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Pharmacodynamic

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https://www.readbyqxmd.com/read/27922745/optimization-of-linezolid-treatment-regimens-for-gram-positive-bacterial-infections-based-on-pharmacokinetic-pharmacodynamic-analysis
#1
Minjie Yang, Jing Zhang, Yuancheng Chen, Xiaoyu Liang, Yan Guo, Jicheng Yu, Demei Zhu, Yingyuan Zhang
AIM: To optimize linezolid treatment regimens for Gram-positive bacterial infections based on pharmacokinetic/pharmacodynamic analysis. MATERIALS & METHODS: The minimum inhibitory concentration (MIC) distribution of 572 Gram-positive strains from patients with clinically confirmed infections was analyzed. Using the Monte Carlo simulation method, the cumulative fraction of response and probability of target attainment were determined for linezolid regimens of 600 mg q...
December 6, 2016: Future Microbiology
https://www.readbyqxmd.com/read/27922541/effects-of-the-5-ht1a-receptor-agonists-buspirone-and-8-oh-dpat-on-pupil-size-in-common-marmosets
#2
Manato Kotani, Naoko Urushino, Itaru Natsutani, Yuji Ogi, Kazuhito Ikeda
As pupil size is affected by psychotropic drugs in all mammals, it has been used as a well-established clinical indicator for the preclinical and clinical development of novel drugs. It has been reported that activation of the serotonin (5-HT)1A receptor differently affects pupil response in rodents (mydriasis) and humans (miosis). Thus, it is important to establish a quantitative system for measuring pupil size using other species, such as nonhuman primates. Common marmosets have recently attracted a great deal of attention as suitable experimental animals in the psychoneurological field because of handling ease compared with other nonhuman primates and the requirement for small amounts of test drugs...
December 2, 2016: Behavioural Pharmacology
https://www.readbyqxmd.com/read/27922280/ganetespib-for-small-cell-lung-cancer
#3
Deepa S Subramaniam, Eiran A Warner, Giuseppe Giaccone
Heat shock proteins (Hsps) are part of a complex network of chaperone proteins that are critically involved in the conformational maturation of intracellular proteins and regulate their degradation via the proteasome system Hsps (especially Hsp70 and Hsp90) are upregulated in many cancers and are potentially attractive therapeutic targets. Ganetespib is a potent non-geldanamycin analogue, and avoids the toxicities associated with older analogues due to its small molecular weight, lipophilicity and the absence of the benzoquinone moiety; strong pre-clinical data support its evaluation in lung cancer, especially small cell lung cancer (SCLC)...
December 6, 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27922194/pharmacodynamic-response-profiles-of-anxiolytic-and-sedative-drugs
#4
Xia Chen, Freerk Broeyer, Marieke de Kam, Joke Baas, Adam Cohen, Joop van Gerven
INTRODUCTION: Centrally-acting acutely anxiolytic drugs, like benzodiazepines, barbiturates and gabapentinoids, affect various central nervous system (CNS) functions, which reflect not only their anxiolytic effects but also neuropsychological side-effects. To validate the pharmacodynamic biomarkers for GABA-ergic anxiolytics, this study determined the pharmacodynamics of two anxiolytics and a non-anxiolytic control and linked them to their anxiolytic and sedative effects, during an anxiety-challenge study day...
December 6, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27922057/antiproliferative-activities-of-amaryllidaceae-alkaloids-from-lycoris-radiata-targeting-dna-topoisomerase-i
#5
Gui-Lin Chen, Yong-Qiang Tian, Jian-Lin Wu, Na Li, Ming-Quan Guo
Crude Amaryllidaceae alkaloids (AAs) extracted from Lycoris radiata are reported to exhibit significant anti-cancer activity. However, the specific alkaloids responsible for the pharmacodynamic activity and their targets still remain elusive. In this context, we strived to combine affinity ultrafiltration with topoisomerase I (Top I) as a target enzyme aiming to fish out specific bioactive AAs from Lycoris radiata. 11 AAs from Lycoris radiata were thus screened out, among which hippeastrine (peak 5) with the highest Enrichment factor (EF) against Top I exhibited good dose-dependent inhibition with IC50 at 7...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27921195/new-developments-in-the-pharmacodynamics-and-pharmacokinetics-of-combination-of-chinese-medicine-and-western-medicine
#6
REVIEW
Di Liu, Xiao-Chun Liang
It is very common to use Chinese medicine (CM) combined with Western medicine (WM) in clinical practice. The appropriate combination of CM with WM can reduce toxicity and enhance effects in order to make the best use of advantages and bypass the disadvantages. However, an inappropriate combination can not only affect the curative effect but even cause death. Therefore, strengthening the complementary advantages of the CM and WM to improve the therapeutic efficacy and reduce side effects has become an important research topic of clinical medicine and pharmacy...
December 5, 2016: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/27919627/randomized-phase-2-trial-of-pharmacodynamic-separation-of-pemetrexed-and-intercalated-erlotinib-versus-pemetrexed-alone-for-advanced-nonsquamous-non-small-cell-lung-cancer
#7
Tianhong Li, Bilal Piperdi, William V Walsh, Mimi Kim, Laurel A Beckett, Rasim Gucalp, Missak Haigentz, Venu G Bathini, Huiyu Wen, Kaili Zhou, Patricia B Pasquinelli, Srikanth Gajavelli, Meera Sreedhara, Xianhong Xie, Primo N Lara, David R Gandara, Roman Perez-Soler
BACKGROUND: Pharmacodynamic separation of pemetrexed and erlotinib avoids negative cellular interactions and results in antitumor synergy in erlotinib-resistant non-small-cell lung cancer (NSCLC) cells, independent of EGFR (epidermal growth factor receptor) genotype. PATIENTS AND METHODS: Patients with platinum-treated metastatic nonsquamous NSCLC were randomly assigned 1:2 to pemetrexed alone (500 mg/m(2) provided intravenously on day 1) or pemetrexed followed by erlotinib (150 mg provided orally once daily on days 2-17) every 21 days...
October 28, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27918198/ppar%C3%AE-dependent-increase-of-mouse-urine-output-by-gemfibrozil-and-fenofibrate
#8
Danjun Song, Min Luo, Manyun Dai, Shizhong Bu, Weihua Wang, Burong Zhang, Frank J Gonzalez, Aiming Liu
While gemfibrozil and fenofibrate are prescribed for anti-dyslipidemia treatment, a rational basis for the use of these drugs for treatment of dyslipidemia with concurrent metabolic syndrome has not been established. In this study, wild-type and Pparα-null mice were fed gemfibrozil- or fenofibrate-containing diets for 14 days. Urine output (24 h) was monitored, and urine, serum, and liver and kidney tissues were subjected to toxicity assessment. A 2-month challenge followed by a 2-week wash-out was performed for gemfibrozil to determine urine output and the potential toxicity...
September 6, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27917707/management-of-pneumonia-in-the-pediatric-critical-care-unit-an-area-for-antimicrobial-stewardship
#9
Aimee M Dassner, David P Nicolau, Jennifer E Girotto
Pediatric pneumonia is one of the most common causes of childhood infection requiring hospitalization and is a substantial driver of antimicrobial use among hospitalized children. About 12-20% of pediatric patients hospitalized with community-acquired pneumonia (CAP) require critical care. Additionally, nosocomial pneumonias (i.e. hospital-acquired and ventilator-associated pneumonias) are responsible for 15-53% of hospital-associated infections and are the most common indication for empiric antibiotics in the pediatric intensive care unit...
December 4, 2016: Current Pediatric Reviews
https://www.readbyqxmd.com/read/27917692/once-daily-high-dose-tigecycline-pharmacokinetic-pharmacodynamic-based-dosing-for-optimal-clinical-effectiveness-dosing-matters-revisited
#10
Burke A Cunha, Jeffrey Baron, Cheston B Cunha
Tigecycline has emerged as first line therapy for serious systemic infections due to important pathogens (except P. aeruginosa and Proteus sp.), including multi-drug resistant (MDR) and Gram negative bacilli (GNB), including carbapenem resistant Enterobacteriae. Tigecycline has a "low resistance potential," is protective against C. difficile, and is often the only antibiotic effective against MDR GNB, e.g., Klebsiella sp. Areas covered: Standard dose tigecycline therapy has been used for intra-abdominal infections, complicated skin/skin structure infections (cSSSIs), and CAP...
December 3, 2016: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/27917685/phosphodiesterase-10-inhibitors-in-clinical-development-for-cns-disorders
#11
Hugo Geerts, Athan Spiros, Patrick Roberts
Phosphodiesterase 10 inhibitors (PDE10-I), are conceptually attractive drugs with a potential great therapeutic window as their enriched striatal localization may likely stimulate D1R and reduce D2R downstream effects. However, so far selective PDE10-I with efficacy in animal models have not shown benefit in clinical trials and unexpectedly revealed a substantial dyskinesia motor side-effect. Areas covered: This paper reviews the underlying biological rationale of PDE10 as a target in schizophrenia, Parkinson's and Huntington's disease based on peer-reviewed published articles, the status of the different PDE10-I in clinical development for various CNS indications and explores possible reasons for the clinical trial failures and translational disconnect...
December 3, 2016: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27917682/the-preclinical-discovery-and-development-of-bortezomib-for-the-treatment-of-mantle-cell-lymphoma
#12
Richard Arkwright, Tri Minh Pham, Jeffrey A Zonder, Q Ping Dou
Introduction- Mantle cell lymphoma (MCL) is an incurable, often aggressive B-cell malignancy. Bortezomib (BTZ), the 20S proteasome inhibitor was originally developed and approved for treatment of relapsed refractory multiple myeloma, and subsequently approved for treatment of MCL. BTZ's single-agent activity induces clinical responses in approximately one-third of relapsed MCL patients. BTZ-containing combination therapies have further improved the quality and duration of clinical responses compared to standard chemotherapies in previously untreated MCL patients...
December 3, 2016: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/27915399/naringenin-interferes-with-the-anti-diabetic-actions-of-pioglitazone-via-pharmacodynamic-interactions
#13
Hiroki Yoshida, Rika Tsuhako, Toshiyuki Atsumi, Keiko Narumi, Wataru Watanabe, Chihiro Sugita, Masahiko Kurokawa
Pioglitazone is a peroxisome proliferator-activated receptor gamma (PPARγ) full agonist and useful for the treatment of type 2 diabetes mellitus. Naringenin is a citrus flavonoid with anti-inflammatory actions, which has been shown to prevent obesity-related diseases and to activate PPARγ. The aim of this study was to investigate whether dietary naringenin affects the actions of pioglitazone. We administered naringenin (100 mg/kg) and pioglitazone (10 mg/kg) to Tsumura Suzuki Obese Diabetes (TSOD) mice for 4 weeks and then conducted an oral glucose tolerance test...
December 3, 2016: Journal of Natural Medicines
https://www.readbyqxmd.com/read/27915331/screening-of-bioactive-ingredients-in-ligusticum-chuanxiong-hort-for-protection-against-myocardial-ischemia
#14
Xu Liu, Xiuzhong Li, Songgang Ji, Xiaobo Cui, Mingchun Li
BACKGROUND/AIMS: To study the spectrum-effect relationship and effective components of Ligusticum Chuanxiong Hort. (LCH) on the protection of canine myocardial ischemia. METHODS: Fingerprint spectrum of LCH extracts was developed using high performance liquid chromatography (HPLC), and a canine model of acute myocardial ischemia was established by ligating the coronary artery. Bivariate correlation analysis and multivariate regression analysis were used to correlate the pharmacodynamics of LCH extract and its common peaks in HPLC...
December 5, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27915083/pharmacodynamic-and-cytogenetic-evaluation-in-cyp2c19-2-and-cyp2c19-3-allelomorphism-in-south-indian-population-with-clopidogrel-therapy
#15
Javeed Ahmad Tantray, K Pratap Reddy, Kaiser Jamil, Y Shiva Kumar
BACKGROUND: Genetic factors play a significant role in pathogenesis of most diseases of heart. The present study was undertaken to correlate coronary artery disease with demographical, biochemical alterations, SNPs, gene expression and chromosomal abnormalities and for further enlightening the investigation in this field. METHODS: 150 patients taking clopidogrel drug were selected and single nucleotide polymorphism was done by PCR-RFLP techniques. With the same patients cytogenetic analysis was carried out on leukocyte cultures by karyotyping...
November 11, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27914534/novel-revelation-of-warfarin-resistant-mechanism-in-roof-rats-rattus-rattus-using-pharmacokinetic-pharmacodynamic-analysis
#16
Kazuki Takeda, Yoshinori Ikenaka, Tsutomu Tanikawa, Kazuyuki D Tanaka, Shouta M M Nakayama, Hazuki Mizukawa, Mayumi Ishizuka
Roof rats (Rattus rattus) live mainly in human habitats. Heavy use of rodenticides, such as warfarin, has led to the development of drug resistance, making pest control difficult. There have been many reports regarding mutations of vitamin K epoxide reductase (VKOR), the target enzyme of warfarin, in resistant rats. However, it has been suggested there are other mechanisms of warfarin resistance. To confirm these possibilities, closed colonies of warfarin-susceptible roof rats (S) and resistant rats from Tokyo (R) were established, and the pharmacokinetics/pharmacodynamics of warfarin in rats from both colonies was investigated...
November 2016: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/27913535/reversing-vitamin-k-antagonists-making-the-old-new-again
#17
Sabine Eichinger
Vitamin K antagonists (VKAs) are commonly used for the prevention and treatment of thrombotic disorders. The response to VKAs is highly variable due to their specific interaction with the vitamin K cycle, and hence interference with hepatic synthesis of vitamin K-dependent coagulation factors. Monitoring the anticoagulant effect of VKAs by assessing the patient's international normalized ratio (INR) is essential because complications are closely related to the intensity of anticoagulation. Treatment with VKAs contains a substantial risk of bleeding with a high case fatality rate...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912876/in-vitro-and-ex-vivo-activity-of-an-azadirachta-indica-a-juss-seed-kernel-extract-on-early-sporogonic-development-of-plasmodium-in-comparison-with-azadirachtin-a-its-most-abundant-constituent
#18
Nisha Dahiya, Giuseppina Chianese, Solomon Mequanente Abay, Orazio Taglialatela-Scafati, Fulvio Esposito, Giulio Lupidi, Massimo Bramucci, Luana Quassinti, George Christophides, Annette Habluetzel, Leonardo Lucantoni
BACKGROUND: NeemAzal(®) (NA) is a quantified extract from seed kernels of neem, Azadirachta indica A.Juss. (Meliaceae), with a wide spectrum of biological properties, classically ascribed to its limonoid content. NA contains several azadirachtins (A to L), azadirachtin A (AzaA) being its main constituent. AzaA has been shown to inhibit microgamete formation of the rodent malaria parasite Plasmodium berghei, and NA was found to completely inhibit the transmission of Plasmodium berghei to Anopheles stephensi mosquitoes when administered to gametocytemic mice at a corresponding AzaA dose of 50mg/kg before exposure to mosquitoes...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27912846/new-insights-and-evolving-role-of-pegylated-liposomal-doxorubicin-in-cancer-therapy
#19
REVIEW
Alberto A Gabizon, Yogita Patil, Ninh M La-Beck
We herein review various pharmacological and clinical aspects of pegylated liposomal doxorubicin (PLD), the first nanomedicine to be approved for cancer therapy, and discuss the gap between its potent antitumor activity in preclinical studies and its comparatively modest achievements in clinical studies and limited use in clinical practice. PLD is a complex formulation of doxorubicin based on pharmaceutical nanotechnology with unique pharmacokinetic and pharmacodynamic properties. Its long circulation time with stable retention of the payload and its accumulation in tumors with high vascular permeability both result in important advantages over conventional chemotherapy...
November 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27910712/development-of-a-nanogel-formulation-for-transdermal-delivery-of-tenoxicam-a-pharmacokinetic-pharmacodynamic-modeling-approach-for-quantitative-prediction-of-skin-absorption
#20
Mohammed H Elkomy, Shahira F El Menshawe, Hussein M Eid, Ahmed M A Ali
This study investigates potentials of solid lipid nanoparticles (SLN) based gel for transdermal delivery of tenoxicam (TNX) and describes a pharmacokinetics-pharmacodynamics (PK-PD) modeling approach for predicting concentration-time profile in skin. A 2(3) factorial design was adopted to study the effect of formulation factors on SLN properties and determine the optimal formulation. SLN-gel tolerability was investigated using rabbit skin irritation test. Its anti-inflammatory activity was assessed by carrageenan induced rat paw edema test...
December 2, 2016: Drug Development and Industrial Pharmacy
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