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Therapeutic drug monitoring

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https://www.readbyqxmd.com/read/29332645/plasma-levels-of-rifampicin-and-pyrazinamide-with-pre-and-post-meal-administration-in-tuberculosis-patients
#1
Parveen Kumar Sharma, Rekha Bansal, Ashok Kumar Bhardwaj, Vivek Sood, Atal Sood, Yogendra Padwad
CONTEXT: Various factors affect plasma concentrations of antitubercular drugs in different populations so dosing schedule should be adjusted after therapeutic drug monitoring. AIMS: To study variability in plasma concentrations of Rifampicin and Pyrazinamide with pre and post-meal administration of drugs in tuberculosis patients. METHODS AND MATERIAL: 52 patients of pulmonary tuberculosis, divided in to two groups, pre and post-meal through systemic randomization...
January 2018: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/29330783/clinical-pharmacokinetics-and-pharmacodynamics-of-infliximab-in-the-treatment-of-inflammatory-bowel-disease
#2
REVIEW
Amy Hemperly, Niels Vande Casteele
Infliximab was the first monoclonal antibody to be approved for the treatment of pediatric and adult patients with moderately to severely active Crohn's disease (CD) and ulcerative colitis (UC). It has been shown to induce and maintain both clinical remission and mucosal healing in pediatric and adult patients with inflammatory bowel disease (IBD) who are unresponsive or refractory to conventional therapies. The administration of infliximab is weight-based and the drug is administered intravenously. The volume of distribution of infliximab is low and at steady state ranges from 4...
January 12, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29330466/target-engagement-imaging-of-parp-inhibitors-in-small-cell-lung-cancer
#3
Brandon Carney, Susanne Kossatz, Benjamin H Lok, Valentina Schneeberger, Kishore K Gangangari, Naga Vara Kishore Pillarsetty, Wolfgang A Weber, Charles M Rudin, John T Poirier, Thomas Reiner
Insufficient chemotherapy response and rapid disease progression remain concerns for small-cell lung cancer (SCLC). Oncologists rely on serial CT scanning to guide treatment decisions, but this cannot assess in vivo target engagement of therapeutic agents. Biomarker assessments in biopsy material do not assess contemporaneous target expression, intratumoral drug exposure, or drug-target engagement. Here, we report the use of PARP1/2-targeted imaging to measure target engagement of PARP inhibitors in vivo. Using a panel of clinical PARP inhibitors, we show that PARP imaging can quantify target engagement of chemically diverse small molecule inhibitors in vitro and in vivo...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29328863/overexpression-of-mtor-and-p-240-244-s6-in-idh1-wild-type-human-glioblastomas-is-predictive-of-low-survival
#4
Luis Eduardo Machado, Arthur William Alvarenga, Fernanda Ferreira da Silva, Martín Roffé, Maria Dirlei Begnami, Luís Fernando Bleggi Torres, Isabela Werneck da Cunha, Vilma Regina Martins, Glaucia Noeli Maroso Hajj
PI3K/Akt/mTOR pathway activation is a hallmark of high-grade gliomas, which prompted clinical trials for the use of PI3K and mTOR inhibitors. However, the poor results in the original trials suggested that better patient profiling was needed for such drugs. Thus, accurate and reproducible monitoring of mTOR complexes can lead to improved therapeutic strategies. In this work, we evaluated the expression and phosphorylation of mTOR, RAPTOR, and rpS6 in 195 human astrocytomas and 30 normal brain tissue samples...
January 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/29327084/bace1-inhibition-more-effectively-suppresses-initiation-than-progression-of-%C3%AE-amyloid-pathology
#5
Finn Peters, Hazal Salihoglu, Eva Rodrigues, Etienne Herzog, Tanja Blume, Severin Filser, Mario Dorostkar, Derya R Shimshek, Nils Brose, Ulf Neumann, Jochen Herms
BACE1 is the rate-limiting protease in the production of synaptotoxic β-amyloid (Aβ) species and hence one of the prime drug targets for potential therapy of Alzheimer's disease (AD). However, so far pharmacological BACE1 inhibition failed to rescue the cognitive decline in mild-to-moderate AD patients, which indicates that treatment at the symptomatic stage might be too late. In the current study, chronic in vivo two-photon microscopy was performed in a transgenic AD model to monitor the impact of pharmacological BACE1 inhibition on early β-amyloid pathology...
January 11, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29325448/impact-of-cyp2c19-genotype-on-escitalopram-exposure-and-therapeutic-failure-a-retrospective-study-based-on-2-087-patients
#6
Marin M Jukić, Tore Haslemo, Espen Molden, Magnus Ingelman-Sundberg
OBJECTIVE: The antidepressant escitalopram is predominantly metabolized by the polymorphic CYP2C19 enzyme. The authors investigated the effect of CYP2C19 genotype on exposure and therapeutic failure of escitalopram in a large patient population. METHOD: A total of 4,228 escitalopram serum concentration measurements from 2,087 CYP2C19-genotyped patients 10-30 hours after drug intake were collected retrospectively from the drug monitoring database at Diakonhjemmet Hospital in Oslo...
January 12, 2018: American Journal of Psychiatry
https://www.readbyqxmd.com/read/29324625/comparison-of-the-ark-immunoassay-with-high-performance-liquid-chromatography-with-ultraviolet-detection-for-therapeutic-drug-monitoring-of-linezolid
#7
Simone Castoldi, Valeria Cozzi, Sara Baldelli, Serena Fucile, Emilio Clementi, Dario Cattaneo
BACKGROUND: An enzymatic immunoassay is under development by ARK Diagnostics, Inc for the quantification of plasma concentrations of linezolid (LZD). In this study, the authors aimed to assess the performance of this immunoassay using a validated high-performance liquid chromatography (HPLC) ultraviolet method as reference. METHODS: Within- and between-day in vitro inaccuracy and imprecision of the ARK LZD assay were firstly tested using spiked quality controls (QC) provided by the kit manufacturer...
February 2018: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29321022/serum-metabolic-profiling-identified-a-distinct-metabolic-signature-in-patients-with-idiopathic-pulmonary-fibrosis-a-potential-biomarker-role-for-lysopc
#8
Barbara Rindlisbacher, Cornelia Schmid, Thomas Geiser, Cédric Bovet, Manuela Funke-Chambour
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology. Patients present loss of lung function, dyspnea and dry cough. Diagnosis requires compatible radiologic imaging and, in undetermined cases, invasive procedures such as bronchoscopy and surgical lung biopsy. The pathophysiological mechanisms of IPF are not completely understood. Lung injury with abnormal alveolar epithelial repair is thought to be a major cause for activation of profibrotic pathways in IPF...
January 10, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29319495/investigation-of-the-age-dependency-of-vancomycin-clearance-by-population-pharmacokinetic-modeling
#9
Muhammad Usman, Manfred Fobker, Georg Hempel
PURPOSE: The aim of this study was to evaluate the influence of age and other possible covariates on vancomycin clearance in order to define a possible cut off value of age for dose optimization in elderly patients from data obtained during therapeutic drug monitoring. MATERIALS AND METHODS: Population pharmacokinetic analysis of 256 samples obtained from 144 patients was performed by using NONMEM®. A one-compartment model was applied as the base model with first-order conditional estimation method with interaction (FOCE-I)...
January 10, 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29319234/comparative-pharmacokinetics-of-trandolapril-its-active-metabolite-and-verapamil-in-human-plasma-of-egyptian-population-using-hplc-ms-ms
#10
Ragaa Magdy, Ahmed H El-Khatib, Ahmed Hemdan, Omar Abd Elaziz, Maha Farouk, Michael W Linscheid
Trandolapril and verapamil are commonly used antihypertensive drugs. However, there is a lack of available data on the change of their pharmacokinetics in patients with liver or kidney impairment and hence the need for dose adjustment. In the presented work, a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated for the monitoring of trandolapril, its active metabolite trandolaprilat, and verapamil in human plasma of patients with renal impairment and/or liver insufficiency...
January 10, 2018: Drug Testing and Analysis
https://www.readbyqxmd.com/read/29318099/a-small-molecule-impedes-insulin-fibrillation-another-new-role-of-phenothiazine-derivatives
#11
Meghomukta Mukherjee, Jagannath Jana, Subhrangsu Chatterjee
Protein misfolding is interrelated to several diseases, including neurodegenerative diseases and type II diabetes. Misfolded/unfolded proteins produce soluble oligomers that accumulate into "amyloid plaques". Inhibition of amyloid-plaque formation by those misfolded/unfolded proteins will lead to the invention of new therapeutic approaches for amyloid-related diseases. Herein, methylene blue (MB), a well-defined drug against multiple diseases and disorders, is used to impede insulin fibrillation. In this study, we perform an array of in vitro experiments to monitor the effects of MB on the fibrillation of bovine insulin...
January 2018: ChemistryOpen
https://www.readbyqxmd.com/read/29317432/in-silico-evaluation-of-pharmacokinetic-optimization-for-antimitogram-based-clinical-trials
#12
Skerdi Haviari, Benoît You, Michel Tod
Antimitograms are prototype in vitro tests for evaluating chemotherapeutic efficacy using patient-derived primary cancer cells. These tests might help optimize treatment from a pharmacodynamic (PD) standpoint by guiding treatment selection. However, they are technically challenging and require refinements and trials to demonstrate benefit in order to be widely used. In this study, we performed simulations aimed at exploring how to validate antimitograms and how to complement them by pharmacokinetic (PK) optimization...
January 9, 2018: Cancer Research
https://www.readbyqxmd.com/read/29317275/increasing-infliximab-dose-based-on-symptoms-biomarkers-and-serum-drug-concentrations-does-not-increase-clinical-endoscopic-or-corticosteroid-free-remission-in-patients-with-active-luminal-crohn-s-disease
#13
Geert D'Haens, Severine Vermeire, Guy Lambrecht, Filip Baert, Peter Bossuyt, Benjamin Pariente, Anthony Buisson, Yoram Bouhnik, Jérôme Filippi, Janneke Vander Woude, Philippe Van Hootegem, Jacques Moreau, Edouard Louis, Denis Franchimont, Martine De Vos, Fazia Mana, Laurent Peyrin-Biroulet, Hedia Brixi, Matthieu Allez, Philip Caenepeel, Alexandre Aubourg, Bas Oldenburg, Marieke Pierik, Ann Gils, Sylvie Chevret, David Laharie
BACKGROUND & AIMS: A combination of infliximab and immunomodulators is the most efficacious treatment for Crohn's disease (CD). Patients have the best outcomes when their serum concentrations of these drugs are above a determined therapeutic threshold. We performed a prospective, randomized trial to determine whether therapeutic drug monitoring (TDM) to maintain serum levels of infliximab above 3 μg/mL produced higher rates of clinical and endoscopic remission than adapting dose based only on symptoms...
January 6, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29317184/alternative-approaches-to-the-therapeutic-drug-monitoring-of-prophylactic-posaconazole-in-haematology-patients
#14
T-A Vyzantiadis, E Yannaki, D A Oliver, A-M Markantonatou, Z Boussiou, A Louka, E Zachrou, E M Johnson
OBJECTIVE: The intention of the study was to assess whether a unique daily specimen is adequate for prophylactic posaconazole TDM in haematology patients and if bioassay and HPLC produce similar results and could be equally used in clinical setting. METHOD: Serum specimens from thirty haematology patients were collected at the end of the first and second week of treatment, just before the morning dose, 2 and 6 to 8hours afterwards. Levels were measured by bioassay in 157 specimens and additionally by HPLC in 51 of them...
January 6, 2018: Journal de Mycologie Médicale
https://www.readbyqxmd.com/read/29316372/can-therapeutic-drug-monitoring-increase-the-safety-of-imatinib-in-gist-patients
#15
Wei Zhuang, Jing-Dun Xie, Shan Zhou, Zhi-Wei Zhou, Yi Zhou, Xiao-Wei Sun, Xiu-Hong Yuan, Min Huang, Si Liu, Shuang Xin, Qi-Biao Su, Hai-Bo Qiu, Xue-Ding Wang
Imatinib at 400 mg daily is the standard treatment for patients affected with CML and GIST. The intervariability in plasma concentration is very significant. In many reports, a good therapeutic effect is attributed to an adequate concentration of Imatinib. However, few studies have been conducted to investigate the association between plasma concentration and side effects. Besides, no upper concentration limit of Imatinib plasma concentration detection has been established. The correlation of Imatinib trough concentrations (Cmin ) with adverse effects (AEs) was described here...
January 7, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29315954/development-and-validation-of-an-assay-to-analyze-atazanavir-in-human-hair-via-liquid-chromatography-tandem-mass-spectrometry-lc-ms-ms
#16
Nhi Phung, Karen Kuncze, Hideaki Okochi, Alexander Louie, Leslie Z Benet, Igho Ofokotun, David W Haas, Judith S Currier, Tariro D Chawana, Anandi N Sheth, Peter Bacchetti, Monica Gandhi, Howard Horng
Assays to quantify antiretrovirals in hair samples are increasingly used to monitor adherence and exposure in both HIV prevention and treatment studies. Atazanavir (ATV) is a protease inhibitor used in combination antiretroviral therapy (ART). We developed and validated a liquid chromatography tandem mass spectrometry (LC-MS/MS)-based method to quantify ATV in human hair, per the NIH Division of AIDS' Clinical Pharmacology Quality Assurance (CPQA) program and the FDA bioanalytical method validation guidelines...
January 9, 2018: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/29315506/optimization-of-voriconazole-therapy-for-the-treatment-of-invasive-fungal-infections-in-adults
#17
Naveen Mangal, Issam Hamadeh, Meghan J Arwood, Larisa H Cavallari, Tanay S Samant, Kenneth P Klinker, Jurgen Bulitta, Stephan Schmidt
Therapeutic concentrations of voriconazole in invasive fungal infections (IFIs) are ensured using drug monitoring approach, which relies on attainment of steady state pharmacokinetics. For voriconazole, time to reach steady state can vary from 5-7 days, not optimal for critically ill patients. We developed a population pharmacokinetic/pharmacodynamic model-based approach to predict doses which can maximize the net benefit (probability of efficacy - probability of adverse events) and ensure therapeutic concentrations, early on during treatment...
January 9, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29314123/editorial-early-post-induction-anti-tnf-drug-monitoring-can-predict-long-term-therapeutic-outcomes-in-inflammatory-bowel-disease
#18
EDITORIAL
K Papamichael, A S Cheifetz
No abstract text is available yet for this article.
February 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29314090/development-and-validation-of-lc-ms-ms-method-for-simultaneous-determination-of-sofosbuvir-and-daclatasvir-in-human-plasma-application-to-pharmacokinetic-study
#19
Ola M Abdallah, Ahmed M Abdel-Megied, Amira S Gouda
The first simple and highly sensitive Liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical method was developed and fully validated for the simultaneous determination of newly discovered antiviral drugs namely, Sofosbuvir (SOF) and Daclatasvir (DAC) in human plasma. Tadalafil (TAD) was used as internal standard (IS). SOF, DAC and TAD (IS) were extracted from plasma using liquid-liquid extraction technique with methyl tert-butyl ether. The chromatographic separation was carried out using ZorbaxSB-C18 column (4...
January 3, 2018: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29313577/a-randomized-controlled-phase-iii-clinical-trial-to-evaluate-the-efficacy-and-tolerability-of-risorine-with-conventional-rifampicin-in-the-treatment-of-newly-diagnosed-pulmonary-tuberculosis-patients
#20
Naresh Patel, K Jagannath, Agam Vora, Mukesh Patel, Anand Patel
Background: The overall goals for treatment of Tuberculosis (TB) are to cure individual patient and to minimize the transmission of Mycobacterium tuberculosis. At the time of study conduction, the standard treatment for newly diagnosed tuberculosis patients consisted of an intensive phase for two months with four drugs (HRZE), followed by continuation phase for four months with two drugs (HR). Rifampicin, which is very effective against Mycobacterium tuberculosis, in both the phases of treatment, has certain concerns, which includes, decreased bioavailability with chronic use and hepatotoxicity...
September 2017: Journal of the Association of Physicians of India
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