Laura Doménech-Moral, Sonia García-García, Alba Pau-Parra, Manuel Sosa, Adrian Puertas Sanjuan, Camilo Bonilla, Elisabeth Gallart, Laura Castellote, Patricia Faixó, Jessica Guevara, Albert Vilanova, María Martínez-Pla, Aldair Conto, Xavier Nuvials, Pilar Lalueza, Ricard Ferrer, Maria Queralt Gorgas, Jordi Riera
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引用次数: 0
Abstract
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.
Antibiotics-BaselPharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics
CiteScore
7.30
自引率
14.60%
发文量
1547
审稿时长
11 weeks
期刊介绍:
Antibiotics (ISSN 2079-6382) is an open access, peer reviewed journal on all aspects of antibiotics. Antibiotics is a multi-disciplinary journal encompassing the general fields of biochemistry, chemistry, genetics, microbiology and pharmacology. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on the length of papers.