Read by QxMD icon Read


Barbara Wiśniowska, Sebastian Polak
The current study is an example of drug-disease interaction modeling where a drug induces a condition which can affect the pharmacodynamics of other concomitantly taken drugs. The electrophysiological effects of hypokaliemia and heart rate changes induced by the antiasthmatic drugs were simulated with the use of the cardiac safety simulator. Biophysically detailed model of the human cardiac physiology-ten Tusscher ventricular cardiomyocyte cell model-was employed to generate pseudo-ECG signals and QTc intervals for 44 patients from four clinical studies...
March 15, 2018: Journal of Pharmacokinetics and Pharmacodynamics
D Czock, V Schwenger, D Kindgen-Milles, M Joannidis, S John, M Schmitz, A Jörres, A Zarbock, M Oppert, J T Kielstein, C Willam
BACKGROUND: Many anti-infective drugs require dose adjustments in critically ill patients with acute kidney injury (AKI) and renal replacement therapy, in order to achieve adequate therapeutic drug concentrations. OBJECTIVES: The fundamental pharmacokinetic and pharmacodynamic principles of drug dose adjustment are presented. Recommendations on anti-infective drug dosage in intensive care are provided. MATERIALS AND METHODS: We established dose recommendations of selected anti-infective drugs based on information in the summary of product characteristics, published studies and recommendations, pharmacokinetic and pharmacodynamic considerations, and the experience and expert opinion of the authors...
March 15, 2018: Medizinische Klinik, Intensivmedizin und Notfallmedizin
Konstantinos H Katsanos, Konstantinos Papamichael, Joseph D Feuerstein, Dimitrios K Christodoulou, Adam S Cheifetz
The pharmacological management of inflammatory bowel disease (IBD) over the last two decades has transitioned from reliance on aminosalycilates, corticosteroids and immunomodulators to earlier treatment with anti-tumor necrosis factor (anti-TNF) therapy. Nevertheless, 20-30% of patients discontinue anti-TNF therapy for primary non-response and another 30-40% for losing response within one year of treatment. These undesirable therapeutic outcomes can be attributed to pharmacokinetic (anti-drug antibodies and/or low drug concentrations) or pharmacodynamic issues characterized by a non-TNF driven inflammation...
March 12, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Glenn A Jacobson, Sharanne Raidal, Kate Robson, Christian K Narkowicz, David S Nichols, E Haydn Walters
BACKGROUND: Salmeterol (a long acting beta2-agonist) is a chiral molecule. (RR)-salmeterol is responsible for pharmacological effect, but basic knowledge of enantioselective pulmonary pharmacodynamics and pharmacokinetics of salmeterol remains unknown. There are safety concerns with (S)-enantiomers of beta2-agonists, with suggestions that these enantiomers may increase bronchial hyperresponsivneness in asthma patients. METHODOLOGY: Horses (n = 12) received racemic (rac-) salmeterol 250 μg via inhalation...
February 23, 2018: Journal of Pharmaceutical and Biomedical Analysis
Y Dargaud, X Delavenne, D P Hart, S Meunier, P Mismetti
Over the past decades, haemophilia management has continually evolved, with prophylaxis now considered the treatment of choice. Prophylaxis primarily seeks to prevent bleeding and haemarthrosis episodes from occurring and avert the otherwise inevitable haemophilic arthropathy. Yet, numerous unanswered issues remain. These concern dose levels, dosing intervals, ways of integrating variability in bleeding phenotype, patient age, joint status, lifestyle, physical activity, treatment adherence and individual responses to FVIII or FIX concentrates...
March 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
Daniel Geh, Caroline Gordon
Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease. There are three drugs licensed for the treatment of lupus: corticosteroids, hydroxychloroquine and belimumab. Immunosuppressants such as azathioprine, methotrexate and mycophenolate are also used. Despite these treatments there is still considerable morbidity. New treatments are needed for the management of active lupus. Epratuzumab a humanized IgG1 monoclonal antibody that targets CD22 resulting in selective B cell modulation that has been considered a potential treatment for SLE...
March 15, 2018: Expert Review of Clinical Immunology
Dominique Douguet
Presented here are several data sets that gather information collected from the labels of the FDA approved drugs: their molecular structures and those of the described active metabolites, their associated pharmacokinetics and pharmacodynamics data, and the history of their marketing authorization by the FDA. To date, 1852 chemical structures have been identified with a molecular weight less than 2000 of which 492 are or have active metabolites. To promote the sharing of data, the original web server was upgraded for browsing the database and downloading the data sets (http://chemoinfo...
March 8, 2018: ACS Medicinal Chemistry Letters
Kentaro Ando, Yuji Nakamura, Mihoko Hagiwara-Nagasawa, Hiroyuki Harada, Hiroyoshi Miyamoto, Naoki Inamura, Kan Takagi, Ai Goto, Koki Chiba, Nur Jaharat Lubna, Hiroko Izumi-Nakaseko, Atsuhiko T Naito, Atsushi Sugiyama
In order to better understand the variability of pharmacodynamic and pharmacokinetic profiles of terfenadine between the previous studies as well as to qualitatively and quantitatively examine the proarrhythmic potential of its major active metabolite fexofenadine in comparison with that of terfenadine, we directly compared their electropharmacological effects with halothane-anesthetized dogs (n = 3). For this purpose, we adopted a cross-over design, which can directly compare the effects of terfenadine and fexofenadine under the identical metabolic condition...
2018: Journal of Toxicological Sciences
Johann Bartko, Christian Schoergenhofer, Michael Schwameis, Patricia Wadowski, Jacek Kubica, Bernd Jilma, Eva-Luise Hobl
Aspirin is a cornerstone in the anti-platelet therapy of acute coronary syndromes. Co-administration of morphine may potentially influence the intestinal absorption, pharmacokinetics and pharmacodynamics as seen with P2Y12-inhibitors. In this trial, healthy volunteers were randomized to receive morphine (5 mg, iv bolus injection) at one of 7 different time points before, after or with aspirin (162 mg, po) in a double-blind, placebo controlled fashion. After a 14-day washout, subjects received placebo instead of morphine...
March 14, 2018: Journal of Pharmacology and Experimental Therapeutics
Guozhi Yu, Desiree Y Baeder, Roland R Regoes, Jens Rolff
Antibiotic resistance constitutes one of the most pressing public health concerns. Antimicrobial peptides (AMPs) of multicellular organisms are considered part of a solution to this problem, and AMPs produced by bacteria such as colistin are last-resort drugs. Importantly, AMPs differ from many antibiotics in their pharmacodynamic characteristics. Here we implement these differences within a theoretical framework to predict the evolution of resistance against AMPs and compare it to antibiotic resistance. Our analysis of resistance evolution finds that pharmacodynamic differences all combine to produce a much lower probability that resistance will evolve against AMPs...
March 14, 2018: Proceedings. Biological Sciences
Leandro Nóbrega, Ricardo Jorge Dinis-Oliveira
New psychoactive substances (NPS), often referred as 'legal highs' or 'designer drugs', are derivatives and analogs of existing psychoactive drugs that are introduced in the recreational market to circumvent existing legislation on drugs of abuse. This work aims to review the state-of-the-art regarding chemical, molecular pharmacology, and in vitro and in vivo data on toxicokinetics of the potent synthetic cathinone α-pyrrolidinovalerophenone (α-PVP or flakka or zombie drug). Chemical, pharmacological, toxicological, and clinical effects of α-PVP were searched in PubMed (U...
March 14, 2018: Drug Metabolism Reviews
Katherine Plewes, Hugh W F Kingston, Aniruddha Ghose, Thanaporn Wattanakul, Md Mahtab Uddin Hassan, Md Shafiul Haider, Prodip K Dutta, Md Akhterul Islam, Shamsul Alam, Selim Md Jahangir, A S M Zahed, Md Abdus Sattar, M A Hassan Chowdhury, M Trent Herdman, Stije J Leopold, Haruhiko Ishioka, Kim A Piera, Prakaykaew Charunwatthana, Kamolrat Silamut, Tsin W Yeo, Sue J Lee, Mavuto Mukaka, Richard J Maude, Gareth D H Turner, Md Abul Faiz, Joel Tarning, John A Oates, Nicholas M Anstey, Nicholas J White, Nicholas P J Day, Md Amir Hossain, L Jackson Roberts, Arjen M Dondorp
Background: Acute kidney injury independently predicts mortality in falciparum malaria. It is not known whether acetaminophen's capacity to inhibit plasma hemoglobin-mediated oxidation is renoprotective in severe malaria. Methods: A phase 2, open-label, randomized controlled trial at two hospitals in Bangladesh was conducted to assess effects on renal function, safety, pharmacokinetic properties and pharmacodynamic effects of acetaminophen. Febrile patients ( >12 years) with severe and moderately severe falciparum malaria were randomly assigned to receive acetaminophen (1g 6-hourly for 72 hours) or no acetaminophen, as an adjunct to intravenous artesunate...
March 12, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Mary B Wire, Xiaobin Li, Jianping Zhang, William Sallas, Vassilios Aslanis, Taoufik Ouatas
Our objective was to support initial eltrombopag doses and dose titration based on modeling and simulation of plasma exposure and platelet count response in pediatric patients aged 1-17 years with previously treated chronic immune thrombocytopenia enrolled in 2 clinical studies. Data from 168 pediatric patients were used to develop a life-span population pharmacokinetic and pharmacodynamic model including 3 pharmacokinetic and 4 pharmacodynamic compartments enabling simulation of platelet counts for various starting doses and dose titration schedules...
March 14, 2018: Clinical Pharmacology and Therapeutics
Ippei Ikushima, Lene Jensen, Anne Flint, Tomoyuki Nishida, Jeppe Zacho, Shin Irie
INTRODUCTION: Semaglutide is a glucagon-like peptide-1 analogue for once-weekly subcutaneous treatment of type 2 diabetes. This trial compared the pharmacokinetics, pharmacodynamics, and safety of semaglutide in Japanese and Caucasian subjects. METHODS: In this single-center, double-blind, parallel-group, 13-week trial, 44 healthy male subjects (22 Japanese, 22 Caucasian) were randomized within each race to semaglutide 0.5 mg (n = 8), 1.0 mg (n = 8), placebo 0...
March 13, 2018: Advances in Therapy
Sanjay Kalra
This communication reviews available high concentration insulins and their basic as well as clinical pharmacology. It classifies all high concentration insulins, and describes their pharmacokinetic and pharmacodynamic properties. The article discusses the utility of high concentrations insulins, lists indications for these preparations, highlights caveats for their safe use, and proposes pragmatic contraindications to their prescription.
January 2018: Indian Journal of Endocrinology and Metabolism
Chrysovalantou Mihailidou, Pavlos Papakotoulas, Athanasios G Papavassiliou, Michalis V Karamouzis
Ciclopirox olamine (CPX) is an antifungal agent that has recently demonstrated promising anti-neoplastic activity against hematologic and solid tumors. Here, we evaluated CPX compared with gemcitabine alone as well as their combination in human pancreatic cancer cell lines; BxPC-3, Panc-1, and MIA PaCa-2 and in humanized xenograft mouse models. We also examined the preclinical pharmacodynamic activity of CPX. CPX caused a pronounced decrease in cell proliferation and clonogenic growth potential. These inhibitory effects were accompanied by induction of reactive oxygen species (ROS), which were strongly associated with reduced Bcl-xL and survivin levels and activation of a panel of caspases, especially caspase-3, and finally resulted in apoptotic death...
February 13, 2018: Oncotarget
Eduardo Méndez, Cristina P Rodriguez, Micheal Kao, Sharat C Raju, Ahmed Diab, Richard A Harbison, Eric Q Konnick, Ganesh Mugundu, Rafael Santana-Davila, Renato Martins, Neal D Futran, Laura Q M Chow
PURPOSE: The WEE1 tyrosine kinase regulates G2/M transition and maintains genomic stability, particularly in p53-deficient tumors which require DNA repair after genotoxic therapy. There is a need to exploit the role of WEE1 inhibition in head and neck squamous cell carcinoma (HNSCC) mostly driven by tumor-suppressor loss. This completed phase I clinical trial represents the first published clinical experience using the WEE1 inhibitor, AZD1775, with cisplatin and docetaxel. EXPERIMENTAL DESIGN: We implemented an open-label phase I clinical trial using a 3+3 dose-escalation design for patients with Stage III/IVB HNSCC with borderline-resectable or unresectable disease, who were candidates for definitive chemoradiation...
March 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Luca Mazzarella, Alessandro Guida, Giuseppe Curigliano
Epidermal Growth Factor Receptor (EGFR)-dependent signaling plays a crucial role in epithelial cancer biology, and dictated the development of several targeting agents. The mouse-human chimeric antibody Cetuximab was among the first to be developed. After about two decades of clinical research it has gained a significant place in the management of advanced colorectal and head and neck cancers, whereas its development in non small cell lung cancer (NSCLC) has not led to a place in routine clinical practice, because of marginal clinical benefit despite statistically significant Phase III trials...
March 14, 2018: Expert Opinion on Biological Therapy
Yanhua Hu, Julie A Carman, Deborah Holloway, Selena Kansal, Li Fan, Christine Goldstine, Deborah Lee, John E Somerville, Robert Latek, Robert Townsend, Alyssa Johnsen, Sean Connolly, Somnath Bandyopadhyay, Nancy Shadick, Michael E Weinblatt, Richard Furie, Steven G Nadler
OBJECTIVE: To develop an objective, readily measurable pharmacodynamic biomarker of glucocorticoid (GC) activity. METHODS: Genes modulated by prednisolone were identified from in vitro studies using peripheral blood mononuclear cells from normal healthy volunteers (NHVs). Using the criteria of a >2-fold change relative to vehicle controls and an adjusted P value cutoff of <0.05, 64 upregulated and 18 downregulated genes were identified. A composite score of the upregulated genes was generated using a single-sample gene set enrichment analysis algorithm...
March 13, 2018: Arthritis & Rheumatology
Benjamin Wu, Murad Melhem, Raju Subramanian, Ping Chen, Bethlyn Jaramilla Sloey, Bruno Fouqueray, M Benjamin Hock, Gary L Skiles, Andrew T Chow, Edward Lee
Etelcalcetide, a d-amino acid peptide, is an intravenous calcimimetic approved for the treatment of secondary hyperparathyroidism. Etelcalcetide binds the calcium-sensing receptor and increases its sensitivity to extracellular calcium, thereby decreasing secretion of parathyroid hormone (PTH) by chief cells. Etelcalcetide and its low-molecular-weight transformation products are rapidly cleared by renal excretion in healthy subjects, but clearance is substantially reduced and dependent on hemodialysis in end-stage renal disease...
March 13, 2018: Journal of Clinical Pharmacology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"