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Expert Opinion on Drug Metabolism & Toxicology

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https://www.readbyqxmd.com/read/28075650/pharmacokinetic-evaluation-of-pregabalin-for-the-treatment-of-generalized-anxiety-disorder
#1
Massimiliano Buoli, Alice Caldiroli, Marta Serati
Pregabalin is an alternative compound to SSRIs and SNRIs for the first-line treatment of generalized anxiety disorder (GAD). Areas covered: We describe the pharmacokinetic properties of pregabalin and their implications for the treatment of GAD. A search in the main database sources (Medline, ISI, Web of Knowledge and Medscape) was performed in order to obtain a comprehensive and balanced evaluation about the clinical implications of the pharmacokinetic properties of pregabalin in the treatment of GAD. The word "pregabalin" was associated with "pharmacokinetics", "interactions"', "GAD", "anxiety" and "tolerability"...
January 11, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28043170/impact-of-disease-drug-and-patient-adherence-on-the-effectiveness-of-antiviral-therapy-in-pediatric-hiv
#2
Chiara Piana, Meindert Danhof, Oscar Della Pasqua
Maintaining effective antiretroviral treatment for life is a major problem, in both resource-limited and resource-rich countries. Despite the progress observed in paediatric antiretroviral therapy, approximately 12% of children still experience treatment failure due to drug resistance, inadequate dosing and poor adherence. We explore the current status of antiretroviral therapy in children with focus on the interaction between disease, drug pharmacokinetics and patient behavior, all of which are strongly interconnected and determine treatment outcome...
January 3, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28019118/the-mechanisms-of-cyclophosphamide-induced-testicular-toxicity-and-the-protective-agents
#3
Emad Ghobadi, Milad Moloudizargari, Mohammad Hossein Asghari, Mohammad Abdollahi
Cyclophosphamide (CP) is an alkylating antineoplastic agent with known toxicity to the male reproductive system. Areas covered: This review summarizes the known mechanisms by which CP exerts its toxic effects on the male reproductive system and the methods utilized to prevent such effects so that it could be further investigated and applied in clinical use. Keywords including ['Cyclophosphamide' AND 'male reproductive' OR' sperm toxicity' OR 'spermatotoxicity' OR 'infertility] were searched through Google Scholar, PubMed and Scopus databases based on PRISMA guidelines...
December 29, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27927043/allopurinol-insights-from-studies-of-dose-response-relationships
#4
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 20, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27936967/potential-roles-of-myeloperoxidase-and-hypochlorous-acid-in-metabolism-and-toxicity-of-alkene-hydrocarbons-and-drug-molecules-containing-olefinic-moieties
#5
Xin-Yu Zhang, Adnan A Elfarra
Adverse drug reactions (ADRs) pose a significant health problem and are generally attributed to reactive metabolites. Olefinic moieties in drugs can undergo cytochrome P450-mediated bioactivation to produce reactive metabolites but myeloperoxidase (MPO)-mediated bioactivation of these moieties has not been reported. Thus, small molecules of alkene hydrocarbons are used as model compounds to characterize the MPO-mediated metabolism. Areas covered: The authors focus on MPO-mediated metabolism of alkene hydrocarbons to form chlorohydrins and the potential role of chlorohydrins in alkene toxicity and carcinogenicity...
December 16, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27860490/pharmacoepigenetics-an-element-of-personalized-therapy
#6
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
#7
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/27819147/chemotherapy-induced-peripheral-neurotoxicity-outcome-measures-the-issue
#8
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
#9
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
#10
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-centred-use-of-lixisenatide-for-the-treatment-of-type-2-diabetes-mellitus
#11
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...
October 25, 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
#12
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
#13
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
#14
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/28043166/pharmacokinetic-drug-evaluation-of-atezolizumab-for-the-treatment-of-locally-advanced-or-metastatic-urothelial-carcinoma
#15
Rutveej Patel, Megan Bock, Charles F Polotti, Sammy Elsamra
Muscle invasive bladder cancer (MIBC) is difficult to manage for patients who progress during or after initial chemotherapy regimens. Current regimens offer low response rates with high toxicities. The advent of immune checkpoint inhibitors may represent a new opportunity for effective management of these patients. Areas covered: Atezolizumab is an engineered humanized monoclonal immunoglobulin G1 antibody that binds selectively to PD-L1 and prevents its interaction with PD-1 and B7-1. It is administered intravenously and is given every 3 weeks as long as there is no evidence of tumor progression...
February 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27998194/use-of-monoamine-oxidase-inhibitors-in-chronic-neurodegeneration
#16
Peter Riederer, Thomas Müller
Neurotransmission by biogenic monoamines is important for brain function. Biogenic amine turnover employs the enzymes catechol-O-methyltransferase and monoamine oxidase in neuronal and glial cells. Inhibition of these enzymes elevates biogenic amine levels in the synaptic cleft. Subtype selectivity of inhibition is lost during long-term use of 'selective' monoamine oxidase inhibitors. Areas covered: This narrative review discusses use of monoamine oxidase inhibitors in the context with chronic neurodegeneration...
February 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27852117/pharmacokinetic-drug-evaluation-of-anacetrapib-for-the-treatment-of-dyslipidemia
#17
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 h in the fasted state and 42-83 h 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...
February 2017: 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
#18
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...
February 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27759439/drug-induced-steatohepatitis
#19
Ajit Dash, Robert A Figler, Arun J Sanyal, Brian 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...
February 2017: 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
#20
Viktoriia Starokozhko, Geny M M Groothuis
No abstract text is available yet for this article.
February 2017: Expert Opinion on Drug Metabolism & Toxicology
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