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Jens Sandahl Christiansen, Philippe F Backeljauw, Martin Bidlingmaier, Beverly M K Biller, Margaret C S Boguszewski, Felipe F Casanueva, Philippe Chanson, Pierre Chatelain, Catherine S Choong, David R Clemmons, Laurie E Cohen, Pinchas Cohen, Jan Frystyk, Adda Grimberg, Yukihiro Hasegawa, Morey W Haymond, Ken Ho, Andrew R Hoffman, Jeff M P Holly, Reiko Horikawa, Charlotte Höybye, Jens Otto L Jorgensen, Gudmundur Johannsson, Anders Juul, Laurence Katznelson, John J Kopchick, K O Lee, Kuk-Wha Lee, Xiaoping Luo, Shlomo Melmed, Bradley S Miller, Madhusmita Misra, Vera Popovic, Ron G Rosenfeld, Judith Ross, Richard J Ross, Paul Saenger, Christian J Strasburger, Michael O Thorner, Haim Werner, Kevin Yuen
OBJECTIVE: The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). PARTICIPANTS: A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. EVIDENCE: Current literature was reviewed for gaps in knowledge...
June 2016: European Journal of Endocrinology
Manoj Kumar, Sean P Arlauckas, Sona Saksena, Gaurav Verma, Ranjit Ittyerah, Stephen Pickup, Anatoliy V Popov, Edward J Delikatny, Harish Poptani
Abnormal choline metabolism is a hallmark of cancer and is associated with oncogenesis and tumor progression. Increased choline is consistently observed in both preclinical tumor models and in human brain tumors by proton magnetic resonance spectroscopy (MRS). Thus, inhibition of choline metabolism using specific choline kinase inhibitors such as MN58b may be a promising new strategy for treatment of brain tumors. We demonstrate the efficacy of MN58b in suppressing phosphocholine production in three brain tumor cell lines...
April 2015: Molecular Cancer Therapeutics
Patrick L Daly, Richard C Becker
There has been substantial progress toward understanding and investigating the specific genetic factors that influence interindividual variations in platelet-directed therapy. There has also been substantial progress toward better understanding of the pharmacogenetics of drug metabolism and phamacodynamic response to platelet antagonists. We summarize the relationship between genetic polymorphisms, response to platelet antagonists, and clinical impact on patient treatment for the commonly used antiplatelet drugs...
May 2014: Current Atherosclerosis Reports
Peter M Wilson, Melissa J Labonte, Shelby C Martin, Stephanie T Kuwahara, Anthony El-Khoueiry, Heinz-Josef Lenz, Robert D Ladner
Despite compelling preclinical data in colorectal cancer (CRC), the efficacy of HDACIs has been disappointing in the clinic. The goal of this study was to evaluate the effectiveness of vorinostat and panobinostat in a dose- and exposure-dependent manner in order to better understand the dynamics of drug action and antitumor efficacy. In a standard 72 h drug exposure MTS assay, notable concentration-dependent antiproliferative effects were observed in the IC50 range of 1.2-2.8 μmol/L for vorinostat and 5.1-17...
August 2013: Investigational New Drugs
Xiaoling Zheng, Caihong Zheng
OBJECTIVE: To prepare the gel of Chinese medicine catechu,study its release mechanism in vitro and observe the anti-inflammatory activity in rats. METHOD: Using the amount of catechin and epicatechin in dry extract as major evaluation factors, orthogonal experiment was carried out to investigate four influential factors of the ethanol concentration, ratio of raw material to solvent, ultrasonic time and extraction temperature. The catechu gel was prepared by using carbomer-940 as the gel base, and triethanomine as neutralizer...
September 2011: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Gina J Ryan, Yolanda Hardy
WHAT IS KNOWN AND OBJECTIVE: The prevalence of diabetes is increasing worldwide. Over the recent years, new discoveries have led to the development of new pharmacological agents targeting the incretin hormones gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1). These agents, called incretin-mimetics, are the newest agents added to the diabetes treatment options. The purpose of this article is to review the relevant literature on the chemistry, pharmacology, pharmacokinetics, metabolism, clinical trials, safety, drug interactions and place in therapy of liraglutide in the treatment of type 2 diabetes...
June 2011: Journal of Clinical Pharmacy and Therapeutics
Arun Rasheed, C K Ashok Kumar, Ashutosh Mishra
The present investigation deals with the synthesis of novel prodrugs of dexibuprofen with amino acids with an aim to achieve potent anti-inflammatory activity and less gastrointestinal toxicity. Structures of synthesized compounds were confirmed by spectral and elemental analyses. In vitro hydrolytic studies in simulated intestinal fluid, 80% plasma and rat faecal matter showed satisfactory release of dexibuprofen due to enzymatic cleavage. The synthesized prodrugs were evaluated for anti-inflammatory activity, analgesia, ulcerogenicity and histopathology...
October 2011: Journal of Enzyme Inhibition and Medicinal Chemistry
Jamie L McCall, Michael W DeGregorio
IMPORTANCE OF THE FIELD: Millions of women worldwide suffer from vulvovaginal atrophy (VVA) associated with menopause, and many women report that this adversely affects their quality of life. Ospemifene is a non-hormonal estrogen receptor agonist/antagonist effective in the treatment of VVA. Although similar in structure to other estrogen receptor agonists/antagonists that have antagonistic effects on the vagina, ospemifene has an estrogen-like effect on vaginal epithelium. This review focuses on ospemifene including its pharmacologic properties, clinical efficacy and safety...
June 2010: Expert Opinion on Drug Metabolism & Toxicology
Arun Rasheed, C K Ashok Kumar
The gastrointestinal toxicity associated with aceclofenac can be reduced by condensing its carboxylic acid group with methyl esters of amino acids like histidine and alanine to give amide linkage by the Schotten-Baumann method. Physicochemical characterization of the conjugates was carried out by various analytical and spectral methods. The synthesized conjugates were also subjected to in vitro hydrolysis in simulated gastric fluid (SGF) at pH 1.2, simulated intestinal fluid (SIF) at pH 7.4 and SIF+ 80% human plasma at pH 7...
March 2010: Acta Pharmaceutica
Jean-Pierre Valentin, Russell Bialecki, Lorna Ewart, Tim Hammond, Derek Leishmann, Silvana Lindgren, Vicente Martinez, Chris Pollard, Will Redfern, Rob Wallis
This article outlines a strategy for collecting accurate data for the determination of the sensitivity, specificity and predictive value of safety pharmacology models. This entails performing a retrospective analysis on commonly used safety pharmacology endpoints and an objective assessment of new non-clinical models. Such assessments require a systematic quantitative analysis of safety pharmacology parameters as well as clinical Phase I adverse events. Once the sensitivity, specificity and predictive capacity of models have been determined, they can be aligned within specific phases of the drug discovery and development pipeline for maximal impact, or removed from the screening cascade altogether...
September 2009: Journal of Pharmacological and Toxicological Methods
Raewadee Wisedpanichkij, Wanna Chaijaroenkul, Piyanan Sangsuwan, Jintana Tantisawat, Kanyarat Boonprasert, Kesara Na-Bangchang
The treatment and control of malaria is becoming increasingly difficult due to resistance of Plasmodium falciparum strains resistance to commonly used antimalarials. Combination therapy is currently the strategy for combating multi-drug resistant falciparum malaria, through exploiting phamacodynamic synergistic effect and delaying the emergence of drug resistance. The objective of the present study was to investigate antimalarial activity of inhibitors of cytochrome P450 (CYP) enzyme including their interactions with the antimalarial mefloquine against chloroquine-resistant (K1) and chloroquine-sensitive (3D7) P...
October 2009: Acta Tropica
R Cohen
The progress in the knowledge of antibiotic action mechanisms have led to determine phamacodynamic/pharmacokinetic (PK/PD) parameters predictive of antibiotic efficacy in bacterial infections. These parameters could vary according to the antibiotic compound, the bacterial specie implicated, the localization of the infection, the severity of the disease. The serum PK/PD parameters are predictive of efficacy in several infections (respiratory, skin, bone) and become a major criterion for selecting antibiotics in clinical practice...
October 2008: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
Tsukasa Uno, Katsuyoshi Sugimoto, Kazunobu Sugawara, Tomonori Tateishi
Previous studies reported omeprazole to be an inhibitor of cytochrome P450 (CYP) 2C19 and suggested the pharmacokinetic interaction of omeprazole with R-warfarin. The aim of this study was to compare possible effects of omeprazole on the stereoselective pharmacokinetics and pharmacodynamics of warfarin between CYP2C19 genotypes. Seventeen subjects, of whom 10 were homozygous extensive metabolizers (hmEMs) and seven were poor metabolizers (PMs) for CYP2C19, were enrolled in this randomized crossover study, and they ingested 20 mg omeprazole or placebo once daily for 11 days...
June 2008: Therapeutic Drug Monitoring
R Cohen, E Grimprel
The progress in the knowledge of antibiotic action mechanisms have led to determine phamacodynamic/pharmacokinetic (PK/PD) parameters predictive of antibiotic efficacy in bacterial infections. According to the antibiotic compound, the implicated bacterial specie, the localization of the infection, the severity of the disease, these parameters could vary. The PK/PD parameters described in this paper focus only on blood compartment and S. aureus, (main bacteria implicated in bone and joint tissue infections)...
October 2007: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
Manuela Contin, Paolo Martinelli, Roberto Riva, Maurizio Dondi, Stefano Fanti, Cinzia Pettinato, Cesa Scaglione, Fiorenzo Albani, Agostino Baruzzi
Levodopa pharmacokinetic-phamacodynamic (PK-PD) modeling may be able to test the functional integrity of the nigrostriatal dopaminergic system in Parkinson's disease (PD). [(123)I]-FP-CIT SPECT imaging of striatal dopamine transporters has also been introduced for the evaluation of presynaptic dopaminergic homeostasis. We aimed to assess the intrapatient relation between levodopa PK-PD and SPECT measures of dopaminergic function in PD. Thirty-five PD patients, 1 to 4 on the Hoehn and Yahr (H&Y) scale, enrolled in the study...
December 2003: Journal of Neurology
No abstract text is available yet for this article.
March 1952: Comptes Rendus des Séances de la Société de Biologie et de Ses Filiales
Graham C Wong, Robert P Giugliano, Elliott M Antman
CONTEXT: Low-molecular-weight heparins (LMWHs) possess several potential pharmacological advantages over unfractionated heparin as an antithrombotic agent. OBJECTIVE: To systematically summarize the clinical data on the efficacy and safety of LMWHs compared with unfractionated heparin across the spectrum of acute coronary syndromes (ACSs), and as an adjunct to percutaneous coronary intervention (PCI). DATA SOURCES: We searched MEDLINE for articles from 1990 to 2002 using the index terms heparin, enoxaparin, dalteparin, nadroparin, tinzaparin, low molecular weight heparin, myocardial infarction, unstable angina, coronary angiography, coronary angioplasty, thrombolytic therapy, reperfusion, and drug therapy, combination...
January 15, 2003: JAMA: the Journal of the American Medical Association
A U Buzdar
The new generation of selective aromatase inhibitors (anastrozole, letrozole and exemestane) offer a significant efficacy and safety advantage over both older agents in this class (aminoglutethimide) and the progestins (megestrol acetate (MA)), as second-line treatment for postmenopausal women with advanced hormone-dependent breast cancer who have failed on tamoxifen therapy. Exemestane, a steroidal aromatase inhibitor, has been shown to have activity after failure with the non-steroidal aromatase inhibitors, anastrozole and letrozole, and could be used as third-line treatment...
December 2001: Journal of Steroid Biochemistry and Molecular Biology
K A Hope, D E Havrda
OBJECTIVE: To discuss the effect on the international normalized ratio (INR) when patients are converted from therapy with Coumadin to generic warfarin. CASE SUMMARY: Two cases at a family medicine center anticoagulation clinic in Oklahoma City, OK, in which subtherapeutic INR values occurred after a switch from Coumadin to generic warfarin, while all other variables were kept consistent demonstrate the need for close monitoring of the INR when patients are switched between brands of warfarin...
February 2001: Annals of Pharmacotherapy
K E Andersson, C G Persson
The phamacodynamics of theophylline including cardiovascular and renal effects, effects on the CNS, gastrointestinal tract and uterus and the metabolic actions of the drug are reviewed. Emphasis is given to the clinical consequences of these effects.
1980: European Journal of Respiratory Diseases. Supplement
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