keyword
https://read.qxmd.com/read/35598857/translational-in-vitro-and-in-vivo-pkpd-modelling-for-apramycin-against-gram-negative-lung-pathogens-to-facilitate-prediction-of-human-efficacious-dose-in-pneumonia
#1
JOURNAL ARTICLE
Vincent Aranzana-Climent, Diarmaid Hughes, Sha Cao, Magdalena Tomczak, Malgorzata Urbas, Dorota Zabicka, Carina Vingsbo Lundberg, Jon Hansen, Johan Lindberg, Sven N Hobbie, Lena E Friberg
OBJECTIVES: New drugs and methods to efficiently fight carbapenem-resistant gram-negative pathogens are sorely needed. In this study, we characterized the preclinical pharmacokinetics (PK) and pharmacodynamics of the clinical stage drug candidate apramycin in time kill and mouse lung infection models. Based on in vitro and in vivo data, we developed a mathematical model to predict human efficacy. METHODS: Three pneumonia-inducing gram-negative species Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae were studied...
May 20, 2022: Clinical Microbiology and Infection
https://read.qxmd.com/read/34452260/model-informed-repurposing-of-medicines-for-sars-cov-2-extrapolation-of-antiviral-activity-and-dose-rationale-for-paediatric-patients
#2
JOURNAL ARTICLE
Federico Romano, Salvatore D'Agate, Oscar Della Della Pasqua
Repurposing of remdesivir and other drugs with potential antiviral activity has been the basis of numerous clinical trials aimed at SARS-CoV-2 infection in adults. However, expeditiously designed trials without careful consideration of dose rationale have often resulted in treatment failure and toxicity in the target patient population, which includes not only adults but also children. Here we show how paediatric regimens can be identified using pharmacokinetic-pharmacodynamic (PKPD) principles to establish the target exposure and evaluate the implications of dose selection for early and late intervention ...
August 19, 2021: Pharmaceutics
https://read.qxmd.com/read/33316399/efficacy-of-ebl-1003-apramycin-against-acinetobacter-baumannii-lung-infections-in-mice
#3
JOURNAL ARTICLE
Katja Becker, Vincent Aranzana-Climent, Sha Cao, Anna Nilsson, Reza Shariatgorji, Klara Haldimann, Björn Platzack, Diarmaid Hughes, Per E Andrén, Erik C Böttger, Lena E Friberg, Sven N Hobbie
OBJECTIVES: Novel therapeutics are urgently required for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) causing critical infections with high mortality. Here we assessed the therapeutic potential of the clinical-stage drug candidate EBL-1003 (crystalline free base of apramycin) in the treatment of CRAB lung infections. METHODS: The genotypic and phenotypic susceptibility of CRAB clinical isolates to aminoglycosides and colistin was assessed by database mining and broth microdilution...
December 11, 2020: Clinical Microbiology and Infection
https://read.qxmd.com/read/31951139/model-informed-drug-development-in-pulmonary-delivery-semimechanistic-pharmacokinetic-pharmacodynamic-modeling-for-evaluation-of-treatments-against-chronic-pseudomonas-aeruginosa-lung-infections
#4
JOURNAL ARTICLE
Tomás Sou, Irena Kukavica-Ibrulj, Roger C Levesque, Lena E Friberg, Christel A S Bergström
Antibiotic resistance is a major public health threat worldwide, and among others, about 80% of cystic fibrosis patients have chronic Pseudomonas aeruginosa (PA) lung infection resistant to many current antibiotics. Novel treatment strategies are therefore urgently needed. For lung infections, direct delivery of treatments to the site of action in the airway can achieve a higher local concentration with minimal systemic exposure and hence avoid risks of unwanted systemic adverse effects. Previously, a rat preclinical disease model for PA chronic lung infections has been reported...
April 6, 2020: Molecular Pharmaceutics
https://read.qxmd.com/read/27578330/a-whole-body-physiologically-based-pharmacokinetic-wb-pbpk-model-of-ciprofloxacin-a-step-towards-predicting-bacterial-killing-at-sites-of-infection
#5
JOURNAL ARTICLE
Muhammad W Sadiq, Elisabet I Nielsen, Dalia Khachman, Jean-Marie Conil, Bernard Georges, Georges Houin, Celine M Laffont, Mats O Karlsson, Lena E Friberg
The purpose of this study was to develop a whole-body physiologically based pharmacokinetic (WB-PBPK) model for ciprofloxacin for ICU patients, based on only plasma concentration data. In a next step, tissue and organ concentration time profiles in patients were predicted using the developed model. The WB-PBPK model was built using a non-linear mixed effects approach based on data from 102 adult intensive care unit patients. Tissue to plasma distribution coefficients (Kp) were available from the literature and used as informative priors...
April 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://read.qxmd.com/read/20439610/intrapulmonary-pharmacokinetics-and-pharmacodynamics-of-micafungin-in-adult-lung-transplant-patients
#6
JOURNAL ARTICLE
Thomas J Walsh, Sylvain Goutelle, Roger W Jelliffe, Jeffrey A Golden, Emily A Little, Catherine DeVoe, Diana Mickiene, Maggie Hayes, John E Conte
Invasive pulmonary aspergillosis is a life-threatening infection in lung transplant recipients; however, no studies of the pharmacokinetics and pharmacodynamics (PKPD) of echinocandins in transplanted lungs have been reported. We conducted a single-dose prospective study of the intrapulmonary and plasma PKPD of 150 mg of micafungin administered intravenously in 20 adult lung transplant recipients. Epithelial lining fluid (ELF) and alveolar cell (AC) samples were obtained via bronchoalveolar lavage performed 3, 5, 8, 18, or 24 h after initiation of infusion...
August 2010: Antimicrobial Agents and Chemotherapy
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