received baseline geriatric assessment...
August 26, 2017: Journal of Geriatric Oncology
https://www.readbyqxmd.com/read/28851254/quantitative-prediction-of-the-extent-of-drug-drug-interaction-using-a-physiologically-based-pharmacokinetic-model-that-includes-inhibition-of-drug-metabolism-determined-in-cryopreserved-hepatocytes
#19
Shinji Iwasaki, Hideki Hirabayashi, Nobuyuki Amano
1. A physiologically based pharmacokinetic (PBPK) model that includes inhibition constant evaluated in cryopreserved hepatocytes was used to predict drug-drug interactions (DDIs) between orally administered nifedipine, a CYP substrate, and fluconazole or ketoconazole, CYP inhibitors, in rats. 2. The Kp,uu, ratio of unbound inhibitor concentration in liver ([I]liver,u) to that in plasma ([I]sys,u), of fluconazole and ketoconazole was 1.0 and 13.0, indicating that ketoconazole accumulates in liver. The ratios of inhibition constants in rat liver microsomes (Ki,mic,u) to that in rat cryopreserved hepatocytes (Ki,hep,u) for fluconazole and ketoconazole were 1...
September 4, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28845110/prioritization-for-interferon-free-regimens-and-potential-drug-interactions-of-current-direct-acting-anti-hepatitis-c-agents-in-routine-clinical-practice
#20
Μargarita Papatheodoridi, George N Dalekos, John Goulis, Spilios Manolakopoulos, Christos Triantos, Kalliopi Zachou, Argyro Koukoufiki, Αnastasia Κourikou, Κonstantinos Ζisimopoulos, Christos Τsoulas, George V Papatheodoridis
BACKGROUND: We determined the proportions of patients with chronic hepatitis C (CHC) in association with possible prioritized indications for interferon-free regimens and the use of co-medications with potential drug-drug interactions (DDIs). METHODS: Five hundred consecutive mono-infected CHC patients seen in 2015 at 5 Greek centers were included. Priorities for interferon-free regimens were based on liver disease severity, contraindication(s) for interferon and prior interferon-treatment failure...
2017: Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology
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