Pharmacokinetics and target attainment of intravenous posaconazole in critically ill patients during extracorporeal membrane oxygenation

2021 ◽  
Author(s):  
Ruth Van Daele ◽  
Roger J Brüggemann ◽  
Erwin Dreesen ◽  
Pieter Depuydt ◽  
Bart Rijnders ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Fungal Infections ◽  
Rescue Therapy ◽  
Invasive Pulmonary Aspergillosis ◽  
Compartmental Analysis ◽  
Target Attainment ◽  
Membrane Oxygenation ◽  
Trough Concentrations

Abstract Background Posaconazole is an antifungal drug used for prophylaxis and treatment of invasive fungal infections. Severe influenza has been identified as a risk factor for invasive pulmonary aspergillosis in critically ill patients. In this population, extracorporeal membrane oxygenation (ECMO) is used as rescue therapy, although little is known about the pharmacokinetics (PK) of posaconazole during ECMO. Objectives To determine the PK and target attainment of six patients treated with IV posaconazole under ECMO and to develop a population PK model that can be used to simulate the PTA. Methods Critically ill patients treated with posaconazole and ECMO were included in this study. Plasma samples were collected at several timepoints within one dosing interval on two occasions: an early (Day 2–3) and a late (Day 4–7) sampling day. Daily trough concentrations were measured. Results The median (IQR) AUC0–24, CL and Vd were 34.3 (28.3–37.7) mg·h/L, 8.7 (8.0–10.6) L/h and 389 (314–740) L, if calculated with non-compartmental analysis based on the observed concentrations. All measured trough concentrations were ≥0.7 mg/L and 11/16 were ≥1 mg/L, which are the haematological thresholds for prophylaxis and treatment of invasive aspergillosis, respectively. The targeted PTA (>90%) was attained for prophylaxis but not for treatment. Conclusions ECMO does not appear to influence posaconazole exposure compared with haematology patients. However, some trough levels were below the lower limit for treatment. An a priori dose adjustment does not appear to be necessary but drug monitoring is recommended.

scholarly journals Meropenem Pharmacokinetics and Target Attainment in Critically Ill Patients Are Not Affected by Extracorporeal Membrane Oxygenation: A Matched Cohort Analysis

2021 ◽  
Vol 9 (6) ◽  
pp. 1310
Author(s):  
Matthias Gijsen ◽  
Erwin Dreesen ◽  
Pieter Annaert ◽  
Johan Nicolai ◽  
Yves Debaveye ◽  
...  
Keyword(s):  
Renal Function ◽  
Body Weight ◽  
Extracorporeal Membrane Oxygenation ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Matched Cohort ◽  
Target Attainment ◽  
Membrane Oxygenation ◽  
Population Pk ◽  
Dosing Intervals

Existing evidence is inconclusive whether meropenem dosing should be adjusted in patients receiving extracorporeal membrane oxygenation (ECMO). Therefore, the aim of this observational matched cohort study was to evaluate the effect of ECMO on pharmacokinetic (PK) variability and target attainment (TA) of meropenem. Patients admitted to the intensive care unit (ICU) simultaneously treated with meropenem and ECMO were eligible. Patients were matched 1:1, based on renal function and body weight, with non-ECMO ICU patients. Meropenem blood sampling was performed over one or two dosing intervals. Population PK modelling was performed using NONMEM7.5. TA was defined as free meropenem concentrations >2 or 8 mg/L (i.e., 1 or 4× minimal inhibitory concentration, respectively) throughout the whole dosing interval. In total, 25 patients were included, contributing 27 dosing intervals. The overall TA was 56% and 26% for the 2 mg/L and 8 mg/L target, respectively. Population PK modelling identified estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology equation and body weight, but not ECMO, as significant predictors. In conclusion, TA of meropenem was confirmed to be poor under standard dosing in critically ill patients but was not found to be influenced by ECMO. Future studies should focus on applying dose optimisation strategies for meropenem based on renal function, regardless of ECMO.

scholarly journals Predictors of insufficient peak amikacin concentration in critically ill patients on extracorporeal membrane oxygenation

Critical Care ◽  
2018 ◽  
Vol 22 (1) ◽  
Author(s):  
Cyril Touchard ◽  
Alexandra Aubry ◽  
Philippine Eloy ◽  
Nicolas Bréchot ◽  
Guillaume Lebreton ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Membrane Oxygenation

scholarly journals SP226AKI AND RRT ARE COMMON COMPLICATIONS IN CRITICALLY ILL PATIENTS REQUIRING VENO-ARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION

2017 ◽  
Vol 32 (suppl_3) ◽  
pp. iii180-iii180
Author(s):  
Georgios Vlachopanos ◽  
Jovana Kusic ◽  
Omar Shaikh ◽  
Nicholas Barrett ◽  
Marlies Ostermann
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Membrane Oxygenation

scholarly journals Model-Optimized Fluconazole Dose Selection for Critically Ill Patients Improves Early Pharmacodynamic Target Attainment without the Need for Therapeutic Drug Monitoring

2020 ◽  
Vol 65 (3) ◽  
Author(s):  
Indy Sandaradura ◽  
Jessica Wojciechowski ◽  
Deborah J. E. Marriott ◽  
Richard O. Day ◽  
Sophie Stocker ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Critically Ill ◽  
Drug Monitoring ◽  
Critically Ill Patients ◽  
Drug Exposure ◽  
Fungal Infections ◽  
Therapeutic Drug ◽  
Target Attainment ◽  
Dose Selection ◽  
Dose Individualization

ABSTRACT Fluconazole has been associated with higher mortality compared with the echinocandins in patients treated for invasive candida infections. Underexposure from current fluconazole dosing regimens may contribute to these worse outcomes, so alternative dosing strategies require study. The objective of this study was to evaluate fluconazole drug exposure in critically ill patients comparing a novel model-optimized dose selection method with established approaches over a standard 14-day (336-h) treatment course. Target attainment was evaluated in a representative population of 1,000 critically ill adult patients for (i) guideline dosing (800-mg loading and 400-mg maintenance dosing adjusted to renal function), (ii) guideline dosing followed by therapeutic drug monitoring (TDM)-guided dose adjustment, and (iii) model-optimized dose selection based on patient factors (without TDM). Assuming a MIC of 2 mg/liter, free fluconazole 24-h area under the curve (fAUC24) targets of ≥200 mg · h/liter and <800 mg · h/liter were used for assessment of target attainment. Guideline dosing resulted in underexposure in 21% of patients at 48 h and in 23% of patients at 336 h. The TDM-guided strategy did not influence 0- to 48-h target attainment due to inherent procedural delays but resulted in 37% of patients being underexposed at 336 h. Model-optimized dosing resulted in ≥98% of patients meeting efficacy targets throughout the treatment course, while resulting in less overexposure compared with guideline dosing (7% versus 14%) at 336 h. Model-optimized dose selection enables fluconazole dose individualization in critical illness from the outset of therapy and should enable reevaluation of the comparative effectiveness of this drug in patients with severe fungal infections.

Sign in / Sign up

Export Citation Format

Share Document