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https://www.readbyqxmd.com/read/28334805/hair-testing-for-drugs-of-abuse-and-new-psychoactive-substances-in-a-high-risk-population
#1
Alberto Salomone, Joseph J Palamar, Enrico Gerace, Daniele Di Corcia, Marco Vincenti
Hundreds of new psychoactive substances (NPS) have emerged in the drug market over the last decade. Few drug surveys in the USA, however, ask about use of NPS, so prevalence and correlates of use are largely unknown. A large portion of NPS use is unintentional or unknown as NPS are common adulterants in drugs like ecstasy/Molly, and most NPS are rapidly eliminated from the body, limiting efficacy of urine, blood and saliva testing. We utilized a novel method of examining prevalence of NPS use in a high-risk population utilizing hair-testing...
March 4, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28334528/why-prodrugs-and-propesticides-succeed
#2
John E Casida
What are the advantages of bioactivation in optimizing drugs and pesticides? Why are there so many prodrugs and propesticides? These questions are examined here by considering compounds selected on the basis of economic value or market success. The 100 major drugs and 90 major pesticides are divided into ones acting directly and those definitely or possibly requiring bioactivation. Established or candidate prodrugs accounted for 19% of the total drug sales with corresponding values of 20, 37 and 17% for proinsecticides, proherbicides and profungicides...
March 23, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28334417/pharmacovigilance-database-search-discloses-clc-k-channels-as-a-novel-target-of-the-at1-receptor-blockers-valsartan-and-olmesartan
#3
Paola Imbrici, Domenico Tricarico, Giuseppe Felice Mangiatordi, Orazio Nicolotti, Marcello Diego Lograno, Diana Conte, Antonella Liantonio
BACKGROUND AND PURPOSE: Human ClC-K chloride channels are highly attractive targets for drug discovery for their physiological role and association with genetic disorders. These channels are pivotal in the kidney as they control chloride reabsorption and water diuresis. In addition, loss-of-function mutations of CLCKNB and BSND genes cause Bartter's syndrome (BS), whereas CLCNKA and CLCKNB gain-of-function polymorphisms predispose to a rare form of salt sensitive hypertension. Both disorders lack a personalized therapy that is in most cases only symptomatic...
March 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28333231/tolerability-of-integrase-inhibitors-in-a-real-life-setting
#4
Judit Peñafiel, Elisa de Lazzari, Mireia Padilla, Jhon Rojas, Ana Gonzalez-Cordon, Jose L Blanco, Jordi Blanch, Maria A Marcos, Montserrat Lonca, Maria Martinez-Rebollar, Montserrat Laguno, Amparo Tricas, Ana Rodriguez, Josep Mallolas, Jose M Gatell, Esteban Martinez
Background: Integrase inhibitors have shown better tolerability than other drugs in clinical trials, but some post-marketing data have suggested potential differences among them. Aims: We compared rates and reasons for discontinuation of raltegravir-, elvitegravir- and dolutegravir-based regimens in a large cohort of HIV-infected patients. Methods: Retrospective analysis of a prospectively followed cohort including all antiretroviral-naive and all virologically suppressed antiretroviral-experienced patients prescribed a first regimen containing raltegravir, elvitegravir or dolutegravir with at least one follow-up visit...
February 28, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28333214/-forever-young-%C3%A2-testosterone-replacement-therapy-a-blockbuster-drug-despite-flabby-evidence-and-broken-promises
#5
Andrea Busnelli, Edgardo Somigliana, Paolo Vercellini
In the last decade, testosterone replacement therapy (TRT) has been increasingly prescribed to treat a controversial condition known as 'late-onset hypogonadism (LOH)'. This syndrome is diagnosed in men who, for no discernible reason other than older age, obesity or ill health have serum testosterone concentrations below the normal range for healthy young men and report one or more of the following symptoms: muscle weakness or wasting, mood, behaviour and cognition-related symptoms and sexual function or libido impairment...
February 23, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28332451/inhibitory-effect-of-fruit-juices-on-the-doxorubicin-metabolizing-activity-of-carbonyl-reductase-1
#6
Takeshi Miura, Katsutoshi Nagai, Shingo Kaneshiro, Ayako Taketomi, Toshikatsu Nakabayashi, Hiroki Konishi, Toru Nishinaka, Tomoyuki Terada
BACKGROUND AND OBJECTIVE: Doxorubicin, an anthracycline anti-cancer drug, is effective for breast cancer and childhood lymphoma. Chronic cardiotoxicity has been known as a critical adverse effect of doxorubicin and is attributed to its metabolite doxorubicinol produced by carbonyl reductase 1 (CBR1, SDR21C1). Some flavonoids have been reported to act as inhibitors for CBR1, therefore, commercially available juices containing flavonoids are likely to be applicable as a prophylactic treatment against doxorubicin-induced cardiotoxicity by suppression doxorubicinol production...
March 9, 2017: Drug Metabolism Letters
https://www.readbyqxmd.com/read/28331624/comparison-of-hydroxyethyl-starch-regulatory-summaries-from-the-food-and-drug-administration-and-the-european-medicines-agency
#7
Christian J Wiedermann, Klaus Eisendle
This article aims to highlight the positions of the Food and Drug Administration and the European Medicines Agency regarding use and marketing of hydroxyethyl starch (HES) products, and how these have changed over recent years. In 2013, warnings from both agencies advised against use of HES in critically ill patients, including patients with sepsis, when several large randomized controlled trials on volume resuscitation in critical illness failed to observe clinically beneficial effects of HES. In areas such as patient monitoring and requirements for further clinical trials, the FDA and EMA are very much in agreement in their recommendations...
2017: Journal of Pharmaceutical Policy and Practice
https://www.readbyqxmd.com/read/28331610/a-reappraisal-of-the-mucoactive-activity-and-clinical-efficacy-of-bromhexine
#8
REVIEW
Alessandro Zanasi, Massimiliano Mazzolini, Ahmad Kantar
Since its introduction to the market in 1963, bromhexine, an over-the-counter drug, has been investigated for its activity in animal models and in humans with diverse respiratory conditions. Bromhexine is a derivate of the Adhatoda vasica plant used in some countries for the treatment of various respiratory diseases. Bromhexine has been found to enhance the secretion of various mucus components by modifying the physicochemical characteristics of mucus. These changes, in turn, increase mucociliary clearance and reduce cough...
2017: Multidisciplinary Respiratory Medicine
https://www.readbyqxmd.com/read/28331539/randomized-placebo-controlled-phase-iv-pilot-study-of-ramosetron-to-evaluate-the-co-primary-end-points-in-male-patients-with-irritable-bowel-syndrome-with-diarrhea
#9
Motoko Ida, Akito Nishida, Hiraku Akiho, Yoshihiro Nakashima, Kei Matsueda, Shin Fukudo
BACKGROUND: Global assessment allows patients to assess improvement in multiple irritable bowel syndrome (IBS) symptoms. However, it was deemed important to assess "clinically meaningful improvements, focusing on the patient's chief complaint and the severity of major IBS symptoms" in addition to global assessment to show how ramosetron is effective for individual IBS symptoms. This is a pilot study to explore clinical endpoints focusing on the chief complaint of patients with IBS with diarrhea (IBS-D)...
2017: BioPsychoSocial Medicine
https://www.readbyqxmd.com/read/28331292/an-open-label-two-period-comparative-study-on-pharmacokinetics-and-safety-of-a-combined-ethinylestradiol-gestodene-transdermal-contraceptive-patch
#10
Chao Zhang, Haiyan Li, Xin Xiong, Suodi Zhai, Yudong Wei, Shuang Zhang, Yuanyuan Zhang, Lin Xu, Li Liu
We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE)/gestodene (GSD) transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet(®)) were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28330384/federal-procurement-of-unlicensed-medicines-in-brazil-findings-and-implications
#11
Cristiane Roberta Dos Santos Teodoro, André Luís Almeida Dos Reis, Brian Godman, Rosângela Caetano, Claudia Garcia Serpa Osorio-de-Castro
BACKGROUND: There are safety concerns with using unlicensed medicines across countries including Brazil. Consequently this needs to be evaluated and concerns address if pertinent. AIM: Investigate such purchases by the Brazilian Federal Government from 2004 to 2013. METHODS: Procurement data from a public-access databank that contains procurement information of the Brazilian Federal Government. Each procured item was cross-referenced to its active drug approval status in the Brazilian National Register (DOU)...
March 23, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28330377/enhanced-oral-bioavailability-and-sustained-delivery-of-glimepiride-via-niosomal-encapsulation-in-vitro-characterization-and-in-vivo-evaluation
#12
Amira Mohamed Mohsen, Mona Mahmoud AbouSamra, Shaimaa Ahmed ElShebiney
This study was designed to investigate the potency of niosomes, for glimepiride (GLM) encapsulation, aiming at enhancing its oral bioavailability and hypoglycemic efficacy. Niosomes containing non-ionic surfactants (NIS) were prepared by thin film hydration technique and characterized. In-vitro release study was performed using a dialysis technique. In-vivo pharmacodynamic studies, as well as pharmacokinetic evaluation were performed on alloxan induced diabetic rats. GLM niosomes exhibited high entrapment efficiency percentages (E...
March 23, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28329820/hepatocellular-toxicity-of-imidazole-and-triazole-antimycotic-agents
#13
Patrizia Haegler, Lorenz Joerin, Stephan Krähenbühl, Jamal Bouitbir
Hepatotoxicity has been described for all antimycotic azoles currently marketed. A possible mechanism involving mitochondrial dysfunction has been postulated for ketoconazole, but not for the other azoles. The aim of the current investigations was to study the toxicity of different azoles in human cell models and to find out mechanisms of their toxicity. In HepG2 cells, posaconazole and ketoconazole were cytotoxic starting at 20 and 50 µM and decreased the cellular ATP content starting at 5 and 10 µM, respectively...
January 27, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28329741/drugs-violence-and-trauma-in-m%C3%A3-xico-and-united-states
#14
Juan Carlos Puyana, Juan Carlos Jacob Puyana, Andres Mariano Rubiano, Jorge Hernan Montenegro, Glyn O Estebanez, Alvaro Ignacio Sanchez, Felipe Vega-Rivera
The impact of illicit drug markets on the occurrence of violence varies tremendously depending on many factors. Over the last years, Mexico and United States (US) has increased security border issues that included many aspects of drug-related trade and criminal activities. Mexico experienced only a small reduction of trauma deaths after severe crime reinforcement policies. This strategy in the war on drugs is shifting the drug market to other Central American countries. This phenomenon is called the ballooning effect where by pressure to control illicit drug related activities in one particular area forces a shift to other more vulnerable areas that lead to increase crime and violence...
March 21, 2017: Medical Principles and Practice: International Journal of the Kuwait University, Health Science Centre
https://www.readbyqxmd.com/read/28329723/analysis-of-synthetic-phenethylamine-street-drugs-using-direct-sample-analysis-coupled-to-accurate-mass-time-of-flight-mass-spectrometry
#15
Maura K McGonigal, Joshua A Wilhide, Philip B Smith, Noelle M Elliott, Frank L Dorman
Serious health complications and fatal overdoses have brought phenethylamine, otherwise known as 2C, drug abuse to the public's attention. These compounds are 2C-X series analogs of mescaline. The name "2C" results from the two carbons in the ethyl chain. The substituents on these emerging drugs are constantly changed in order to avoid listing as controlled substances. These synthetic drugs are marketed as having affects similar to LSD and MDMA and are typically consumed sublingually via blotter paper. Twenty-six commercially available standards were analyzed using a direct sample analysis technique coupled to accurate mass time of flight mass spectrometry...
March 8, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28328020/detection-of-glutathione-conjugates-of-amiodarone-and-its-reactive-diquinone-metabolites-in-rat-bile-using-mass-spectrometry-tools
#16
Keyur R Parmar, Shalu Jhajra, Saranjit Singh
RATIONALE: Amiodarone is reported to cause hepato and pulmonary toxicity in humans, which has been envisaged to be due to formation of its reactive metabolites, essentially based on its structural similarity to benzbromarone, a drug withdrawn from the market due to reasons of similar hepatotoxicity. Therefore, the purpose of this study was to detect glutathione conjugates of amiodarone and its reactive diquinone metabolites in rat bile using mass spectrometry tools. METHODS: Wistar rats were dosed orally with an amiodarone suspension and bile was collected via bile duct cannulation followed by solid-phase extraction, protein precipitation and centrifugation...
May 30, 2016: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28326943/analgesia-induced-by-the-epigenetic-drug-l-acetylcarnitine-outlasts-the-end-of-treatment-in-mouse-models-of-chronic-inflammatory-and-neuropathic-pain
#17
Serena Notartomaso, Giada Mascio, Matteo Bernabucci, Cristina Zappulla, Pamela Scarselli, Milena Cannella, Tiziana Imbriglio, Roberto Gradini, Giuseppe Battaglia, Valeria Bruno, Ferdinando Nicoletti
Background L-acetylcarnitine, a drug marketed for the treatment of chronic pain, causes analgesia by epigenetically up-regulating type-2 metabotropic glutamate (mGlu2) receptors in the spinal cord. Because the epigenetic mechanisms are typically long-lasting, we hypothesized that analgesia could outlast the duration of L-acetylcarnitine treatment in models of inflammatory and neuropathic pain. Results A seven-day treatment with L-acetylcarnitine (100 mg/kg, once a day, i.p.) produced an antiallodynic effect in the complete Freund adjuvant mouse model of chronic inflammatory pain...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28325603/a-path-based-approach-to-assessing-molecular-complexity
#18
John R Proudfoot
An atom environment, path based approach to calculating molecular complexity is described. Based on Shannon's equation, the method transforms the number and diversity of paths emanating from an atom to an atom-complexity from which a number of molecular complexity measures are derived. The method is independent of explicitly predefined features such as ring membership, bond types, chirality or symmetry. These path-based measures of complexity can distinguish subtle differences in molecular structure and an application to the visualization of marketed drugs, including a number of biologics, is presented...
March 9, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28325600/synthesis-and-anti-cancer-activities-of-new-sulfonamides-4-substituted-triazolyl-nucleosides
#19
Soukaina Alaoui, Maeva Dufies, Mohsine Driowya, Luc Demange, Khalid Bougrin, Guillaume Robert, Patrick Auberger, Gilles Pagès, Rachid Benhida
Nucleoside analogues are among the most known drugs commonly used in antiviral and anticancer chemotherapies. Among them, those featuring a five-membered ring nucleobase are of utmost interest such as the anti-cancer agent AICAR or the anti-viral drug ribavirin. Despite its low activity in vitro in different cell lines, AICAR is under clinical development for several pathologies, thanks to its original mode of action. Indeed, AICAR induced autophagy cell death and is able, following this mechanism, to circumvent resistance to apoptotic drugs including kinase inhibitors currently on the market...
March 9, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28325450/classification-of-nervous-system-withdrawn-and-approved-drugs-with-toxprint-features-via-machine-learning-strategies
#20
Aytun Onay, Melih Onay, Osman Abul
BACKGROUND AND OBJECTIVES: Early-phase virtual screening of candidate drug molecules plays a key role in pharmaceutical industry from data mining and machine learning to prevent adverse effects of the drugs. Computational classification methods can distinguish approved drugs from withdrawn ones. We focused on 6 data sets including maximum 110 approved and 110 withdrawn drugs for all and nervous system diseases to distinguish approved drugs from withdrawn ones. METHODS: In this study, we used support vector machines (SVMs) and ensemble methods (EMs) such as boosted and bagged trees to classify drugs into approved and withdrawn categories...
April 2017: Computer Methods and Programs in Biomedicine
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