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- Title
Isavuconazole Pharmacokinetics in Critically Ill Patients: Relationship with Clinical Effectiveness and Patient Safety.
- Authors
Martín-Cerezuela, María; Maya Gallegos, Cristina; Marqués-Miñana, María Remedios; Broch Porcar, María Jesús; Cruz-Sánchez, Andrés; Mateo-Pardo, Juan Carlos; Peris Ribera, José Esteban; Gimeno, Ricardo; Castellanos-Ortega, Álvaro; Poveda Andrés, José Luis; Ramírez Galleymore, Paula
- Abstract
Isavuconazole is used to treat fungal infections. This study aims to describe isavuconazole pharmacokinetics in critically ill patients and evaluate their relationship with clinical efficacy and patient safety. We conducted a prospective, observational study in patients treated with intravenous isavuconazole. Samples were collected at predose (Cmin), 1 h (Cmax) and 12 h (C50) after the last dose. The plasma concentration was determined by high-performance liquid chromatography. The relationship between plasma concentration and clinical and microbiological outcomes and safety was evaluated. The influence of covariates (age, sex, weight, SAPS3, creatinine, liver enzymes and extracorporeal devices: continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO)) was analysed. Population pharmacokinetic modelling was performed using NONMEN®. A total of 71 isavuconazole samples from 24 patients were analysed. The mean Cmin was 1.76 (1.02) mg/L; 87.5% reached the optimal therapeutic target and 12.5% were below 1 mg/L. Population pharmacokinetics were best described by a one-compartment model with first-order elimination. No factor had a significant impact on the plasma concentration or pharmacokinetic parameters. Thus, isavuconazole could be safely used in a critically ill population, even in those treated with CRRT and ECMO, from a pharmacokinetic standpoint. Therefore, routine therapeutic drug monitoring may not be strictly necessary in daily clinical practice.
- Subjects
DRUG monitoring; EXTRACORPOREAL membrane oxygenation; HIGH performance liquid chromatography; RENAL replacement therapy; LIVER enzymes
- Publication
Antibiotics (2079-6382), 2024, Vol 13, Issue 8, p706
- ISSN
2079-6382
- Publication type
Case Study
- DOI
10.3390/antibiotics13080706