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https://www.readbyqxmd.com/read/28445961/azilsartan-ameliorates-apoptosis-of-dopaminergic%C3%A2-neurons-and-rescues-characteristic-parkinsonian-behaviors-in-a-rat-model-of-parkinson-s-disease
#1
Qing Gao, Zhou Ou, Teng Jiang, You-Yong Tian, Jun-Shan Zhou, Liang Wu, Jian-Quan Shi, Ying-Dong Zhang
Loss of dopaminergic neurons within the substantia nigra (SN) is a pathological hallmark of Parkinson's disease (PD), which leads to the onset of motor symptoms. Previously, our in vitro studies revealed that Angiotensin II (Ang II) induced apoptosis of dopaminergic neurons through its type 1 receptor (AT1R), but these findings needed to be confirmed via animal experiments. Here, using a rotenone-induced rat model of PD, we observed an overactivation of Ang II/AT1R axis in the SN, since Ang II level and AT1R expression were markedly increased...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445848/a-systematic-and-critical-review-on-bioanalytical-method-validation-using-the-example-of-simultaneous-quantitation-of-antidiabetic-agents-in-blood
#2
REVIEW
Mariana Millan Fachi, Letícia Paula Leonart, Letícia Bonancio Cerqueira, Flavia Lada Degaut Pontes, Michel Leandro de Campos, Roberto Pontarolo
A systematic and critical review was conducted on bioanalytical methods validated to quantify combinations of antidiabetic agents in human blood. The aim of this article was to verify how the validation process of bioanalytical methods is performed and the quality of the published records. The validation assays were evaluated according to international guidelines. The main problems in the validation process are pointed out and discussed to help researchers to choose methods that are truly reliable and can be successfully applied for their intended use...
April 13, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28445012/drug-resistance-patterns-of-multidrug-and-extensively-drug-resistant-tuberculosis-in-korea-amplification-of-resistance-to-oral-second-line-drugs
#3
Chang Ki Kim, So Youn Shin, Hee Jin Kim, Kyungwon Lee
We aimed to analyze the drug resistance patterns of multidrug-resistant and extensively drug-resistant tuberculosis (TB) and the difference of drug resistance among various settings for health care in Korea. The data of drug susceptibility testing in 2009 was analyzed in order to secure sufficient number of patients from various settings in Korea. Patients were categorized by types of institutions into four groups, which comprised new and previously treated patients from public health care centers (PHC), the private sector, and Double-barred Cross clinics (DBC)...
July 2017: Annals of Laboratory Medicine
https://www.readbyqxmd.com/read/28444958/role-of-cytochrome-p450-3a4-and-1a2-phenotyping-in-patients-with-advanced-non-small-cell-lung-cancer-nsclc-receiving-erlotinib-treatment
#4
Zinnia P Parra-Guillen, Peter B Berger, Manuel Haschke, Massimiliano Donzelli, Daria Winogradova, Bogumila Pfister, Martin Früh, Charlotte Kloft, Stephan Krähenbühl, Silke Gillessen, Markus Joerger
Erlotinib is metabolized by cytochrome p450 (CYP) 3A and CYP1A. This study assessed CYP3A4 (midazolam) and CYP1A2 (caffeine) phenotyping in plasma and dried blood spots (DBS) for predicting the pharmacokinetics and toxicity of erlotinib in 36 patients with advanced NSCLC. On day 1, erlotinib 150 mg OD. was initiated, and the 2 oral probe drugs midazolam (2mg) and caffeine (100mg) were added on day 1. Plasma and DBS were collected for erlotinib, OSI-420 and probe drugs for up to 6 hr on day 1 and 2-weekly up to week 10...
April 26, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28444623/treatment-adherence-in-chronic-myeloid-leukaemia-patients-receiving-tyrosine-kinase-inhibitors
#5
Anna Rychter, Piotr Jerzmanowski, Adam Hołub, Zofia Specht-Szwoch, Violetta Kalinowska, Urszula Tęgowska, Ilona Seferyńska, Agnieszka Kołkowska-Leśniak, Ewa Lech-Marańda, Joanna Góra-Tybor
Failure to comply with treatment recommendations is very common in patients, but still poorly recognised by doctors. The current practice of using oral therapy on a large scale has been increasingly adopted for cancer patients. Chronic myeloid leukaemia (CML) is just such an example, where the introduction of taking new oral medications, the tyrosine kinase BCR-ABL inhibitors (TKI), has now revolutionised the treatment. The aim of our study was to assess treatment adherence in a group of Polish CML patients (a survey was conducted on 140 patient aged ≥18 years) treated with oral TKI (imatinib, dasatinib and nilotinib) taking into account the following variables: gender, age, education, place of residence, family circumstances and duration of therapy...
June 2017: Medical Oncology
https://www.readbyqxmd.com/read/28444114/efficacy-of-everolimus-plus-octreotide-lar-in-patients-with-advanced-neuroendocrine-tumor-and-carcinoid-syndrome-final-overall-survival-from-the-randomized-placebo-controlled-phase-3-radiant-2-study
#6
M E Pavel, E Baudin, K E Öberg, J D Hainsworth, M Voi, N Rouyrre, M Peeters, D J Gross, J C Yao
Background: In the phase 3 RADIANT-2 study, everolimus plus octreotide long-acting repeatable (LAR) showed improvement of 5.1 months in median progression-free survival vs placebo plus octreotide LAR among patients with advanced neuroendocrine tumors associated with carcinoid syndrome. The progression-free survival P-value was marginally above the prespecified threshold for statistical significance. Here, we report final overall survival (OS) and key safety update from RADIANT-2. Patients and methods: The RADIANT-2 trial compared everolimus (10 mg/day, orally; n= 216) vs placebo ( n= 213), both in conjunction with octreotide LAR (30 mg, intramuscularly, every 28 days)...
April 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28443914/probing-the-pharmacokinetics-of-cucurbit-7-8-and-10-uril-and-a-dinuclear-ruthenium-antimicrobial-complex-encapsulated-in-cucurbit-10-uril
#7
Fangfei Li, Anil K Gorle, Marie Ranson, Kara L Vine, Robert Kinobe, Marshall Feterl, Jeffrey M Warner, F Richard Keene, J Grant Collins, Anthony I Day
The relatively non-toxic family of cucurbit[n]uril, Q[n], have shown considerable potential in vitro as drug delivery agents, with only a few examples of pharmacokinetic (PK) studies for drug⊂Q[n]. Drug-free Q[n] PK studies are the next step in determining the pharmacological applicability in their drug delivery potential. The results for the first PK and bio-distribution of drug-free (14)C-Q[7] are described for administration via intravenous (i.v.) and intraperitoneal (i.p.) dosing. A study of oral administration of drug-free (14)C-Q[8] has also been undertaken to determine the time course for the gastrointestinal tract (GIT), absorption and subsequent bio-distribution...
April 26, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28443252/open-label-phase-ii-clinical-trial-in-75-patients-with-advanced-hepatocellular-carcinoma-receiving-daily-dose-of-tableted-liver-cancer-vaccine-hepcortespenlisimut-l
#8
Marina G Tarakanovskaya, Jigjidsuren Chinburen, Purev Batchuluun, Chogsom Munkhzaya, Genden Purevsuren, Dorjiin Dandii, Tsogkhuu Hulan, Dandii Oyungerel, Galyna A Kutsyna, Alan A Reid, Vika Borisova, Allen I Bain, Vichai Jirathitikal, Aldar S Bourinbaiar
BACKGROUND: An increasing number of studies is now devoted to immunotherapy of cancer. We evaluated the clinical benefit of hepcortespenlisimut-L (Hepko-V5 [formerly known as V5])-an oral therapeutic vaccine designated by the United States Food and Drug Administration (FDA) as an orphan drug for treatment of hepatocellular carcinoma (HCC). V5 was initially developed by us in 2002 to treat hepatitis B or C viral infections and liver cirrhosis. METHODS: The outcome of open-label Phase II trial of daily dose of V5 pill was analyzed retrospectively...
2017: Journal of Hepatocellular Carcinoma
https://www.readbyqxmd.com/read/28442935/new-developments-in-the-treatment-of-hypoactive-sexual-desire-disorder-a-focus-on-flibanserin
#9
REVIEW
Christopher J Jayne, Michael J Heard, Sarah Zubair, Dustie L Johnson
The objective of the authors is to highlight the historical complexities for the diagnosis and treatment of hypoactive sexual desire disorder (HSDD) with a focus on Flibanserin. A systematic review of the medical literature published in PubMed using the search terms HSDD and Flibanserin was conducted. Each author reviewed the results of the systematic review for articles to include in this study. HSDD is defined as a persistent or recurrent deficiency or absence of sexual fantasies and desire for sexual activity causing marked distress or interpersonal difficulty that is not better accounted for by another diagnosis...
2017: International Journal of Women's Health
https://www.readbyqxmd.com/read/28442928/the-efficacy-and-safety-of-s-flurbiprofen-plaster-in-the-treatment-of-knee-osteoarthritis-a-phase-ii-randomized-double-blind-placebo-controlled-dose-finding-study
#10
Ikuko Yataba, Noboru Otsuka, Isao Matsushita, Hideo Matsumoto, Yuichi Hoshino
BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) patches are convenient for use and show much less gastrointestinal side effects than oral NSAIDs, whereas its percutaneous absorption is not sufficient for the expression of clinical efficacy at satisfactory level. S-flurbiprofen plaster (SFPP) has shown dramatic improvement in percutaneous absorption results from animal and clinical studies. In this study, the efficacy and safety of SFPP were compared with placebo in patients with knee osteoarthritis (OA) to determine its optimal dose...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28442915/efficacy-and-safety-outcomes-of-sofosbuvir-based-treatment-regimens-for-hepatitis-c-virus-infected-patients-with-or-without-cirrhosis-from-phase-iii-clinical-trials
#11
REVIEW
Young-Mo Yang, Eun Joo Choi
BACKGROUND: With the appearance of oral direct-acting antivirals (DAAs), the field of hepatitis C virus (HCV) treatment has been dramatically changed. This evolution makes possible for all oral treatments to be available for the treatment of HCV-infected patients. The aims of this review were to report the efficacy and safety of sofosbuvir (SOF)-based regimens for the treatment of patients with chronic HCV infection and to provide our clinical perspectives on these regimens. METHODS: A literature search of clinical studies published in PubMed and posted on ClinicalTrials...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28442580/ethanol-reversal-of-tolerance-to-the-antinociceptive-effects-of-oxycodone-and-hydrocodone
#12
Joanna C Jacob, Justin L Poklis, Hamid I Akbarali, Graeme Henderson, William L Dewey
This study compared the development of tolerance and its reversal by ethanol of two orally-bioavailable prescription opioids, oxycodone and hydrocodone, to that of morphine. Oxycodone (s.c) was significantly more potent in the mouse tail withdrawal assay than either morphine or hydrocodone. Oxycodone was also significantly more potent in this assay than hydrocodone when administered orally. Tolerance was seen following chronic subcutaneous administration of each of the three drugs and by the chronic administration of oral oxycodone, but not following the chronic oral administration of hydrocodone...
April 25, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28442499/absorption-distribution-metabolism-and-excretion-of-the-oral-prostaglandin-d2-receptor-2-dp2-antagonist-fevipiprant-qaw039-in-healthy-volunteers-and-in-vitro
#13
David Pearson, H Markus Weiss, Yi Jin, Jan Jaap van Lier, Veit J Erpenbeck, Ulrike Glaenzel, Peter End, Ralph Woessner, Fabian Eggimann, Gian Camenisch
Fevipiprant is a novel oral prostaglandin D2 receptor 2 (DP2; also known as CRTh2) antagonist, which is currently in development for the treatment of severe asthma and atopic dermatitis. We investigated the absorption, distribution, metabolism, and excretion properties of fevipiprant in healthy subjects after a single 200 mg oral dose of [(14)C]-radiolabeled fevipiprant. Fevipiprant and metabolites were analyzed by liquid chromatography coupled to tandem mass spectrometry and radioactivity measurements, and mechanistic in vitro studies were performed to investigate clearance pathways and covalent plasma protein binding...
April 25, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28442411/evaluation-of-the-bioactive-extract-of-actinomyces-isolated-from-the-egyptian-environment-against-aflatoxin-b1-induce-cytotoxicity-genotoxicity-and-oxidative-stress-in-the-liver-of-rats
#14
Aziza A El-Nekeety, Asmaa S Salman, Amal S Hathout, Bassem A Sabry, Sekena H Abdel-Aziem, Nabila S Hassan, Mosaad A Abdel-Wahhab
This study aimed to determine the bioactive compounds of actinomyces (ACT) isolated from the Egyptian environment (D-EGY) and to evaluate their protective activity against AFB1 in female Sprague-Dawley rats. Six groups of animals were treated orally for 3 weeks included: C, the control group, T1, AFB1-treated group (80 μg/kg b.w), T2 and T3, the groups received ACT extract at low (25 mg/kg b.w) or high (50 mg/kg b.w) doses, T4 and T5, the groups received AFB1 plus the low or high dose of ACT extract. Blood, bone marrow and tissue samples were collected for different analyses and histological examination...
April 22, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28442322/in-vitro-and-in-vivo-antitumor-activities-of-t-3764518-a-novel-and-orally-available-small-molecule-stearoyl-coa-desaturase-1-inhibitor
#15
Satoru Nishizawa, Hiroyuki Sumi, Yoshihiko Satoh, Yukiko Yamamoto, Satoshi Kitazawa, Kohei Honda, Hideo Araki, Kazuyo Kakoi, Keisuke Imamura, Masako Sasaki, Ikuo Miyahisa, Yoshinori Satomi, Ryuuichi Nishigaki, Megumi Hirayama, Kazunobu Aoyama, Hironobu Maezaki, Takahito Hara
Most cancer cells are characterized by elevated lipid biosynthesis. The rapid proliferation of cancer cells requires de novo synthesis of fatty acids. Stearoyl-CoA desaturase-1 (SCD1), a key enzyme for lipogenesis, is overexpressed in various types of cancer and plays an important role in cancer cell proliferation. Therefore, it has been studied as a candidate target for cancer therapy. In this study, we demonstrate the pharmacological properties of T-3764518, a novel and orally available small molecule inhibitor of SCD1...
April 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28442108/effect-of-egyptian-propolis-on-cryptosporidiosis-in-immunosuppressed-rats-with-special-emphasis-on-oocysts-shedding-leukogram-protein-profile-and-ileum-histopathology
#16
Hamdy Soufy, Nadia M El-Beih, Soad M Nasr, Tamer H Abd El-Aziz, Fathia A M Khalil, Youssef F Ahmed, Hala A A Abou Zeina
OBJECTIVES: To investigate the activity of Egyptian propolis extracts (ethanol and water) on cryptosporidiosis in experimentally infected dexamethasone-immunosuppressed rats. METHODS: A total of 180 male rats (190-220) g BWt were randomly divided into 9 equal groups (G1-G9). Groups of rats were kept as (G1): normal control, (G2-G9): immunosuppressed with dexamethasone and (G3-G9): infected with Cryptosporidium oocysts. Rats from (G4-G9) were given orally ethanol and water extract of propolis (at a dose of 50 mg/kg BWt) and nitazoxanide (standard anti-cryptosporidial drug at a dose of 100 mg/kg BWt) to infected rats with different regimes...
March 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28441966/maintenance-tegafur-uracil-versus-observation-following-an-adjuvant-oxaliplatin-based-regimen-in-patients-with-stage-iii-colon-cancer-after-radical-resection-study-protocol-for-a-randomized-controlled-trial
#17
Yung-Sung Yeh, Hsiang-Lin Tsai, Ching-Wen Huang, Po-Li Wei, Yung-Chuan Sung, Hsiu-Chih Tang, Jaw-Yuan Wang
BACKGROUND: We conducted a prospective randomized study of an adjuvant oxaliplatin-based regimen plus orally administered tegafur-uracil in patients with stage III colon cancer after radical resection to evaluate the feasibility of this drug combination in cancer clinical outcomes, acute toxicity, disease-free survival (DFS), and overall survival (OS) in Taiwan. METHODS/DESIGN: This is an open-label, randomized, comparative, double-arm, multicenter, phase III study to assess DFS, OS, and safety profiles of the aforementioned drug combination as maintenance therapy for 1 year in patients with stage III colon cancer after radical resection in Taiwan...
April 26, 2017: Trials
https://www.readbyqxmd.com/read/28441890/rosuvastatin-ameliorates-cognitive-impairment-in-rats-fed-with-high-salt-and-cholesterol-diet-via-inhibiting-acetylcholinesterase-activity-and-amyloid-beta-peptide-aggregation
#18
I Husain, M Akhtar, M Zainul Abdin, M Islamuddin, M Shaharyar, A K Najmi
Amyloid beta (Aβ) peptide aggregation and cholinergic neurodegeneration are involved in the development of cognitive impairment. Therefore, in this article, we examined rosuvastatin (RSV), an oral hypolipidemic drug, to determine its potential as a dual inhibitor of acetylcholinesterase (AChE) and Aβ peptide aggregation for the treatment of cognitive impairment. Molecular docking study was done to examine the affinity of RSV with Aβ1-42 and AChE in silico. We also employed neurobehavioral activity tests, biochemical estimation, and histopathology to study the anti-Aβ1-42 aggregation capability of RSV in vivo...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28441497/development-of-a-biorelevant-material-sparing-membrane-flux-test-for-rapid-screening-of-bioavailability-enhancing-drug-product-formulations
#19
Aaron M Stewart, Michael E Grass, Deanna M Mudie, Michael M Morgen, Dwayne T Friesen, David T Vodak
Bioavailability-enhancing formulations are often used to overcome challenges of poor gastrointestinal solubility for drug substances developed for oral administration. Conventional in vitro dissolution tests often do not properly compare such formulations due to the many different drug species that may exist in solution. To overcome these limitations, we have designed a practical in vitro membrane flux test, requiring minimal active pharmaceutical ingredient (API) and capable of rapidly screening many drug product intermediates...
April 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28441383/the-oral-vegf-receptor-tyrosine-kinase-inhibitor-pazopanib-in-combination-with-the-mek-inhibitor-trametinib-in-advanced-cholangiocarcinoma
#20
Rachna T Shroff, Mark Yarchoan, Ashley O'Connor, Denise Gallagher, Marianna L Zahurak, Gary Rosner, Chimela Ohaji, Susan Sartorius-Mergenthaler, Vivek Subbiah, Ralph Zinner, Nilofer S Azad
BACKGROUND: Cholangiocarcinoma is an aggressive malignancy with limited therapeutic options. MEK inhibition and antiangiogenic therapies have individually shown modest activity in advanced cholangiocarcinoma, whereas dual inhibition of these pathways has not been previously evaluated. We evaluated the safety and efficacy of combination therapy with the oral VEGF receptor tyrosine kinase inhibitor pazopanib plus the MEK inhibitor trametinib in patients with advanced cholangiocarcinoma...
April 25, 2017: British Journal of Cancer
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