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https://www.readbyqxmd.com/read/29162627/a-therapeutic-combination-of-gpcr-modulators-that-protects-photoreceptors-from-degeneration
#1
Tivadar Orban, Henri Leinonen, Tamar Getter, Zhiqian Dong, Wenyu Sun, Songqi Gao, Alexander Veenstra, Hossein Heidari-Torkabadi, Timothy S Kern, Philip D Kiser, Krzysztof Palczewski
Degeneration of retinal photoreceptor cells can arise from environmental and/or genetic causes. Since photoreceptor cells, the retinal pigment epithelium (RPE), neurons and glial cells of the retina are intimately associated; all cell types eventually are affected by retinal degenerative diseases. Such diseases often originate either in rod and/or cone photoreceptor cells or the RPE. Of these, cone cells located in the central retina are especially important for daily human activity. Here we describe the protection of cone cells by a combination therapy consisting of the G protein-coupled receptor modulators metoprolol, tamsulosin, and bromocriptine...
November 21, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29160125/effects-of-paeoniflorin-on-the-activities-and-mrna-expression-of-rat-cyp1a2-cyp2c11-and-cyp3a1-enzymes-in-vivo
#2
Sicong Li, Xuting Li, Dingsheng Yuan, Bin Wang, Rui Yang, Min Zhang, Jinliang Li, Fuqiang Zeng
1. Paeoniflorin is the major constituent in extracts of the peony root, the purpose of the present study was to assess the effects of paeoniflorin on the activities and mRNA expression of the rat hepatic drug-metabolizing enzymes cytochrome P450 (CYP1A2), CYP2C11 and CYP3A1 in vivo. 2. Sprague-Dawley (SD) male rats were treated with paeoniflorin at the dosage of 25, 50 and 100 mg/kg or 0.9% sodium chloride solution by intragastric administration for 7 days, then were given probe drugs phenacetin (CYP1A2), tolbutamide (CYP2C11), or midazolam (CYP3A1) orally on the eighth day...
November 21, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29156431/pathway-of-oxfendazole-from-the-host-into-the-worm-trichuris-suis-in-pigs
#3
Tina V A Hansen, Andrew R Williams, Matthew Denwood, Peter Nejsum, Stig M Thamsborg, Christian Friis
It is well known that the efficacy of a single oral dose of benzimidazoles against Trichuris spp. infections in humans and animals is poor, but is currently still used in control programmes against human trichuriasis. However, the route of the benzimidazoles from the treated host to Trichuris remains unknown. As parts of adult Trichuris are situated intracellularly in the caecum, they might be exposed to anthelmintic drugs in the intestinal content as well as the mucosa. In this study, the pathway of oxfendazole and its metabolites was explored using a T...
November 9, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29150845/effect-of-sorbitol-on-the-pharmacokinetic-profile-of-lamivudine-oral-solution-in-adults-an-open-label-randomized-study
#4
Kimberly Adkison, Allen Wolstenholme, Yu Lou, Zhiping Zhang, Amy Eld, Teodora Perger, Harald Vangerow, Katy Hayward, Mark Shaefer, Cynthia McCoig
In children aged ≤4 years, the relative bioavailability of lamivudine oral solution was 37% lower than that of a tablet formulation. An open-label, 4-way crossover study was conducted in healthy adults to evaluate the effect of sorbitol, a common liquid excipient, on the pharmacokinetics of lamivudine oral solution (ClinicalTrials.gov identifier, NCT02634073). Sixteen subjects were randomized to 1 of 4 sequences consisting of 4 doses of lamivudine 300 mg (10 mg/mL) alone or with sorbitol 3.2, 10.2, or 13...
November 18, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29147872/fluidized-bed-hot-melt-granulation-as-a-tool-to-improve-curcuminoid-solubility
#5
Cristiane C C Teixeira, Elias de Paiva Junior, Luis Alexandre Pedro de Freitas
Curcumin is the main bioactive component of Curcuma longa L. and has recently aroused growing interest from the scientific community. Unfortunately, the medicinal properties attributed to curcuminoids are impaired by their low oral bioavailability or low solubility in aqueous solutions. Many strategies have been studied to improve curcumin solubility; however, the preparation of granules using hydrophilic materials has never been attempted. The aim of this work was to develop curcumin granules by fluidized bed hot-melt granulation using the hydrophilic carrier Gelucire® 50:13...
November 16, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/29145890/pharmacokinetic-study-of-single-and-multiple-dosing-with-metolazone-tablets-in-healthy-chinese-population
#6
Xueqing Li, Rutao Wang, Yang Liu, Yun Liu, Heng Zheng, Yabo Feng, Na Zhao, Hongbin Geng, Wanzhi Zhang, Aidong Wen
BACKGROUND: Metolazone is a diuretic, saluretic and antihypertensive chemical compound from the quinazoline category that possesses medicinal features similar to those of other thiazide diuretic drugs. However, the pharmacokinetics of metolazone in the Chinese population has rarely been studied. This study aimed to examine the pharmacokinetic characteristics, safety characteristic, and tolerability of metolazone in healthy Chinese subjects after single and multiple doses taken orally as well as the effects that food and gender have on oral metolazone pharmacokinetic parameters...
November 16, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29144822/testosterone-levels-achieved-by-medically-treated-transgender-women-in-a-united-states-endocrinology-clinic-cohort
#7
Jennifer J Liang, Divya Jolly, Kelly J Chan, Joshua D Safer
OBJECTIVE: Most transgender women depend on medical treatment alone to lower testosterone levels in order to align physical appearance with gender identity. The medical regimen in the United States typically includes spironolactone and estrogens. The purpose of this cross-sectional study was to assess the testosterone suppression achieved among transgender women treated with spironolactone and estrogens. METHODS: Testosterone and estradiol levels were extracted from the electronic medical records of 98 anonymized transgender women treated with oral spironolactone and oral estrogen therapy at the Endocrinology Clinic at Boston Medical Center...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29142437/docking-based-screening-of-ficus-religiosa-phytochemicals-as-inhibitors-of-human-histamine-h2-receptor
#8
Amit Chaudhary, Birendra Singh Yadav, Swati Singh, Pramod Kumar Maurya, Alok Mishra, Shweta Srivastva, Pritish Kumar Varadwaj, Nand Kumar Singh, Ashutosh Mani
Background: Ficus religiosa L. is generally known as Peepal and belongs to family Moraceae. The tree is a source of many compounds having high medicinal value. In gastrointestinal tract, histamine H2 receptors have key role in histamine-stimulated gastric acid secretion. Their over stimulation causes its excessive production which is responsible for gastric ulcer. Objective: This study aims to screen the range of phytochemicals present in F. religiosa for binding with human histamine H2 and identify therapeutics for a gastric ulcer from the plant...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29140478/comparison-of-cocaine-crack-biomarkers-concentrations-in-oral-fluid-urine-and-plasma-simultaneously-collected-from-drug-users
#9
Taís Regina Fiorentin, Juliana Nichterwitz Scherer, Marcelo Caetano Alexandre Marcelo, Tanara Rosângela Vieira Sousa, Flavio Pechansky, Marco Flôres Ferrão, Renata Pereira Limberger
The use of oral fluid (OF) as an alternative specimen for drug analysis has become very popular in forensic toxicology. Many clinical studies have evaluated the correlations between concentrations of cocaine and its metabolites in OF and other matrices, but results have shown high variability. In addition, there are no data available regarding the correlations between biomarkers of crack-cocaine use in different matrices. This study evaluated the relationship between concentrations of cocaine/crack-cocaine biomarkers in OF, urine and plasma samples collected from cocaine users...
November 13, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/29125075/-treatment-of-paracetamol-intoxication-taking-into-consideration-dosage-route-of-administration-and-risk-factors
#10
A Koppen, A J H P van Riel, A Nugteren-van Lonkhuyzen, I de Vries
- Paracetamol is the drug for which the Dutch Poisons Information Centre (DPIC) receives the most information requests.- The protocol for the treatment of single acute oral paracetamol intoxications is clear, however, ambiguity exists concerning the treatment of intoxications with repeated supratherapeutic doses of paracetamol.- Paracetamol intoxications with liquid preparations, extended-release tablets, exposure routes other than oral, and repeated supratherapeutic ingestions require a tailored approach.- An increased risk of liver damage due to paracetamol intoxication has to be taken into account for patients who consume excessive levels of alcohol, are malnourished or have a pre-existing liver condition...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/29120380/in-vitro-phase-i-metabolism-of-crv431-a-novel-oral-drug-candidate-for-chronic-hepatitis-b
#11
Daniel J Trepanier, Daren R Ure, Robert T Foster
The cytochrome P450-mediated Phase I in vitro metabolism of CRV431 was studied using selective chemical inhibition and recombinant human enzymes. Additionally, the metabolic profile of CRV431 in human, rat, and monkey liver microsomes was investigated. Liver microsomes were incubated for 0-80 min with CRV431, and the metabolite profile was assessed by electrospray ionization liquid chromatography mass spectrometry (ESI-LCMS). CRV431 was extensively metabolized through oxidation to produce various hydroxylated and demethylated species...
November 9, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/29113503/effects-of-crystalline-state-and-self-nanoemulsifying-drug-delivery-system-snedds-on-oral-bioavailability-of-the-novel-anti-hiv-compound-6-benzyl-1-benzyloxymethyl-5-iodouracil-in-rats
#12
Ying-Yuan Lu, Wen-Bing Dai, Xin Wang, Xiao-Wei Wang, Jun-Yi Liu, Pu Li, Ya-Qing Lou, Chuang Lu, Qiang Zhang, Guo-Liang Zhang
The objective of this study was to investigate the effect of crystalline state and a formulation of self-nanoemulsifying drug delivery system (SNEDDS) on oral bioavailability of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W-1), a novel non-nucleoside reverse transcriptase inhibitor, in rats. The crystalline states of W-1 were characterized by scanning electron microscope (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). The SNEDDS was formulated by medium-chain lipids, characterized by droplet particle size...
November 8, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29111882/depletion-of-tylosin-residues-in-feathers-muscle-and-liver-from-broiler-chickens-after-completion-of-antimicrobial-therapy
#13
Javiera Cornejo, Ekaterina Pokrant, Carolina Carvallo, Aldo Maddaleno, Betty San Martín
Tylosin is one of the most commonly used antimicrobial drugs from the macrolide family and in broiler chickens it is used specially for the treatment of infectious pathologies. The poultry industry produces several by-products, among which feathers account for up to 7 percent of a chicken's live weight, thus they amount to a substantial mass across the whole industry. Feathers have been repurposed as an animal feed ingredient by making them feather meal. Therefore, the presence of high concentrations of residues from antimicrobial drugs in feathers might pose a risk to global public health, due to re-entry of these residues into the food chain...
November 7, 2017: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
https://www.readbyqxmd.com/read/29110351/posaconazole-liquid-vs-tablet-formulation-in-lung-transplant-recipients
#14
D Telzer, A Weber, F Ihle, S Matthes, F Ceelen, G Zimmermann, N Kneidinger, R Schramm, H Winter, M Zoller, M Vogeser, J Behr, C Neurohr
BACKGROUND: Posaconazole is an extended-spectrum triazole antifungal used in the treatment and prophylaxis of Aspergillus infections. It is available as oral suspension (POS-Liq) and delayed-release tablets (POS-Tab). OBJECTIVES: The aim of this longitudinal, retrospective study was to compare the clinical effectiveness, toxicity, and pharmacokinetics of POS-Liq vs. POS-Tab in lung transplant recipients (LTx-recipients), who were treated with both formulations subsequently...
November 6, 2017: Mycoses
https://www.readbyqxmd.com/read/29108729/-liquid-crystalline-systems-based-on-glyceryl-monooleate-and-penetration-enhancers-for-skin-delivery-of-celecoxib-characterization-in-vitro-drug-release-and-in-vivo-studies
#15
Mariane de Cássia Lima Dante, Livia Neves Borgheti-Cardoso, Marcia Carvalho de Abreu Fantini, Fabíola Silva Garcia Praça, Wanessa Silva Garcia Medina, Maria Bernadete Riemma Pierre, Marilisa Guimarães Lara
Celecoxib (CXB) is a widely used anti-inflammatory drug that also acts as a chemopreventive agent against several types of cancer, including skin cancer. As the long-term oral administration of CXB has been associated with severe side effects, the skin delivery of this drug represents a promising alternative for the treatment of skin inflammatory conditions and/or chemoprevention of skin cancer. We prepared and characterized liquid crystalline systems based on glyceryl monooleate (GMO) and water containing penetration enhancers which were primarily designed to promote skin delivery of CXB...
November 3, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29105796/penetration-and-pharmacokinetics-of-non-steroidal-anti-inflammatory-drugs-in-rat-prostate-tissue
#16
Venkata K Yellepeddi, Jayashree Radhakrishnan, Rajan Radhakrishnan
BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) involves inflammation of the prostate and affects the quality of life of men of all ages. It is well reported in clinical studies that the treatment for CP/CPPS using nonsteroidal anti-inflammatory drugs (NSAIDs) produced favorable outcomes. However, currently, there are no guidelines on choice of the NSAIDs for the treatment of CP/CPPS. Therefore, in the current research study, we evaluated the prostate tissue penetration of four NSAIDs in rats to provide guidance on choice of NSAIDs for the treatment of CP/CPPS...
November 6, 2017: Prostate
https://www.readbyqxmd.com/read/29104273/study-of-absorption-characteristics-of-the-total-saponins-from-radix-ilicis-pubescentis-in-an-in-situ-single-pass-intestinal-perfusion-spip-rat-model-by-using-ultra-performance-liquid-chromatography-uplc
#17
Guojun Kuang, Huan Yi, Mingjuan Zhu, Jie Zhou, Xueying Shang, Zhongxiang Zhao, Chenchen Zhu, Qiongfeng Liao, Shixia Guan, Lei Zhang
In contrast to the extensively reported therapeutic activities, far less attention has been paid to the intestinal absorption of the total saponins from Radix Ilicis Pubescentis (in Chinese Mao-Dong-Qing, MDQ). This study aimed to investigate the intestinal absorption characteristics of ilexgenin A (C1), ilexsaponin A1 (C2), ilexsaponin B1 (C3), ilexsaponin B2 (C4), ilexsaponin B3 (DC1), and ilexoside O (DC2) when administrated with the total saponins from MDQ (MDQ-TS). An UPLC method for simultaneous determination of C1, C2, C3, C4, DC1, and DC2 in intestinal outflow perfusate was developed and validated...
November 1, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29099714/-biologically-active-alkaloids-from-rhizomes-with-roots-of-vinca-herbacea-waldst-et-kit-growing-in-georgia
#18
V Vachnadze, N Vachnadze, N Gogitidze, N Mushkiashvili, K Mchedlidze
Roots and rhizomes of Vinca herbacea Waldst. et Kit, were collected during early flowering and fruiting. Рhenophases biologically active substances I and II were obtained by liquid-liquid extraction. Dominant alkaloids: tabersonin, reserpine, maidine, norfluorocurarin and copsinin were obtained after the dispertion in citrare-phosfhate buffer and subsequent TLC. Accelerated restitution of granulocytopoiesis was observed in mice during both irradiation and myelotoxic drug-induced acute leucopenia. Increase in total WBC over 200% was observed after treatment by substance I in drug-induced leucopenia model (fivefold oral administration) and over 130% after treatment by substance I in irradiate mice (fivefold intraperitoneal administration)...
October 2017: Georgian Medical News
https://www.readbyqxmd.com/read/29097303/mapping-the-pharmaceutical-design-space-by-amorphous-ionic-liquid-strategies
#19
Johannes Wiest, Marco Saedtler, Anja Balk, Benjamin Merget, Toni Widmer, Heike Bruhn, Marc Raccuglia, Elbast Walid, Franck Picard, Helga Stopper, Wolfgang Dekant, Tessa Lühmann, Christoph Sotriffer, Bruno Galli, Ulrike Holzgrabe, Lorenz Meinel
Poor water solubility of drugs fuels complex formulations and jeopardizes patient access to medication. Simplifying these complexities we systematically synthesized a library of 36 sterically demanding counterions and mapped the pharmaceutical design space for amorphous ionic liquid strategies for Selurampanel, a poorly water soluble drug used against migraine. Patients would benefit from a rapid uptake after oral administration to alleviate migraine symptoms. Therefore, we probed the ionic liquids for the flux, supersaturation period and hygroscopicity leading to algorithms linking molecular counterion descriptors to predicted pharmaceutical outcome...
October 31, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29096443/characteristics-of-artemether-loaded-poly-lactic-co-glycolic-acid-microparticles-fabricated-by-coaxial-electrospray-validation-of-enhanced-encapsulation-efficiency-and-bioavailability
#20
Farhana Akbar Mangrio, Pankaj Dwivedi, Shuya Han, Gang Zhao, Dayong Gao, Ting Si, Ronald X Xu
Artemether is one of the most effective drugs for the treatment of chloroquine-resistant and Plasmodium falciparum strains of malaria. However, its therapeutic potency is hindered by its poor bioavailability. To overcome this limitation, we have encapsulated artemether in poly(lactic-co-glycolic) acid (PLGA) core-shell microparticles (MPs) using the coaxial electrospray method. With optimized process parameters including liquid flow rates and applied electric voltages, experiments are systematically carried out to generate a stable cone-jet mode to produce artemether-loaded PLGA-MPs with an average size of 2 μm, an encapsulation efficiency of 78 ± 5...
November 14, 2017: Molecular Pharmaceutics
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