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Isavuconazole Pharmacokinetics in Critically Ill Patients: Relationship with Clinical Effectiveness and Patient
María Martín-Cerezuela1, Cristina Maya Gallegos2, María Remedios Marqués-Miñana1
1Pharmacy Unit, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain.
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.
Insights
Isavuconazole effectively treats fungal infections in critically ill patients. Pharmacokinetic analysis shows it can be safely used, even with extracorporeal support, suggesting routine drug monitoring may not be necessary.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Infectious Diseases
Background:
- Isavuconazole is a vital antifungal agent for treating invasive fungal infections.
- Critically ill patients often have altered pharmacokinetics, necessitating careful drug management.
- Understanding isavuconazole's behavior in this population is crucial for optimizing treatment.
Purpose of the Study:
- To characterize isavuconazole pharmacokinetics in critically ill patients.
- To assess the relationship between drug concentrations, clinical efficacy, and safety.
- To identify factors influencing isavuconazole levels, including extracorporeal support.
Main Methods:
- Prospective, observational study involving intravenous isavuconazole administration.
- Plasma samples collected at specific time points (Cmin, Cmax, C50) for concentration analysis via HPLC.
- Population pharmacokinetic modeling using NONMEN, analyzing covariates like age, organ function, and ECMO/CRRT.
Main Results:
- Analyzed 71 samples from 24 critically ill patients.
- Mean Cmin was 1.76 mg/L; 87.5% achieved therapeutic targets, while 12.5% fell below 1 mg/L.
- A one-compartment model best described pharmacokinetics; no significant covariate impact on concentrations was found.
Conclusions:
- Isavuconazole exhibits predictable pharmacokinetics in critically ill patients.
- The drug is safe and effective in this population, including those on CRRT and ECMO.
- Routine therapeutic drug monitoring for isavuconazole may not be essential in clinical practice.
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