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Pharmacokinetics pharmacodynamics

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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
#1
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
https://www.readbyqxmd.com/read/27909995/solithromycin-a-novel-fluoroketolide-for-the-treatment-of-community-acquired-bacterial-pneumonia
#2
REVIEW
George G Zhanel, Erika Hartel, Heather Adam, Sheryl Zelenitsky, Michael A Zhanel, Alyssa Golden, Frank Schweizer, Bala Gorityala, Philippe R S Lagacé-Wiens, Andrew J Walkty, Alfred S Gin, Daryl J Hoban, Joseph P Lynch, James A Karlowsky
Solithromycin is a novel fluoroketolide developed in both oral and intravenous formulations to address increasing macrolide resistance in pathogens causing community-acquired bacterial pneumonia (CABP). When compared with its macrolide and ketolide predecessors, solithromycin has several structural modifications which increase its ribosomal binding and reduce its propensity to known macrolide resistance mechanisms. Solithromycin, like telithromycin, affects 50S ribosomal subunit formation and function, as well as causing frame-shift errors during translation...
December 1, 2016: Drugs
https://www.readbyqxmd.com/read/27909752/erratum-to-a-literature-review-of-the-pharmacokinetics-and-pharmacodynamics-of-dobutamine-in-neonates
#3
Liam Mahoney, Geetika Shah, David Crook, Hector Rojas-Anaya, Heike Rabe
No abstract text is available yet for this article.
December 1, 2016: Pediatric Cardiology
https://www.readbyqxmd.com/read/27908273/pharmacokinetic-and-pharmacodynamic-features-of-nanoemulsion-following-oral-intravenous-topical-and-nasal-route
#4
Hira Choudhury, Bapi Gorain, Bappaditya Chatterjee, Uttam Kumar Mandal, Pinaki Sengupta, Rakesh Kumar Tekade
Most of the active pharmaceutical ingredients discovered recently in pharmaceutical field exhibits poor aqueous solubility that pose major problem in their oral administration. The oral administration of these drugs gets further complicated due to their short bioavailability, inconsistent absorption and inter/intra subject variability. Pharmaceutical emulsion holds a significant place as a primary choice of oral drug delivery system for lipophilic drugs used in pediatric and geriatric patients. Pharmacokinetic studies on nanoemulsion mediated drugs delivery approach indicates practical feasibility in regards to their clinical translation and commercialization...
December 1, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27908266/is-metformin-a-perfect-drug-updates-in-pharmacokinetics-and-pharmacodynamics
#5
Magdalena Markowicz-Piasecka, Kristiina Maria Huttunen, Łukasz Mateusiak, Elżbieta Mikiciuk-Olasik, Joanna Sikora
Metformin, a synthetic biguanide, is currently one of the most frequently recommended medications for type 2 diabetes treatment around the world. In this review, we present the latest discoveries in the pharmacokinetics of metformin, especially the role of transporters (e.g. Organic Cation Transporters OCTs, Multidrug and Toxin Extrusion transporters MATE) in oral absorption, distribution, elimination and biochemical effects of metformin in humans. We also review the associations between genetic variations of metformin transporters, their pharmacokinetics and drug efficacy or drug responses...
December 1, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27907978/comparison-of-the-single-dose-pharmacokinetics-pharmacodynamics-and-safety-of-two-novel-oral-formulations-of-dimethandrolone-undecanoate-dmau-a-potential-oral-male-contraceptive
#6
R Ayoub, S T Page, R S Swerdloff, P Y Liu, J K Amory, A Leung, L Hull, D Blithe, A Christy, J H Chao, W J Bremner, C Wang
Dimethandrolone (DMA, 7α,11β-dimethyl-19-nortestosterone) has both androgenic and progestational activities, ideal properties for a male hormonal contraceptive. In vivo, dimethandrolone undecanoate (DMAU) is hydrolyzed to DMA. We showed previously that single oral doses of DMAU powder in capsule taken with food are well tolerated and effective at suppressing both LH and testosterone (T), but absorption was low. We compared the pharmacokinetics and pharmacodynamics of two new formulations of DMAU, in castor oil and in self-emulsifying drug delivery systems (SEDDS), with the previously tested powder formulation...
December 1, 2016: Andrology
https://www.readbyqxmd.com/read/27907971/-interpretation-of-bacterial-susceptibility-resistance-to-antibiotics
#7
Milan Kolář
Bacterial resistance may be defined from a microbiological, clinical and pharmacological perspective. Microbiological resistance refers to the presence of genetic information coding for the relevant mechanism of resistance of a bacterium to a particular antibiotic. In case of clinical interpretation, breakpoints are of key importance as their role is to distinguish bacterial pathogens in which successful therapy is highly probable from isolates with a high likelihood of failure. However, it is questionable whether this approach is suitable for all patients, particularly those receiving intensive care for life-threatening infections...
September 2016: Klinická Mikrobiologie a Infekc̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27907963/optimizing-medication-outcomes-in-neurocritical-care-focus-on-clinical-pharmacology
#8
Denise H Rhoney, Kathryn Morbitzer, Jimmi Hatton-Kolpek
Drug dosing in neurocritically ill patients presents enormous challenges for clinicians due to the complex pathophysiological alterations. These alterations are dynamic both between and within patients. Unpredictable exposure from standard dosing regimens, which were extrapolated to intensive care unit patients from healthy volunteer studies, may influence medication outcomes. Knowledge of potential alterations in pharmacokinetics/pharmacodynamics in these patients could be applied to maximize the clinical response and minimize adverse effects...
December 2016: Seminars in Neurology
https://www.readbyqxmd.com/read/27906953/what-s-tramadol-got-to-do-with-it-a-case-report-of-rebound-hypoglycemia-a-reappraisal-and-review-of-potential-mechanisms
#9
Charles A Odonkor, Akhil Chhatre
BACKGROUND: Tramadol has gained traction as an analgesic of choice among pain practicing physicians. However some concerns regarding a previously unlabeled adverse reaction - hypoglycemia - have cast it in a dim light. Prior reports have noted an associated risk of hospitalization for hypoglycemia after tramadol use, but whether tramadol is the main causal agent is poorly understood and the underlying mechanisms are not well delineated. We present a unique case of rebound hypoglycemia as a variation of the theme of tramadol's adverse effect profile in a patient with type 1 diabetes mellitus, and reappraise potential mechanisms underlying this underappreciated phenomenon...
November 2016: Pain Physician
https://www.readbyqxmd.com/read/27906418/assessment-of-celecoxib-poly-lactic-co-glycolic-acid-nanoformulation-on-drug-pharmacodynamics-and-pharmacokinetics-in-rats
#10
S Harirforoosh, K O West, D E Murrell, J W Denham, P C Panus, G A Hanley
OBJECTIVE:  Celecoxib (CEL) is a nonsteroidal anti-inflammatory drug (NSAID) showing selective cycloxygenase-2 inhibition. While effective as a pain reducer, CEL exerts some negative influence on renal and gastrointestinal parameters. This study examined CEL pharmacodynamics and pharmacokinetics following drug reformulation as a poly(lactic-co-glycolic) acid nanoparticle (NP). MATERIALS AND METHODS: Rats were administered either vehicle (VEH) (methylcellulose solution), blank NP, 40 mg/kg CEL in methylcellulose, or an equivalent NP dose (CEL-NP)...
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27905678/a-phase-i-ii-trial-of-at9283-a-selective-inhibitor-of-aurora-kinase-in-children-with-relapsed-or-refractory-acute-leukemia-challenges-to-run-early-phase-clinical-trials-for-children-with-leukemia
#11
B Vormoor, G J Veal, M J Griffin, A V Boddy, J Irving, L Minto, M Case, U Banerji, K E Swales, J R Tall, A S Moore, M Toguchi, G Acton, K Dyer, C Schwab, C J Harrison, J D Grainger, D Lancaster, P Kearns, D Hargrave, J Vormoor
Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies...
December 1, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27903151/how-to-manage-the-obese-patient-with-cancer
#12
Andrew G Renehan, Michelle Harvie, Ramsey I Cutress, Michael Leitzmann, Tobias Pischon, Sacha Howell, Anthony Howell
Purpose Obesity (body mass index [BMI] ≥ 30 kg/m(2)) is common among patients with cancer. We reviewed management issues in the obese patient with cancer, focusing on how obesity influences treatment selection (including chemotherapy dosing), affects chemotherapy toxicity and surgical complications, and might be a treatment effect modifier. Methods The majority of evidence is drawn from observational studies and secondary analyses of trial data, typically analyzed in N × 3 BMI categories (normal weight, overweight, and obese) matrix structures...
December 10, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27902884/synthesis-and-biological-evaluation-of-new-triazolo-and-imidazolopyridine-ror%C3%AE-t-inverse-agonists
#13
Samuel Hintermann, Christine Guntermann, Henri Mattes, David A Carcache, Juergen Wagner, Anna Vulpetti, Andreas Billich, Janet Dawson, Klemens Kaupmann, Joerg Kallen, Rowan Stringer, David Orain
Retinoic-acid-related orphan receptor γt (RORγt) is a key transcription factor implicated in the production of pro-inflammatory Th17 cytokines, which drive a number of autoimmune diseases. Despite diverse chemical series having been reported, combining high potency with a good physicochemical profile has been a very challenging task in the RORγt inhibitor field. Based on available chemical structures and incorporating in-house knowledge, a new series of triazolo- and imidazopyridine RORγt inverse agonists was designed...
November 30, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27902848/topiramate-in-migraine-prevention-a-2016-perspective
#14
Stephen D Silberstein
BACKGROUND: In evidence-based guidelines published in 2000, topiramate was a third-tier migraine preventive with no scientific evidence of efficacy; recommendation for its use reflected consensus opinion and clinical experience. Its neurostabilizing activity, coupled with its favorable weight profile, made topiramate an attractive alternative to other migraine preventives that caused weight gain. When guidelines for migraine prevention in episodic migraine were published in 2012, topiramate was included as a first-line option based on double-blind, randomized controlled trials involving nearly 3000 patients...
November 30, 2016: Headache
https://www.readbyqxmd.com/read/27897084/multi-spectroscopic-and-molecular-modeling-studies-of-interaction-between-two-different-angiotensin-i-converting-enzyme-inhibitory-peptides-from-gluten-hydrolysate-and-human-serum-albumin
#15
Reza Assaran Darban, Behzad Shareghi, Ahmad Asoodeh, Jamshidkhan Chamani
The present study was carried out to characterize ACE inhibitory peptides which are release from the trypsin hydrolysate of wheat gluten protein. The binding of two inhibitory peptide (P4 and P6) to human serum albumin (HSA) under physiological conditions has been investigated by multi- spectroscopic in combination with molecular modeling techniques. Time-resolved and quenching fluorescence spectroscopies results revealed that the quenching of HSA fluorescence by P4 and P6 in the binary and ternary systems caused HSA-peptides complexes formation...
November 29, 2016: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/27896938/population-pharmacokinetic-pharmacodynamic-modeling-of-tumor-size-dynamics-in-pembrolizumab-treated-advanced-melanoma
#16
M S Chatterjee, J Elassaiss-Schaap, A Lindauer, D C Turner, A Sostelly, T Freshwater, K Mayawala, M Ahamadi, J A Stone, R de Greef, A G Kondic, D P de Alwis
Pembrolizumab is a potent immune-modulating antibody active in advanced melanoma, as demonstrated in the KEYNOTE-001, -002, and -006 studies. Longitudinal tumor size modeling was pursued to quantify exposure-response relationships for efficacy. A mixture model was first developed based on an initial dataset from KEYNOTE-001 to describe four patterns of tumor growth and shrinkage. For subsequent analyses, tumor size measurements were adequately described by a single consolidated model structure that captured continuous tumor size with a combination of growth and regression terms, as well as a fraction of tumor responsive to therapy...
November 29, 2016: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/27896683/population-pharmacokinetics-of-an-extended-release-formulation-of-exenatide-following-single-and-multiple-dose-administration
#17
Brenda Cirincione, Jeffrey Edwards, Donald E Mager
Exenatide is a glucagon-like peptide-1 receptor agonist with both immediate- and extended-release (ER) formulations that are approved for the treatment of type 2 diabetes mellitus. Long-term exposure from the ER formulation is achieved through slow peptide release from a degradable microsphere formulation. The goal of this analysis was to develop a pharmacokinetic model for the ER formulation following single and once-weekly multiple-dose administration. Pharmacokinetic data were collected from two clinical trials-one that evaluated single-dose administration of 2...
November 28, 2016: AAPS Journal
https://www.readbyqxmd.com/read/27896568/how-can-a-good-idea-fail-basal-insulin-peglispro-ly2605541-for-the-treatment-of-type-2-diabetes
#18
REVIEW
Araceli Muñoz-Garach, María Molina-Vega, Francisco J Tinahones
INTRODUCTION: Lack of control in diabetic patients has stimulated the development of new insulin analogues. One of these was basal insulin peglispro (BIL) or LY2605541; it had a large hydrodynamic size, flat pharmacokinetic profile, half life of 2-3 days and acted preferably in the liver. METHODS: We reviewed the recent literature examining the pharmacokinetics, pharmacodynamics, efficacy and safety of BIL treatment in type 2 diabetes patients. RESULTS: The pharmacodynamic and pharmacokinetic outline of BIL seemed to have an advantage over neutral protamine Hagedorn and glargine insulins...
November 28, 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/27895517/influence-of-curcumin-on-the-pharmacodynamics-and-pharmacokinetics-of-gliclazide-in-animal-models
#19
Leela Krishna Vatsavai, Eswar Kumar Kilari
PURPOSE: Patients suffering from obesity-related diseases use multiple prescription drugs to control their condition, and it is therefore essential to determine the safety and efficacy of any combination. Gliclazide is one of the most commonly used drug of choice for treatment of type 2 diabetes, and curcumin is a widely used herbal supplement to counter obesity condition. The objective of this study was to investigate the effect of oral administration of curcumin on pharmacodynamics and pharmacokinetics of gliclazide in rats and rabbits to further evaluate the safety and effectiveness of this combination...
2016: Journal of Experimental Pharmacology
https://www.readbyqxmd.com/read/27895466/pharmacokinetics-pharmacodynamics-and-safety-of-ckd-519-a-cetp-inhibitor-in-healthy-subjects
#20
Choon Ok Kim, Eun Sil Oh, Chungam Choi, Yeonjoo Kim, Sera Lee, Semi Kim, Min Soo Park
CKD-519 is a selective and potent cholesteryl ester transfer protein (CETP) inhibitor being developed for the treatment of dyslipidemia to raise high-density lipoprotein cholesterol. We investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of CKD-519 in healthy adult subjects. A randomized, double-blinded, placebo-controlled, single ascending dose study was performed. Eight healthy subjects were enrolled in each CKD-519 dose group (25, 50, 100, 200, or 400 mg) and randomized to CKD-519 (n=6) or matching placebo (n=2)...
2016: Drug Design, Development and Therapy
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