Population pharmacokinetics of micafungin over repeated doses in critically ill patients: a need for a loading dose?

2020 ◽  
Vol 72 (12) ◽  
pp. 1750-1760
Author(s):  
Iasonas Kapralos ◽  
Efstratios Mainas ◽  
Efthymios Neroutsos ◽  
Stella Apostolidi ◽  
Maria Siopi ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Loading Dose ◽  
Repeated Doses

scholarly journals Effect of Obesity on the Population Pharmacokinetics of Fluconazole in Critically Ill Patients

2016 ◽  
Vol 60 (11) ◽  
pp. 6550-6557 ◽  
Author(s):  
Abdulaziz S. Alobaid ◽  
Steven C. Wallis ◽  
Paul Jarrett ◽  
Therese Starr ◽  
Janine Stuart ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Maintenance Dose ◽  
Central Compartment ◽  
Pharmacokinetic Analysis ◽  
Morbidly Obese ◽  
Population Pharmacokinetic ◽  
Loading Dose ◽  
Intercompartmental Clearance

ABSTRACTOur objective was to describe the population pharmacokinetics of fluconazole in a cohort of critically ill nonobese, obese, and morbidly obese patients. Critically ill patients prescribed fluconazole were recruited into three body mass index (BMI) cohorts, nonobese (18.5 to 29.9 kg/m2), obese (30.0 to 39.9 kg/m2), and morbidly obese (≥40 kg/m2). Serial fluconazole concentrations were determined using a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were undertaken with Pmetrics. Twenty-one critically ill patients (11 male) were enrolled, including obese (n= 6) and morbidly obese (n= 4) patients. The patients mean ± standard deviation (SD) age, weight, and BMI were 54 ± 15 years, 90 ± 24 kg, and 31 ± 9 kg/m2, respectively. A two-compartment linear model described the data adequately. The mean ± SD population pharmacokinetic parameter estimates were clearance (CL) of 0.95 ± 0.48 liter/h, volume of distribution of the central compartment (Vc) of 15.10 ± 11.78 liter, intercompartmental clearance from the central to peripheral compartment of 5.41 ± 2.28 liter/h, and intercompartmental clearance from the peripheral to central compartment of 2.92 ± 4.95 liter/h. A fluconazole dose of 200 mg daily was insufficient to achieve an area under the concentration-time curve for the free, unbound drug fraction/MIC ratio of 100 for pathogens with MICs of ≥2 mg/liter in patients with BMI of >30 kg/m2. A fluconazole loading dose of 12 mg/kg and maintenance dose of 6 mg/kg/day achieved pharmacodynamic targets for higher MICs. A weight-based loading dose of 12 mg/kg followed by a daily maintenance dose of 6 mg/kg, according to renal function, is required in critically ill patients for pathogens with a MIC of 2 mg/liter.

scholarly journals Population Pharmacokinetics of Intravenous Polymyxin B in Critically Ill Patients: Implications for Selection of Dosage Regimens

2013 ◽  
Vol 57 (4) ◽  
pp. 524-531 ◽  
Author(s):  
Ana M. Sandri ◽  
Cornelia B. Landersdorfer ◽  
Jovan Jacob ◽  
Márcio M. Boniatti ◽  
Micheline G. Dalarosa ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Polymyxin B ◽  
Dosage Regimens ◽  
Selection Of

Corrigendum to “Population pharmacokinetics of continuous infusion of piperacillin in critically ill patients”. [Int J Antimicrob Agents 51 (2018) 594–600]

2019 ◽  
Vol 54 (3) ◽  
pp. 380
Author(s):  
Sofie A.M. Dhaese ◽  
Jason A. Roberts ◽  
Mieke Carlier ◽  
Alain G. Verstraete ◽  
Veronique Stove ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Population Pharmacokinetics ◽  
Critically Ill ◽  
Critically Ill Patients

scholarly journals Population pharmacokinetics and target attainment of ciprofloxacin in critically ill patients

2020 ◽  
Vol 76 (7) ◽  
pp. 957-967
Author(s):  
Alan Abdulla ◽  
Omar Rogouti ◽  
Nicole G. M. Hunfeld ◽  
Henrik Endeman ◽  
Annemieke Dijkstra ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Target Attainment

scholarly journals Population Pharmacokinetics of Piperacillin in Nonobese, Obese, and Morbidly Obese Critically Ill Patients

2017 ◽  
Vol 61 (3) ◽  
Author(s):  
Abdulaziz S. Alobaid ◽  
Steven C. Wallis ◽  
Paul Jarrett ◽  
Therese Starr ◽  
Janine Stuart ◽  
...  
Keyword(s):  
Critical Illness ◽  
Population Pharmacokinetics ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Central Compartment ◽  
Pharmacokinetic Analysis ◽  
Peripheral Compartment ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Intercompartmental Clearance

ABSTRACT The treatment of infections in critically ill obese and morbidly obese patients is challenging because of the combined physiological changes that result from obesity and critical illness. The aim of this study was to describe the population pharmacokinetics of piperacillin in a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients who received piperacillin-tazobactam were classified according to their body mass index (BMI) as nonobese, obese, and morbidly obese. Plasma samples were collected, and piperacillin concentrations were determined by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were performed using Pmetrics software. Thirty-seven critically ill patients (including 12 obese patients and 12 morbidly obese patients) were enrolled. The patients' mean ± standard deviation age, weight, and BMI were 50 ± 15 years, 104 ± 35 kg, and 38.0 ± 15.0 kg/m2, respectively. The concentration-time data were best described by a two-compartment linear model. The mean ± SD parameter estimates for the final covariate model were a clearance of 14.0 ± 7.1 liters/h, a volume of distribution of the central compartment of 49.0 ± 19.0 liters, an intercompartmental clearance from the central compartment to the peripheral compartment of 0.9 ± 0.6 liters · h−1, and an intercompartmental clearance from the peripheral compartment to the central compartment of 2.3 ± 2.8 liters · h−1. A higher measured creatinine clearance and shorter-duration infusions were associated with a lower likelihood of achieving therapeutic piperacillin exposures in patients in all BMI categories. Piperacillin pharmacokinetics are altered in the presence of obesity and critical illness. As with nonobese patients, prolonged infusions increase the likelihood of achieving therapeutic concentrations.

scholarly journals Tigecycline Therapy for Nosocomial Pneumonia due to Carbapenem-Resistant Gram-Negative Bacteria in Critically Ill Patients Who Received Inappropriate Initial Antibiotic Treatment: A Retrospective Case Study

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Xiaomai Wu ◽  
Yefei Zhu ◽  
Qiuying Chen ◽  
Liuyang Gong ◽  
Jian Lin ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Critically Ill ◽  
Nosocomial Pneumonia ◽  
Critically Ill Patients ◽  
Standard Dose ◽  
High Dose ◽  
Gram Negative Bacteria ◽  
Loading Dose ◽  
Icu Mortality ◽  
Carbapenem Resistant

Background. Nosocomial pneumonia due to carbapenem-resistant Gram-negative bacteria (CRGNB) is a growing concern because treatment options are limited and the mortality rate is high. The effect of tigecycline (TGC) on nosocomial pneumonia due to CRGNB in patients who have received inappropriate initial empiric antibiotic treatment (IIAT) is unclear. Therefore, this study aimed to examine the effect of TGC on nosocomial pneumonia due to CRGNB in critically ill patients who had received IIAT. Methods. A retrospective study was conducted in an adult respiratory intensive care unit. Data were obtained and analyzed for all patients who were treated with TGC ≥ 3 days for microbiologically confirmed nosocomial pneumonia due to CRGNB and had experienced initial antibiotic failure. Clinical and microbiological outcomes were investigated. Results. Thirty-one patients with hospital-acquired pneumonia or ventilator-associated pneumonia were included in the study. The majority of the responsible organisms were carbapenem-resistant Acinetobacter baumannii (67.7%), followed by Klebsiella pneumoniae (16.1%) and Escherichia coli (9.7%). Twenty patients were treated with high-dose TGC therapy (100 mg every 12 h after a 200 mg loading dose), and the others received a standard-dose therapy (50 mg every 12 h after a 100 mg loading dose). The duration of TGC therapy was 14.3±2.8 days. The global clinical cure rate and the microbiological eradication rate were 48.4% and 61.3%, respectively. The overall ICU mortality rate was 45.2%. A higher score on the Acute Physiology and Chronic Health Evaluation II and a longer duration of IIAT were associated with clinical failure. High-dose TGC therapy had a higher clinical success rate [65.0% (13/20) versus 18.2% (2/11), P=0.023] and a lower ICU mortality rate [30.0% (6/20) versus 72.7% (8/11), P=0.031] than the standard-dose therapy. Conclusions. TGC, especially a high-dose regimen, might be a justifiable option for critically ill patients with nosocomial pneumonia due to CRGNB who have received IIAT when the options for these patients are limited.

scholarly journals Population Pharmacokinetics of Dexmedetomidine in Critically Ill Patients

2013 ◽  
Vol 33 (8) ◽  
pp. 579-587 ◽  
Author(s):  
Pyry Antti Välitalo ◽  
Tuula Ahtola-Sätilä ◽  
Andrew Wighton ◽  
Toni Sarapohja ◽  
Pasi Pohjanjousi ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Critically Ill ◽  
Critically Ill Patients
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