A5053818345- Antibiotics Pharmacokinetics and Efficacy
- Antibiotic Resistance in Bacteria
- Pneumonia and Respiratory Infections
- Platelet Disorders and Treatments
- Antiplatelet Therapy and Cardiovascular Diseases
- Anesthesia and Sedative Agents
- Antibiotic Use and Resistance
- Epilepsy research and treatment
- Pharmaceutical studies and practices
- Heparin-Induced Thrombocytopenia and Thrombosis
- Drug Transport and Resistance Mechanisms
- Cystic Fibrosis Research Advances
- Pharmacogenetics and Drug Metabolism
- Statistical Methods in Clinical Trials
- Urinary Tract Infections Management
- Drug-Induced Hepatotoxicity and Protection
- Protein Interaction Studies and Fluorescence Analysis
- Venous Thromboembolism Diagnosis and Management
- Antimicrobial Resistance in Staphylococcus
- SARS-CoV-2 and COVID-19 Research
- Lipid metabolism and disorders
- COVID-19 Clinical Research Studies
- Renal Diseases and Glomerulopathies
- Biosimilars and Bioanalytical Methods
- Complement system in diseases
Shionogi (Japan)
2014-2025
Futaba (Japan)
2005-2024
Hiroshima University
2002-2009
Cefiderocol is a novel parenteral siderophore cephalosporin that shows potent efficacy against various Gram-negative bacteria, including carbapenem-resistant strains, in vitro and preclinical models of infection. The aim the present study was to evaluate pharmacokinetics (PK), safety, tolerability cefiderocol after both single multiple dosing by intravenous infusion over 60 min healthy adult subjects. A single-ascending-dose at doses 100, 250, 500, 1,000, 2,000 mg conducted 40 Japanese males...
Background & AimsPlatelet transfusion is used to prevent hemorrhagic events in patients with thrombocytopenia undergoing invasive procedures, but there are many disadvantages. We evaluated the efficacy and safety of lusutrombopag chronic liver disease procedures.MethodsWe performed a double-blind, parallel-group, phase 3 study 96 (platelet counts below 50,000/μL) procedures from October 2013 May 2014 at 81 centers Japan. Patients were randomly assigned (1:1) groups given once-daily (3 mg) or...
Abstract Cefiderocol, a new injectable siderophore cephalosporin antibiotic, has promising in vitro and vivo activity against Gram‐negative bacteria including multidrug‐resistant Pseudomonas aeruginosa, Acinetobacter baumannii , Klebsiella pneumoniae . Cefiderocol is mainly renally eliminated. The pharmacokinetics safety of cefiderocol subjects with renal impairment were assessed following single 1000‐mg intravenous 1‐hour infusion cefiderocol. Subjects mild, moderate, or severe end‐stage...
ABSTRACT Cefiderocol, a novel parenteral siderophore cephalosporin, exhibits potent efficacy against most Gram-negative bacteria, including carbapenem-resistant strains. Since cefiderocol is excreted primarily via the kidneys, this study was conducted to develop population pharmacokinetics (PK) model determine dose adjustment based on renal function. Population PK models were developed data for concentrations in plasma, urine, and dialysate with nonlinear mixed-effects approach. Monte-Carlo...
Thrombocytopenia represents an obstacle for invasive procedures in chronic liver disease (CLD) patients. We aimed to estimate the appropriate dose and evaluate efficacy safety of lusutrombopag treatment thrombocytopenia before percutaneous radiofrequency ablation (RFA) primary hepatic cancer patients with CLD.In this multicenter, randomized, double-blind, placebo-controlled study conducted Japan, 61 CLD platelet count < 50 × 103/µL at screening were randomized placebo or 2, 3, 4 mg once...
Cefiderocol is a novel siderophore cephalosporin with antibacterial activity against Gram-negative bacteria, including carbapenem-resistant strains. The standard dosing regimen of cefiderocol 2 g administered every 8 hours over 3 infusion in patients creatinine clearance (CrCL) 60 to 119 ml/min, and it adjusted for <60 ml/min or ≥120 CrCL. A population pharmacokinetic (PK) model was constructed using 3,427 plasma concentrations from 91 uninfected subjects 425 infected pneumonia, bloodstream...
Cefiderocol, a novel siderophore cephalosporin, has shown potent activity against Gram-negative bacteria, including MDR pathogens. Cefiderocol is under clinical investigation for the treatment of serious infections nosocomial pneumonia.This study assessed intrapulmonary penetration after single intravenous dose cefiderocol (2000 mg infused over 60 min) in healthy adult males.Each subject underwent one bronchoscopy with bronchoalveolar lavage (BAL) to collect BAL fluid (BALF). Fifteen...
Lung penetration of cefiderocol, a novel siderophore cephalosporin approved for treatment nosocomial pneumonia, has previously been evaluated in healthy subjects. This study assessed the intrapulmonary pharmacokinetic profile cefiderocol at steady state hospitalized, mechanically ventilated pneumonia patients.Patients received 2 g (or ≤1.5 if renally impaired), administered IV q8h as 3 h infusion, or q6h patients had augmented renal function (estimated CLCR > 120 mL/min). After multiple...
ABSTRACT Cefiderocol, a novel parenteral siderophore cephalosporin, exhibits potent efficacy against most Gram-negative bacteria, including carbapenem-resistant strains. The aim of this study was to perform population pharmacokinetic (PK) analysis based on plasma cefiderocol concentrations in healthy subjects, subjects with various degrees renal function, and patients complicated urinary tract infection (cUTI) or acute uncomplicated pyelonephritis (AUP) caused by pathogens calculate the...
The need for continuous renal replacement therapy (CRRT) in critically ill patients with serious infections is associated clinical failure, emergence of resistance, and excess mortality. These poor outcomes are attributable large part to subtherapeutic antimicrobial exposure failure achieve target pharmacokinetic/pharmacodynamic (PK/PD) thresholds during CRRT. Cefiderocol a novel siderophore cephalosporin broad vitro activity against resistant pathogens often used treat patients, including...
The objectives of this study were to characterize the concentration-time profiles total radioactivity equivalent and unchanged cefiderocol, route(s) elimination mass balance, safety cefiderocol after intravenous administration a single 1000-mg (100 μCi) dose [14 C]-cefiderocol as 1-hour infusion in healthy adult male subjects. Unchanged accounted for majority plasma, partitioning into red blood cells was negligible. recovery complete all subjects within 120 hours initiation (101.5%...
We aim to evaluate the safety and pharmacokinetic (PK) properties of cefiderocol in Chinese participants, following single subsequent multiple administrations 2 g q8h with 3-h intravenous infusion, predict its efficacy for treatment Gram-negative bacilli (GNB) infection based on PK/pharmacodynamic (PD) analysis. This was an open-label, single-center, single- multiple-dose phase I study, conducted from September 2022 October 2022, 12 eligible healthy adults (6 men 6 women). The PK profiles...
Cefiderocol is a siderophore cephalosporin for the treatment of infections caused by gram-negative bacteria including carbapenem-resistant strains. The aim this study was to develop an intrapulmonary pharmacokinetic (PK) model cefiderocol and assess PK profile in lungs. An developed using concentration data plasma epithelial lining fluid (ELF) from 7 patients with pneumonia requiring mechanical ventilation 20 healthy subjects. Subsequently, applied ELF exposure 125 nosocomial pneumonia....
PurposeCefiderocol is a novel siderophore cephalosporin with potent activity against gram-negative bacteria, including multidrug-resistant strains. This Phase I study was conducted to assess the tolerability of single-ascending doses cefiderocol (part 1) and effect on cardiac repolarization, assessed using electrocardiographic corrected QT interval (QTcF) other ECG parameters 2), in healthy adult subjects.MethodsPart 1 randomized, double-blind, placebo-controlled, dose male female subjects....
Background: Multidrug-resistant Gram-negative bacterial infections are increasing globally in neonates, infants and children; antibiotic options limited. Methods: This international, multicenter, open-label phase 2 study, investigated the pharmacokinetics, safety tolerability of single-dose multiple-dose cefiderocol [as a 3-hour infusion (every 8 hours) dosed at 2000 mg for body weight ≥34 kg 60 mg/kg <34 kg], over range renal function, hospitalized pediatric patients with aerobic...
Ensitrelvir, a novel oral inhibitor of 3C-like protease SARS-CoV-2, shows efficacy and safety in participants with mild to moderate COVID-19. Since urinary recovery ensitrelvir ranged from 12.9% 21.8% across dose groups given 20–1000 mg single-ascending study, renal excretion contributes the elimination ensitrelvir. Therefore, effect impairment on pharmacokinetics needed be evaluated. This study (NCT05363215) was phase 1, open-label, nonrandomized, parallel-group study. The function...
Abstract When planning pediatric clinical trials, optimizing the sample size of neonates/infants is essential because it difficult to enroll these subjects. In this simulation study, we evaluated using a model‐based optimal approach for identifying their pharmacokinetics cefiderocol. We assessed usefulness data estimation performance (accuracy and variance parameter estimation) from adults impact very young subjects, including preterm neonates. Stochastic were utilized assess allocation age...