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https://www.readbyqxmd.com/read/28932928/a-phase-i-study-to-assess-the-mass-balance-excretion-and-pharmacokinetics-of-14-c-ixazomib-an-oral-proteasome-inhibitor-in-patients-with-advanced-solid-tumors
#1
Neeraj Gupta, Steven Zhang, Sandeepraj Pusalkar, Mihaela Plesescu, Swapan Chowdhury, Michael J Hanley, Bingxia Wang, Cindy Xia, Xiaoquan Zhang, Karthik Venkatakrishnan, Dale R Shepard
This two-part, phase I study evaluated the mass balance, excretion, pharmacokinetics (PK), and safety of ixazomib in patients with advanced solid tumors. In Part A of the study, patients received a single 4.1 mg oral solution dose of [(14)C]-ixazomib containing ~500 nCi total radioactivity (TRA), followed by non-radiolabeled ixazomib (4 mg capsule) on days 14 and 21 of the 35-day PK cycle. Patients were confined to the clinic for the first 168 h post dose and returned for 24 h overnight clinic visits on days 14, 21, 28, and 35...
September 21, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28930286/molecular-and-cellular-signatures-underlying-superior-immunity-against-bordetella-pertussis-upon-pulmonary-vaccination
#2
R Hm Raeven, J Brummelman, J LA Pennings, L van der Maas, K Helm, W Tilstra, A van der Ark, A Sloots, P van der Ley, W van Eden, W Jiskoot, E van Riet, C Acm van Els, G Fa Kersten, W Gh Han, B Metz
Mucosal immunity is often required for protection against respiratory pathogens but the underlying cellular and molecular mechanisms of induction remain poorly understood. Here, systems vaccinology was used to identify immune signatures after pulmonary or subcutaneous immunization of mice with pertussis outer membrane vesicles. Pulmonary immunization led to improved protection, exclusively induced mucosal immunoglobulin A (IgA) and T helper type 17 (Th17) responses, and in addition evoked elevated systemic immunoglobulin G (IgG) antibody levels, IgG-producing plasma cells, memory B cells, and Th17 cells...
September 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28930253/in-vitro-and-in-vivo-evaluation-of-essential-oil-from-artemisia-absinthium-l-formulated-in-nanocochleates-against-cutaneous-leishmaniasis
#3
Beatriz Tamargo, Lianet Monzote, Abel Piñón, Laura Machín, Marley García, Ramón Scull, William N Setzer
Background: Leishmaniasis is a zoonotic disease caused by protozoan parasites from Leishmania genus. Currently, there are no effective vaccines available and the available therapies are far from ideal. In particular, the development of new therapeutic strategies to reduce the infection caused by Leishmania amazonensis could be considered desirable. Different plant-derived products have demonstrated antileishmanial activity, including the essential oil (EO) from Artemisia absinthium L. (EO-Aa), Asteraceae. Methods: In the present study, the EO-Aa formulated in nanocochleates (EO-Aa-NC) was investigated in vitro against intracellular amastigotes of L...
June 9, 2017: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/28929046/application-of-three-dimensional-printing-for-colon-targeted-drug-delivery-systems
#4
REVIEW
Nitin B Charbe, Paul A McCarron, Majella E Lane, Murtaza M Tambuwala
Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption...
April 2017: International Journal of Pharmaceutical Investigation
https://www.readbyqxmd.com/read/28928662/toxicity-of-nanoparticles-on-the-reproductive-system-in-animal-models-a-review
#5
REVIEW
Rahim Dad Brohi, Li Wang, Hira Sajjad Talpur, Di Wu, Farhan Anwar Khan, Dinesh Bhattarai, Zia-Ur Rehman, F Farmanullah, Li-Jun Huo
In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28927311/successes-and-failures-in-human-tuberculosis-vaccine-development
#6
Roberto Zenteno-Cuevas
Tuberculosis (TB) is an infectious disease caused mainly by Mycobacterium tuberculosis. In 2016, the WHO estimated 10.5 million new cases and 1.8 million deaths, making this disease the leading cause of death by an infectious agent. The current and projected TB situation necessitates the development of new vaccines with improved attributes compared to the traditional BCG method. Areas covered: In this review, the authors describe the most promising candidate vaccines against TB and discuss additional key elements in vaccine development, such as animal models, new adjuvants and immunization routes and new strategies for the identification of candidate vaccines...
September 19, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28926943/monoclonal-antibodies-in-preclinical-eae-models-of-multiple-sclerosis-a-systematic-review
#7
REVIEW
Katja Schmitz, Gerd Geisslinger, Irmgard Tegeder
Monoclonal antibodies (mAb) are promising therapeutics in multiple sclerosis and multiple new candidates have been developed, hence increasing the need for some agreement for preclinical mAb studies. We systematically analyzed publications of experimental autoimmune encephalomyelitis (EAE) studies showing effects of monoclonal antibodies. A PubMed search retrieved 570 records, out of which 122 studies with 253 experiments were eligible based on experimental design, number of animals and presentation of time courses of EAE scores...
September 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28923683/a-hydrogel-matrix-prolongs-persistence-and-promotes-specific-localization-of-an-oncolytic-adenovirus-in-a-tumor-by-restricting-nonspecific-shedding-and-an-antiviral-immune-response
#8
Bo-Kyeong Jung, Eonju Oh, JinWoo Hong, Yunki Lee, Ki Dong Park, Chae-Ok Yun
Currently, intratumoral injection of an oncolytic adenovirus (Ad) is the conventional administration route in clinical trials. Nonetheless, the locally administered Ad disseminates to the surrounding nontarget tissues and has short biological activity due to immunogenicity of Ad, thus necessitating multiple injections to achieve a sufficient therapeutic index. In the present study, a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-expressing oncolytic Ad (oAd-TRAIL) was encapsulated in a gelatin hydrogel (oAd-TRAIL/gel) to enhance and prolong antitumor efficacy of the virus after a single intratumoral injection...
September 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/28922956/dmts-is-an-effective-treatment-in-both-inhalation-and-injection-models-for-cyanide-poisoning-using-unanesthetized-mice
#9
Susan M DeLeon, Jason D Downey, Diane M Hildenberger, Melissa O Rhoomes, Lamont Booker, Gary A Rockwood, Kelly A Basi
CONTEXT: Cyanide (CN) is a metabolic poison, halting ATP synthesis by inhibiting complex IV of the electron transport chain. If exposed at high enough concentrations, humans and most animals can die within minutes. Because time is a crucial factor in survival of CN poisoning, a rapidly bioavailable, nontoxic, easy to administer CN medical countermeasure could improve morbidity/mortality in a mass CN exposure scenario. The most likely route of exposure to CN is via inhalation. OBJECTIVE: This study examined the efficacy of a new formulation for dimethyl trisulfide (DMTS), a countermeasure which has shown promise as a treatment for CN poisoning, using both inhalation and injection models of CN exposure...
September 19, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28921648/rna-therapeutics-in-oncology-advances-challenges-and-future-directions
#10
A Robert MacLeod, Stanley T Crooke
RNA-based therapeutic technologies represent a rapidly expanding class of therapeutic opportunities with the power to modulate cellular biology in ways never before possible. With RNA-targeted therapeutics, inhibitors of previously undruggable proteins, gene expression modulators, and even therapeutic proteins can be rationally designed based on sequence information alone, something that is not possible with other therapeutic modalities. The most advanced RNA therapeutic modalities are antisense oligonucleotides (ASOs) and small interfering RNAs...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921444/polyester-based-nanoparticles-for-delivery-of-therapeutic-proteins
#11
Pedro Fonte, Flávia Sousa, Bruno Sarmento
Therapeutic proteins are widely used to treat severe conditions, such as oncologic and metabolic diseases, and also for vaccination. They are recognized for its high biopotency, but their hydrophilicity and high molecular weight make its transport through membranes difficult to achieve. They may also suffer in vivo structural instability caused by a proteolytic cleavage, turning them biological inactive. Polyester-based nanoparticles are useful tools to overcome such problems, and deliver therapeutic proteins in a controlled and localized manner, decreasing the number of administrations needed and enhancing the therapeutic outcome...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28920790/pharmacokinetics-efficacy-and-safety-of-voriconazole-and-itraconazole-in-healthy-cottonmouths-agkistrodon-piscivorus-and-massasauga-rattlesnakes-sistrurus-catenatus-with-snake-fungal-disease
#12
Dana M Lindemann, Matthew C Allender, Marta Rzadkowska, Grace Archer, Lauren Kane, Eric Baitchman, Elizabeth A Driskell, Caroline T Chu, Kuldeep Singh, Shih-Hsuan Hsiao, John M Sykes, Sherry Cox
Snake fungal disease (SFD; Ophidiomyces ophiodiicola) is posing a significant threat to several free-ranging populations of pitvipers. Triazole antifungals have been proposed for the treatment of mycoses in reptiles; however, data are lacking about their safety and efficacy in snakes with SFD. Study 1 investigated in vitro susceptibility, and identified that plasma concentrations >250 ng/ml (voriconazole) and >1,000 ng/ml (itraconazole) may be effective in vivo for SFD. In Study 2, the pharmacokinetics after a single subcutaneous voriconazole injection were assessed in apparently healthy free-ranging cottonmouths (Agkistrodon piscivorus)...
September 2017: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
https://www.readbyqxmd.com/read/28920748/investigation-of-the-transport-and-absorption-of-angelica-sinensis-polysaccharide-through-gastrointestinal-tract-both-in-vitro-and-in-vivo
#13
Kaiping Wang, Fang Cheng, Xianglin Pan, Tao Zhou, Xiqiu Liu, Ziming Zheng, Li Luo, Yu Zhang
To investigate the absorption and delivery of ASP in gastrointestinal (GI) tract, cASP was successfully synthesized by chemically modifying with succinic anhydride and then conjugating with a near infrared fluorescent dye Cy5.5. Then, the capacity of oral absorption of cASP was evaluated. The results demonstrated that cASP had low toxicity and no disruption on the integrity of cell membrane. The endocytosis of cASP into the epithelial cells was time- and energy-dependent, which was mediated by macropinocytosis pathway and clathrin- and caveolae (or lipid raft)-related routes...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28918025/effect-of-calcium-carbonate-encapsulation-on-the-activity-of-orally-administered-cpg-oligonucleotides
#14
Neslihan Kayraklioglu, Julia Scheiermann, W Gregory Alvord, Dennis M Klinman
Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODNs) stimulate immune cells via Toll-like receptor 9 (TLR9). Because oligodeoxynucleotides (ODNs) are susceptible to gastric degradation, clinical trials designed to evaluate their therapeutic utility have relied solely on parenteral routes of administration. A strategy to improve the activity of orally delivered ODNs by reducing their susceptibility to gastrointestinal (GI) digestion via encapsulation in calcium carbonate nanoparticles (ODNcaps) was recently described...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917988/a-comprehensive-screening-platform-for-aerosolizable-protein-formulations-for-intranasal-and-pulmonary-drug-delivery
#15
Martina Röhm, Stefan Carle, Frank Maigler, Johannes Flamm, Viktoria Kramer, Chrystelle Mavoungou, Otmar Schmid, Katharina Schindowski
Aerosolized administration of biopharmaceuticals to the airways is a promising route for nasal and pulmonary drug delivery, but - in contrast to small molecules - little is known about the effects of aerosolization on safety and efficacy of biopharmaceuticals. Proteins are sensitive against aerosolization-associated shear stress. Tailored formulations can shield proteins and enhance permeation, but formulation development requires extensive screening approaches. Thus, the aim of this study was to develop a cell-based in vitro technology platform that includes screening of protein quality after aerosolization and transepithelial permeation...
September 13, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28917081/evaluation-of-the-ecstasy-influence-on-tramadol-and-its-main-metabolite-plasma-concentration-in-rats
#16
Bardia Jamali, Behjat Sheikholeslami, Yalda Hosseinzadeh Ardakani, Hoda Lavasani, Mohammad-Reza Rouini
BACKGROUND: Tramadol is prone to be abused alone, or in combination with 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy). It was reported that 95% of people with a history of substance abuse in the United States used tramadol in 2004. According to the WHO report in 2016, there was a growing number of tramadol abusers alone or in combination with psychoactive substances such as MDMA in particular in some Middle East countries. Higher concentrations of tramadol in plasma may lead to adverse drug reactions or lethal intoxication...
September 16, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28913643/does-oxytocin-lead-to-emotional-interference-during-a-working-memory-paradigm
#17
Marieke S Tollenaar, M Ruissen, B M Elzinga, E R A de Bruijn
BACKGROUND: Oxytocin administration may increase attention to emotional information. We hypothesized that this augmented emotional processing might in turn lead to interference on concurrent cognitive tasks. To test this hypothesis, we examined whether oxytocin administration would lead to heightened emotional interference during a working memory paradigm. Additionally, moderating effects of childhood maltreatment were explored. METHODS: Seventy-eight healthy males received 24 IU of intranasal oxytocin or placebo in a randomized placebo-controlled double-blind between-subjects study...
September 14, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28912036/dual-effects-of-the-pi3k-inhibitor-zstk474-on-multidrug-efflux-pumps-in-resistant-cancer-cells
#18
Divya Muthiah, Richard Callaghan
ZSTK474 is a potent phosphoinositide 3-kinase (PI3K) inhibitor that reduces cell proliferation via G1-arrest. However, there is little information on the susceptibility of this anticancer drug to resistance conferred by the multidrug pumps P-glycoprotein (ABCB1) and ABCG2. We have demonstrated that ZSTK474 generated cytotoxicity in cells over-expressing either pump with potency similar to that in drug sensitive cells. In addition, the co-administration of ZSTK474 with the cytotoxic anti-cancer drugs vinblastine and mitoxantrone caused a potentiated cytotoxic effect in both drug sensitive and efflux pump expressing cells...
September 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28911882/aromatase-inhibitors-a-new-approach-for-controlling-ovarian-function-in-cattle
#19
M J Yapura, E M Zwiefelhofer, R A Pierson, G P Adams
Numerous treatments and protocols have been used to control the reproductive cycle in cattle, with varying effectiveness and many involving the administration of steroid hormones. Steroid hormones, such as estradiol, are perceived as having a negative impact on consumer health. This internationally shared opinion has led to a ban on the use of steroid hormones in food producing animals in many countries (i.e., European Union, New Zealand, and Australia). Letrozole, a non-steroidal aromatase inhibitor, inactivates the aromatase enzyme responsible for the synthesis of estrogens by reversibly binding to the "heme" group of the P450 subunit...
September 11, 2017: Theriogenology
https://www.readbyqxmd.com/read/28911247/metabolic-pathways-and-pharmacokinetics-of-natural-medicines-with-low-permeability
#20
Mei Zeng, Lan Yang, Dan He, Yao Li, Mingxin Shi, Jingqing Zhang
Drug metabolism plays an important role in the drug disposal process. Differences in pharmacokinetics among individuals are the basis for personalized medicine. Natural medicines, formed by long-term evolution of nature, prioritize the action of a target protein with a drug. Natural medicines are valued for structural diversity, low toxicity, low cost, and definite biological activities. Metabolic pathway and pharmacokinetic research of natural medicines is highly beneficial for clinical dose adjustment and the development of personalized medicine...
September 14, 2017: Drug Metabolism Reviews
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