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Expert Opinion on Drug Metabolism & Toxicology

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https://www.readbyqxmd.com/read/27927043/allopurinol-insights-from-studies-of-dose-response-relationships
#1
Richard O Day, Diluk R W Kannangara, Sophie L Stocker, Jane E Carland, Kenneth M Williams, Garry G Graham
Gout is the most common inflammatory arthritis in men and is increasingly prevalent. Allopurinol is very effective at reducing plasma urate concentrations to a level sufficient to dissolve monosodium urate crystals. However, many patients fail to achieve a sufficient therapeutic response to allopurinol. Areas covered: This review covers the metabolism and pharmacokinetics of allopurinol and its active metabolite, oxypurinol and how these factors affect the plasma concentrations of urate at initiation and during long-term therapy with allopurinol...
December 7, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27817207/evaluation-of-the-pharmacokinetics-pharmacodynamics-and-clinical-efficacy-of-empagliflozin-for-the-treatment-of-type-2-diabetes
#2
Brian Tomlinson, Miao Hu, Yuzhen Zhang, Paul Chan, Zhong-Min Liu
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are the latest class of drugs to be introduced for the treatment of type 2 diabetes mellitus. These drugs improve glycemic control by increasing urinary glucose excretion and exert additional benefits of weight loss and blood pressure reductions. Areas covered: This review outlines the background to SGLT2 inhibitors and provides details on the pharmacokinetics, pharmacodynamics and clinical efficacy of empagliflozin and discusses the cardiovascular outcome trial...
November 20, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27860490/pharmacoepigenetics-an-element-of-personalized-therapy
#3
Aleksandra Majchrzak-Celińska, Wanda Baer-Dubowska
Epigenetics is a rapidly growing field describing heritable alterations in gene expression that do not involve DNA sequence variations. Advances in epigenetics and epigenomics have influenced pharmacology, leading to the development of a new specialty, pharmacoepigenetics, the study of the epigenetic basis for the individual variation in drug response. Areas covered: We present an overview of the major epigenetic mechanisms and their effects on the expression of drug-metabolizing enzymes and drug transporters, as well as thr epigenetic status of drug protein targets affecting therapy response...
November 18, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27860485/an-update-on-the-use-of-benzoate-phenylacetate-and-phenylbutyrate-ammonia-scavengers-for-interrogating-and-modifying-liver-nitrogen-metabolism-and-its-implications-in-urea-cycle-disorders-and-liver-disease
#4
Javier de Las Heras, Luis Aldámiz-Echevarría, María-Luz Martínez-Chantar, Teresa C Delgado
Ammonia-scavenging drugs, benzoate and phenylacetate (PA)/phenylbutyrate (PB), modulate hepatic nitrogen metabolism mainly by providing alternative pathways for nitrogen disposal. Areas Covered: We review the major findings and potential novel applications of ammonia-scavenging drugs, focusing on urea cycle disorders and liver disease. Expert Opinion: For over 40 years, ammonia-scavenging drugs have been used in the treatment of urea cycle disorders. Recently, the use of these compounds has been advocated in acute liver failure and cirrhosis for reducing hyperammonemic-induced hepatic encephalopathy...
November 18, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27852117/pharmacokinetic-drug-evaluation-of-anacetrapib-for-the-treatment-of-dyslipidemia
#5
Claudio Borghi, Arrigo F G Cicero
While some cholesteryl ester transfer protein inhibitors have had their clinical study interrupted because of no or adverse effects on cardiovascular disease, anacetrapib (MK-0859) is being evaluated in Phase III cardiovascular outcomes trials. We review its pharmacokinetic properties. Areas covered: The apparent anacetrapib terminal elimination half-life after a single dose is 9-62 hours in the fasted state and 42-83 hours in the fed state. After repeat administrations, a biphasic elimination profile with a long terminal elimination phase (~60-80 h) was observed, although the effective half-life was ~20 h...
November 17, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27819147/chemotherapy-induced-peripheral-neurotoxicity-outcome-measures-the-issue
#6
Paola Alberti
No abstract text is available yet for this article.
November 17, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27819144/effects-of-sodium-glucose-co-transporter-2-inhibitors-on-metabolism-unanswered-questions-and-controversies
#7
Vasilios Tsimihodimos, Theodosios D Filippatos, Moses S Elisaf
Sodium-glucose co-transporter 2 (SGLT2) inhibitors inhibit glucose re-absorption in the proximal renal tubules. These drugs also affect many anthropometric and metabolic parameters with various mechanisms of action. Areas covered: We present the available evidence regarding these effects. SGLT2 inhibitors can decrease body weight mainly due to a reduction of total fat mass. SGLT2 inhibitors can decrease blood pressure levels and serum uric acid levels and may also reduce the degree of diabetes-related albuminuria...
November 17, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27822971/drug-induced-liver-injury-is-chronic-liver-disease-a-risk-factor-and-a-clinical-issue
#8
Rolf Teschke, Gaby Danan
Clinicians and practitioners caring for patients with chronic liver disease are often unsure whether drug therapy is a hazard that increases their patient's risk for drug-induced liver injury (DILI). Areas covered: We searched for reports of drug induced liver injury, both idiosyncratic and intrinsic, in patients with chronic liver disease including non-alcoholic and alcoholic liver disease, and cirrhosis. Reports we analyzed include statin treatment in patients with fatty liver, acetaminophen use in alcoholic fatty liver, antituberculous drugs in patients with tuberculosis and viral hepatitis, antiviral medications in hepatitis and antiretroviral medications in HIV/AIDS...
November 8, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27776453/individualized-patient-centered-use-of-lixisenatide-for-the-treatment-of-type-2-diabetes-mellitus
#9
Markolf Hanefeld, Denis Raccah, Louis Monnier
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease associated with hyperglycemia, which can lead to serious vascular complications. Current treatment guidelines place particular emphasis on personalization of therapy. Within this guidance, the use of various second-line therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), is recommended under certain circumstances. Areas covered: Factors influencing glucose homeostasis, including gastric emptying and the associated cardiovascular (CV) risk when homeostasis is not maintained, are reviewed...
November 3, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27766914/n-acetylcysteine-in-the-treatment-of-psychiatric-disorders-current-status-and-future-prospects
#10
Alessandro Minarini, Silvia Ferrari, Martina Galletti, Nina Giambalvo, Daniela Perrone, Giulia Rioli, Gian Maria Galeazzi
N-acetylcysteine (NAC) is widely known for its role as a mucolytic and as an antidote to paracetamol overdose. There is increasing interest in the use of NAC in the treatment of several psychiatric disorders. The rationale for the administration of NAC in psychiatric conditions is based on its role as a precursor to the antioxidant glutathione, and its action as a modulating agent of glutamatergic, dopaminergic, neurotropic and inflammatory pathways. Areas covered: This study reviews the available data regarding the use of NAC in different psychiatric disorders including substance use disorders, autism, obsessive-compulsive spectrum disorders, schizophrenia, depression, bipolar disorder...
November 2, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27764576/multidrug-efflux-pumps-and-their-role-in-antibiotic-and-antiseptic-resistance-a-pharmacodynamic-perspective
#11
Sandrine Alibert, Joannah N'gompaza Diarra, Jessica Hernandez, Aurélien Stutzmann, Marwa Fouad, Gérard Boyer, Jean-Marie Pagès
Worrying levels of bacterial resistance have been reported worldwide involving the failure of many available antibiotic treatments. Multidrug resistance (MDR) in Gram-negative bacteria is often ascribed to the presence of multiple and different resistance mechanisms in the same strain. RND efflux pumps play a major role and are an attractive target to discover new antibacterial drugs. Areas covered: This review discusses the prevalence of efflux pumps, their overexpression in clinical scenarios, their polyselectivity, their effect on the intracellular concentrations of various antibiotics associated with the alteration of the membrane permeability and their involvement in pathogenicity are discussed...
November 2, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27783531/the-role-of-organic-anion-transporting-polypeptides-in-drug-absorption-distribution-excretion-and-drug-drug-interactions
#12
Daniella Kovacsics, Izabel Patik, Csilla Özvegy-Laczka
The in vivo fate and effectiveness of a drug depends highly on its absorption, distribution, metabolism, excretion and toxicity (ADME-Tox). Organic anion transporting polypeptides (OATPs) are membrane proteins involved in the cellular uptake of various organic compounds, including clinically used drugs. Since OATPs are significant players in drug absorption and distribution, modulation of OATP function via pharmacotherapy with OATP substrates/inhibitors, or modulation of their expression, affects drug pharmacokinetics...
October 26, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27766890/pharmacokinetic-properties-and-drug-interactions-of-apigenin-a-natural-flavone
#13
Ding Tang, Keli Chen, Luqi Huang, Juan Li
Apigenin, a natural flavone, is widely distributed in plants such as celery, parsley and chamomile. It is present principally as glycosylated in nature. Higher intake of apigenin could reduce the risk of chronic diseases. It has gained particular interest in recent years as a beneficial, health-promoting agent with low intrinsic toxicity. Areas covered: This review summarizes and the absorption, distribution, metabolism and excretion (ADME) properties of apigenin, and drug-drug interaction of apigenin. Expert opinion: Since apigenin is a bioactive plant flavone and is widely distributed in common food, its consumption through the diet is recommended...
October 21, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27759439/drug-induced-steatohepatitis
#14
Ajit Dash, Robert A Figler, Arun J Sanyal, B R Wamhoff
Drug induced steatohepatitis (DISH), a form of drug induced liver injury (DILI) is characterized by intracellular accumulation of lipids in hepatocytes and subsequent inflammatory events, in some ways similar to the pathology seen with other metabolic, viral and genetic causes of non alcoholic fatty liver disease and steatohepatitis (NAFLD and NASH). Areas covered: This paper provides a comprehensive review of the main underlying mechanisms by which various drugs cause DISH, and outlines existing preclinical tools to predict it and study underlying pathways involved...
October 19, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27759434/drug-induced-eruptive-melanocytic-nevi
#15
Gino A Vena, Maria Concetta Fargnoli, Nicoletta Cassano, Giuseppe Argenziano
The sudden eruption of melanocytic nevi has been associated with a number of conditions, such as bullous skin diseases, immunodeficiency and immunosuppression. The exact mechanisms leading to the development of eruptive melanocytic nevi are unknown. Areas covered: The aim of this article is to review the literature concerning eruptive melanocytic nevi following the administration of immunosuppressive drugs and other medications. Expert opinion: The literature regarding the development of eruptive nevi in association with pharmacological therapies includes a relatively low number of reports...
October 19, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27758143/pharmacogenomics-of-genes-involved-in-antifolate-drug-response-and-toxicity-in-osteosarcoma
#16
Claudia Maria Hattinger, Elisa Tavanti, Marilù Fanelli, Serena Vella, Piero Picci, Massimo Serra
Antifolates are structural analogs of folates, which have been used as antitumor drugs for more than 60 years. The antifolate drug most commonly used for treating human tumors is methotrexate (MTX), which is utilized widely in first-line treatment protocols of high-grade osteosarcoma (HGOS). In addition to MTX, two other antifolates, trimetrexate and pemetrexed, have been tested in clinical settings for second-line treatment of recurrent HGOS with patients unfortunately showing modest activity. Areas covered: There is clinical evidence which suggsest that, like other chemotherapeutic agents, not all HGOS patients are equally responsive to antifolates and do not have the same susceptibility to experience adverse drug-related toxicities...
October 19, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27686109/pharmacokinetic-and-pharmacodynamic-evaluation-of-ibrutinib-for-the-treatment-of-chronic-lymphocytic-leukemia-rationale-for-lower-doses
#17
Prithviraj Bose, Varsha V Gandhi, Michael J Keating
Ibrutinib, a first-in-class covalent inhibitor of Bruton's tyrosine kinase (BTK), is approved in many countries for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL) and for previously untreated disease with a 17p deletion and, most recently, as a frontline therapy for CLL. In controlled trials in CLL, ibrutinib produced high response rates and improved survival in both the frontline and relapsed settings. While ibrutinib controls CLL with impressive efficacy, it only infrequently induces complete remissions, particularly of relapsed CLL, and does not eradicate minimal residual disease...
October 11, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27724053/judging-the-value-of-liver-on-a-chip-devices-for-prediction-of-toxicity
#18
Viktoriia Starokozhko, Geny M M Groothuis
No abstract text is available yet for this article.
October 10, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27718745/pharmacogenetics-of-neurological-and-psychiatric-diseases-at-older-age-has-the-time-come
#19
Madia Lozupone, Francesco Panza, Eleonora Stella, Maddalena La Montagna, Paola Bisceglia, Giuseppe Miscio, Ilaria Galizia, Antonio Daniele, Lazzaro di Mauro, Antonello Bellomo, Giancarlo Logroscino, Antonio Greco, Davide Seripa
In recent years, a number of pharmacological approaches for treating neuropsychiatric conditions at older age have proven to be inadequate. The resulting increased prevalence of therapeutic failures (TF) and a worsening of clinical symptoms often linked to adverse reactions (ADRs), are perhaps among the major causes of the increasing rate of hospitalizations and institutionalizations observed in these patients. Areas covered: This review underlines the importance of pharmacogenetic data to fingerprint the pharmacological treatment of neuropsychiatric late-life conditions throughout the analysis of metabolizing enzymes and transporters of psychotropic drugs, mainly those of the cytochrome P450 (CYP) family...
October 8, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27696906/the-role-of-fulvestrant-in-endometrial-cancer
#20
Stefano Bogliolo, Chiara Cassani, Mattia Dominoni, Anna Orlandini, Simone Ferrero, Anna Daniela Iacobone, Franco Viazzo, Pier Luigi Venturini, Arsenio Spinillo, Barbara Gardella
Endometrial cancer is the most common malignancy of the female genital tract in industrialized countries. The traditional treatment of endometrial cancer is based on a surgical approach. In recent years, systemic endocrine therapy has demonstrated good efficacy in recurrent or metastatic setting, delaying progression, ameliorating quality of life and palliating symptoms. Areas covered: Phase I and II studies on selective estrogen receptor down-regulators used for the treatment of endometrial cancer treatment have been reviewed...
October 4, 2016: Expert Opinion on Drug Metabolism & Toxicology
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