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https://www.readbyqxmd.com/read/29345156/pharmacokinetic-drug-evaluation-of-opicapone-for-the-treatment-of-parkinson-s-disease
#1
M Svetel, A Tomić, N Kresojević, V S Kostić
Opicapone (OPC) is a novel, potent, reversible, and purely peripheral third-generation COMT inhibitor, which provides an enhancement in levodopa (L-Dopa) availability. It represents adjunctive therapy for L-Dopa treated patients with PD and motor fluctuations. Areas covered: The purpose of this study was to evaluate pharmacokinetic of OPC for the treatment of PD. Expert commentary: Oral OPC exhibits linear, dose-dependent absorption. However, following concomitant ingestion of a high-fat, high-calorie meal, the maximum plasma concentration will be decreased...
January 18, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29344140/familial-genetic-tuberous-sclerosis-complex-associated-with-bilateral-giant-renal-angiomyolipoma-a-case-report
#2
Lina Wang, Dawei Ni, Lin Zhong, Jianbo Wang
Tuberous sclerosis complex (TSC) is an autosomal dominant disease involving multiple organs, but there are a limited number of reports on family TSC. In the present report, a case of a 52-year-old female with a familial genetic TSC, associated with bilateral giant renal angiomyolipoma, was described. The mother, second elder brother and daughter of the patient all exhibited TSC, but the clinical manifestations, and therapeutic prognosis between the family members were not the same. The present case report aimed at identifying an effective diagnostic method and treatment through additional study of familial genetic TSC, in order to prolong and improve the quality of life for patients with TSC...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29342447/design-synthesis-and-anticancer-studies-of-novel-aminobenzazolyl-pyrimidines-as-tyrosine-kinase-inhibitors
#3
Rupesh Chikhale, Sonali Thorat, Rajan Kumar Choudhary, Nikhil Gadewal, Pramod Khedekar
Abnormal signalling from the Protein tyrosine kinases (PTKs) like receptor tyrosine kinases and intracellular tyrosine kinases can lead to diseases such as cancer especially non-small cell lung cancer, chronic myeloid leukaemia and gastrointestinal stromal tumours. Various Protein tyrosine kinase inhibitors are available but face poor bioavailability, severe toxicities and recent cases of drug-resistant cancers prompts for development of better drug molecules. In this study we report the design and development of a novel Protein Tyrosine Kinase (PTK) inhibitor on the basis of pharmacophore modelling...
January 4, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29339167/comparison-of-anticoagulant-therapy-for-atrial-fibrillation-novel-oral-anticoagulants-versus-vitamin-k-antagonists
#4
REVIEW
Sean T Chen, Manesh R Patel
In patients with non-valvular atrial fibrillation (NVAF), oral anticoagulation is important for prevention of stroke and systemic embolism (SE). While Vitamin K antagonists (VKAs) have historically been the standard of care, these medications are limited by numerous food and drug interactions with onerous requirements for frequent monitoring and dose adjustments. Over the past decade, several novel oral anticoagulants (NOACs) have been developed to directly inhibit factor IIa/thrombin (dabigatran) or activated factor X (apixaban, rivaroxaban, edoxaban)...
January 12, 2018: Progress in Cardiovascular Diseases
https://www.readbyqxmd.com/read/29333040/pharmacological-screening-of-trachyspermum-ammi-for-antihyperlipidemic-activity-in-triton-x-100-induced-hyperlipidemia-rat-model
#5
Uzma Saleem, Saba Riaz, Bashir Ahmad, Mohammad Saleem
Background: Mortality rate is increasing due to cardiovascular problems throughout the world. These cardiac problems are directly associated with dyslipidemia. Aim: The aim of this study was to evaluate the antihyperlipidemic effect of aqueous extract and methanol extract of Trachyspermum ammi at 1 g/kg, 3 g/kg, and 5 g/kg dose levels in rats. Materials and Methods: For this purpose, 45 male albino rats were used and randomly divided into nine equal groups (n = 5)...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29328026/clinical-efficacy-of-s-adenosylmethionine-in-patients-with-non-alcoholic-steatohepatitis-and-chronic-kidney-disease-i-ii-stage
#6
A Antoniv, N Antofiychuk, T Danylyshina, I Trefanenko, V Shuper
The article presents a theoretical generalization of the results of the clinical efficacy of S-adenosylmethionine in patients with non-alcoholic steatohepatitis (NASH) in comorbidity with obesity and chronic kidney disease (CKD) of the 1st-2nd stages. The objective of the article was to determine the likely effect of S-adenosylmethionine and Meldonium on the clinical course of non-alcoholic steatohepatitis (NASH) and chronic kidney disease (CKD) of the I-II stages. We examined 75 patients with NASH with comorbid obesity I degree and CKD I and II dgrees...
December 2017: Georgian Medical News
https://www.readbyqxmd.com/read/29311069/meropenem-vaborbactam-single-dose-pharmacokinetics-and-safety-in-subjects-with-chronic-renal-impairment
#7
Christopher M Rubino, Sujata M Bhavnani, Jeffery S Loutit, Brooke Lohse, Michael N Dudley, David C Griffith
Vaborbactam is a member of a new class of β-lactamase inhibitors with inhibitory activity against serine carbapenemases (e.g. Klebsiella pneumoniae carbapenemase) that has been developed in combination with meropenem. Pharmacokinetics of the combination were evaluated in 41 subjects with chronic renal impairment in a Phase 1, open-label, single-dose study. Subjects were assigned to one of five groups based on renal function: normal (creatinine clearance ≥90 mL/min), mild (estimated glomerular filtration rate [eGFR] 60-89 mL/min/1...
January 8, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29309319/tranexamic-acid-dosing-for-cardiac-surgical-patients-with-chronic-renal-dysfunction-a-new-dosing-regimen
#8
Angela Jerath, Qi Joy Yang, K Sandy Pang, Nikita Looby, Nathaly Reyes-Garces, Tijana Vasiljevic, Barbara Bojko, Janusz Pawliszyn, Duminda Wijeysundera, W Scott Beattie, Terrence M Yau, Marcin Wąsowicz
BACKGROUND: Tranexamic acid (TXA) is a common antifibrinolytic agent used to minimize bleeding in cardiac surgery. Up to 50% cardiac surgical patients have chronic renal dysfunction (CRD). Optimal dosing of TXA in CRD remains poorly investigated. This is important as TXA is renally eliminated with accumulation in CRD. High TXA doses are associated with postoperative seizures. This study measures plasma TXA concentrations in CRD cardiac surgical patients for pharmacokinetic modeling and dose adjustment recommendations...
January 5, 2018: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29299983/metabolic-enzyme-system-and-transport-pathways-in-chronic-kidney-diseases
#9
Bin Liu, Fangmei Luo, Xiuju Luo, Shaobin Duan, Zhicheng Gong, Jie Peng
BACKGROUND: Chronic kidney disease (CKD), a global public health problem, affects numerous people worldwide, and the prevalence is rising. Results from animal experiments and clinical investigations have demonstrated that drug metabolic enzymes and transporters-mediated non-renal clearance is dramatically impaired in CKD, co-respondent with the alterations in the elimination of metabolized drugs. Accumulated uremic toxins may downregulate or directly inhibit the activity and/or the expression of drug metabolic enzymes and transporters, which may result in unintended alterations of drug exposure and response in cases when drugs dose are not adjusted for the renal dysfunction...
January 3, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29298160/myeloablative-autologous-stem-cell-transplantation-for-severe-scleroderma
#10
RANDOMIZED CONTROLLED TRIAL
Keith M Sullivan, Ellen A Goldmuntz, Lynette Keyes-Elstein, Peter A McSweeney, Ashley Pinckney, Beverly Welch, Maureen D Mayes, Richard A Nash, Leslie J Crofford, Barry Eggleston, Sharon Castina, Linda M Griffith, Julia S Goldstein, Dennis Wallace, Oana Craciunescu, Dinesh Khanna, Rodney J Folz, Jonathan Goldin, E William St Clair, James R Seibold, Kristine Phillips, Shin Mineishi, Robert W Simms, Karen Ballen, Mark H Wener, George E Georges, Shelly Heimfeld, Chitra Hosing, Stephen Forman, Suzanne Kafaja, Richard M Silver, Leroy Griffing, Jan Storek, Sharon LeClercq, Richard Brasington, Mary E Csuka, Christopher Bredeson, Carolyn Keever-Taylor, Robyn T Domsic, M Bashar Kahaleh, Thomas Medsger, Daniel E Furst
BACKGROUND: Despite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma. METHODS: We randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants)...
January 4, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29284530/fimasartan-proteinuria-sustained-reduction-in-comparison-with-losartan-in-diabetic-chronic-kidney-disease-fantastic-study-protocol-for-randomized-controlled-trial
#11
Jang-Young Kim, Jung-Woo Son, Sungha Park, Tea-Hyun Yoo, Yong-Jin Kim, Dong-Ryeol Ryu, Ho Jun Chin
BACKGROUND: Fimasartan is the ninth angiotensin receptor blocker to be developed. However, it has not yet been evaluated for reno-protective effects in hypertensive diabetic chronic kidney disease (CKD). The target blood pressure (BP) for hypertensive diabetic CKD is also a controversial topic. This trial was designed to assess the reno-protective effects of fimasartan compared to those of losartan as a primary outcome. This study also compares the two drugs with regard to cardiovascular and renal outcomes in accordance with target systolic BP (SBP) (as secondary outcomes)...
December 29, 2017: Trials
https://www.readbyqxmd.com/read/29283068/influence-of-genetic-polymorphisms-on-mycophenolic-acid-pharmacokinetics-and-patient-outcomes-in-renal-transplantation
#12
Miao Guo, Zi-Jie Wang, Hai-Wei Yang, Ling Meng, Ruo-Yun Tan, Min Gu, Ji-Fu Wei
Mycophenolic acid (MPA) is an immunosuppressive drug widely used in the treatment of organ transplantation and autoimmune diseases. Pharmacokinetics and pharmacodynamics of MPA varies between individuals, the potential reasons being the genetic polymorphisms in key enzymes, drug transporters and target proteins of MPA, involving uridine diphosphate glucuronosyltransferase enzymes, organic anion transport polypeptides, multidrug resistance-associated protein 2, inosine monophosphate dehydrogenase and others...
December 27, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29276100/revisiting-raas-blockade-in-ckd-with-newer-potassium-binding-drugs
#13
Panagiotis I Georgianos, Rajiv Agarwal
Among patients with proteinuric chronic kidney disease (CKD), current guideline recommendations mandate the use of agents blocking the renin angiotensin aldosterone system (RAAS) as first-line antihypertensive therapy based on randomized trials demonstrating that RAAS inhibitors are superior to other antihypertensive drug classes in slowing nephropathy progression to end-stage renal disease. However, the opportunities for adequate RAAS blockade in CKD are often limited, and an important impediment is the risk of hyperkalemia, especially when RAAS inhibitors are used in maximal doses or are combined...
December 21, 2017: Kidney International
https://www.readbyqxmd.com/read/29275118/rituximab-maintenance-versus-observation-following-abbreviated-induction-with-chemoimmunotherapy-in-elderly-patients-with-previously-untreated-chronic-lymphocytic-leukaemia-cll-2007-sa-an-open-label-randomised-phase-3-study
#14
Caroline Dartigeas, Eric Van Den Neste, Julie Léger, Hervé Maisonneuve, Christian Berthou, Marie-Sarah Dilhuydy, Sophie De Guibert, Stéphane Leprêtre, Marie C Béné, Florence Nguyen-Khac, Rémi Letestu, Florence Cymbalista, Philippe Rodon, Thérèse Aurran-Schleinitz, Jean-Pierre Vilque, Olivier Tournilhac, Béatrice Mahé, Kamel Laribi, Anne-Sophie Michallet, Alain Delmer, Pierre Feugier, Vincent Lévy, Roselyne Delépine, Philippe Colombat, Véronique Leblond
BACKGROUND: Most patients with chronic lymphocytic leukaemia relapse after initial therapy combining chemotherapy with rituximab. We assessed the efficacy and safety of rituximab maintenance treatment versus observation for elderly patients in remission after front-line abbreviated induction by fludarabine, cyclophosphamide, and rituximab (FCR). METHODS: This randomised, open-label, multicentre phase 3 trial at 89 centres in France enrolled treatment-naive and fit patients aged 65 years or older with chronic lymphocytic leukaemia without del(17p)...
December 20, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/29260442/cellular-senescence-in-the-aging-and-diseased-kidney
#15
REVIEW
F A Valentijn, L L Falke, T Q Nguyen, Roel Goldschmeding
The program of cellular senescence is involved in both the G1 and G2 phase of the cell cycle, limiting G1/S and G2/M progression respectively, and resulting in prolonged cell cycle arrest. Cellular senescence is involved in normal wound healing. However, multiple organs display increased senescent cell numbers both during natural aging and after injury, suggesting that senescent cells can have beneficial as well as detrimental effects in organismal aging and disease. Also in the kidney, senescent cells accumulate in various compartments with advancing age and renal disease...
December 19, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/29258368/lisdexamfetamine-chemistry-pharmacodynamics-pharmacokinetics-and-clinical-efficacy-safety-and-tolerability-in-the-treatment-of-binge-eating-disorder
#16
Kristen Ward, Leslie Citrome
The indications for lisdexamfetamine (LDX), a central nervous system stimulant, were recently expanded to include treatment of moderate to severe binge eating disorder (BED). Areas covered: This review aims to describe the chemistry and pharmacology of LDX, as well as the clinical trials investigating the efficacy and safety of this medication for the management of BED. Expert opinion: LDX is the first medication with United States Food and Drug Administration approval for the treatment of BED. It is an inactive prodrug of d-amphetamine that extends the half-life of d-amphetamine to allow for once daily dosing...
January 4, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29250808/safety-and-efficacy-of-sofosbuvir-based-treatment-of-acute-hepatitis-c-in-end-stage-renal-disease-patients-undergoing-haemodialysis
#17
Y L He, S J Yang, C H Hu, J Dong, H Gao, T T Yan, J F Liu, Y Yang, D F Ren, L Zhu, Y R Zhao, T Y Chen
BACKGROUND: Hepatitis C virus (HCV) infection in patients undergoing haemodialysis is prevalent and aggressive. The treatment of chronic hepatitis C has been revolutionised by the advent of direct-acting antivirals (DAAs). However, the safety, efficacy, and tolerance of DAAs in the treatment of acute HCV infection in patients with end-stage renal disease who are on haemodialysis are unknown. AIM: To evaluate the safety and efficacy of sofosbuvir plus daclatasvir in this specific, difficult-to-treat population...
December 18, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29243035/systemic-lupus-erythematosus-and-ocular-involvement-an-overview
#18
REVIEW
Rosanna Dammacco
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease of undefined etiology and with remarkably heterogeneous clinical features. Virtually any organ system can be affected, including the eye. SLE-related eye involvement can be diagnosed in approximately one-third of the patients and is usually indicative of disease activity. An early diagnosis and the adoption of suitable therapeutic measures are necessary to prevent sight-threatening consequences, especially in patients with juvenile SLE. Periocular lesions, such as eyelid involvement and orbital inflammation, are relatively rare and, in case of orbital masses, may require a biopsy control...
December 14, 2017: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/29239000/minimal-physiologically-based-pharmacokinetic-and-drug-drug-disease-interaction-model-of-rivaroxaban-and-verapamil-in-healthy-and-renally-impaired-subjects
#19
Mohamed Ismail, Vincent H Lee, Christina R Chow, Christopher M Rubino
Current dosing recommendations for rivaroxaban advocate dosage reduction in patients with moderate to severe renal impairment and avoidance of concomitant strong inhibitors of CYP3A or P-glycoprotein. However, rivaroxaban dosing in patients with mild renal impairment taking concomitant moderate inhibitors of CYP3A and P-glycoprotein is not addressed. To quantify the impacts of concomitant verapamil administration and renal impairment on rivaroxaban pharmacokinetics, a minimal physiologically based pharmacokinetic model system was developed and used to evaluate potential increases in rivaroxaban exposure and the consequent increase in risk of major bleeding...
December 14, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29237802/phase-1-dose-escalation-study-of-anti-ctla-4-antibody-ipilimumab-and-lenalidomide-in-patients-with-advanced-cancers
#20
Divya Sakamuri, Isabella C Glitza, Sonia L Betancourt Cuellar, Vivek Subbiah, Siqing Fu, Apostolia M Tsimberidou, Jennifer J Wheler, David S Hong, Aung Naing, Gerald S Falchook, Michelle A Fanale, Maria E Cabanillas, Filip Janku
Preclinical data suggest that combining a check point inhibition with immunomodulatory derivative can increase anticancer response. We designed a dose escalation study using a 3+3 design to determine the safety, maximum tolerated dose (MTD) or recommended phase 2 dose (R2PD) and dose limiting toxicities (DLT) of the anti-CTLA-4 antibody ipilimumab (1.5-3mg/kg intravenously every 28 days x 4) and lenalidomide (10-25mg orally daily for 21 of 28 days until disease progression or unacceptable toxicity) in advanced cancers...
December 13, 2017: Molecular Cancer Therapeutics
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