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Pharmacokinetics of Isavuconazole During Extracorporeal Membrane Oxygenation Support in Critically Ill Patients: A
Laura Doménech-Moral1, Sonia García-García1, Alba Pau-Parra1
1Pharmacy Department, Vall d'Hebron University Hospital, Basic, Translational and Clinical Pharmacy Research Group, Vall d'Hebron Research Institute, 08035 Barcelona, Spain.
Background/Objectives:
Extracorporeal membrane oxygenation (ECMO) is increasingly used in critically ill patients, but may significantly alter the pharmacokinetics (PK) of antifungals. Data on plasma concentrations of Isavuconazole (IsaPlasm) in ECMO patients are limited. Our objective is to evaluate Isavuconazole exposure and variability in critically ill COVID-19 patients receiving ECMO.
Methods:
We conducted a pharmacokinetic analysis of Isavuconazole in critically ill patients receiving Veno-Venous ECMO for respiratory support. Plasma concentrations were measured using therapeutic drug monitoring (TDM) at multiple time points, including sampling before and after the membrane oxygenator. PK parameters-Area Under Curve (AUC0-24), Minimum Plasma Concentration (Cmin), Elimination Half-Life (T1/2), volume of distribution (Vd), and clearance (CL)-were estimated and compared with published data in non-ECMO populations.
Results:
Five patients were included. The median AUC0-24 was 227.3 µg·h/mL (IQR 182.4-311.35), higher than reported in non-ECMO patients. The median Vd was 761 L (727-832), suggesting extensive peripheral distribution and potential drug sequestration in the ECMO circuit. CL was increased (1.6 L/h, IQR 1.5-3.4). Two patients with recently replaced ECMO circuits exhibited significant drug loss across the membrane. Obesity and hypoalbuminemia were identified as factors associated with altered drug exposure.
Conclusions:
Isavuconazole pharmacokinetics show marked variability in critically ill ECMO patients. Increased AUC and Vd, along with reduced clearance, highlight the need for individualized dosing.
Insights
Extracorporeal membrane oxygenation (ECMO) significantly alters Isavuconazole pharmacokinetics in critically ill patients. Individualized dosing is crucial due to increased drug exposure and variability observed in ECMO patients.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Critical Care Medicine
- Infectious Diseases
Background:
- Extracorporeal membrane oxygenation (ECMO) use is rising in critical care.
- ECMO can alter antifungal drug pharmacokinetics (PK).
- Limited data exist on Isavuconazole PK in ECMO patients.
Purpose of the Study:
- Evaluate Isavuconazole exposure and variability.
- Focus on critically ill COVID-19 patients on ECMO.
- Inform dosing strategies for this population.
Main Methods:
- Pharmacokinetic analysis of Isavuconazole.
- Therapeutic drug monitoring (TDM) in Veno-Venous ECMO patients.
- Estimation and comparison of PK parameters (AUC, Cmin, T1/2, Vd, CL).
Main Results:
- Higher median AUC0-24 observed compared to non-ECMO patients.
- Increased volume of distribution (Vd) suggests drug sequestration.
- Factors like obesity and hypoalbuminemia impact drug exposure.
Conclusions:
- Isavuconazole PK exhibits significant variability in ECMO patients.
- Increased AUC and Vd, with altered clearance, necessitate tailored dosing.
- Further research needed to optimize Isavuconazole therapy during ECMO.
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