Related Experiment Video
Updated: Oct 16, 2025
Observational Study Protocol for Repeated Clinical Examination and Critical Care Ultrasonography Within the Simple Intensive Care Studies
Published on: January 16, 2019
Voriconazole Pharmacokinetics Are Not Altered in Critically Ill Patients with Acute-on-Chronic Liver Failure and
Jörn Grensemann1, Christoph Pfaffendorf2, Sebastian G Wicha2
1Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
Abstract:
Infection and sepsis are a main cause of acute-on-chronic liver failure (ACLF). Besides bacteria, molds play a role. Voriconazole (VRC) is recommended but its pharmacokinetics (PK) may be altered by ACLF. Because ACLF patients often suffer from concomitant acute renal failure, we studied the PK of VRC in patients receiving continuous renal replacement therapy (RRT) with ACLF and compared it to PK of VRC in critically ill patients with RRT without concomitant liver failure (NLF). In this prospective cohort study, patients received weight-based VRC. Pre- and post-dialysis membrane, and dialysate samples obtained at different time points were analyzed by high-performance liquid chromatography. An integrated dialysis pharmacometric model was used to model the available PK data. The recommended, 50% lower, and 50% higher doses were analyzed by Monte-Carlo simulation (MCS) for day 1 and at steady-state with a target trough concentration (TC) of 0.5-3mg/L. Fifteen patients were included in this study. Of these, 6 patients suffered from ACLF. A two-compartment model with linear clearance described VRC PK. No difference for central (V1) or peripheral (V2) volumes of distribution or clearance could be demonstrated between the groups. V1 was 80.6L (95% confidence interval: 62.6-104) and V2 106L (65-166) with a body clearance of 4.7L/h (2.87-7.81) and RRT clearance of 1.46L/h (1.29-1.64). MCS showed TC below/within/above target of 10/74/16% on day 1 and 9/39/52% at steady-state for the recommended dose. A 50% lower dose resulted in 26/72/1% (day 1) and 17/64/19% at steady-state and 7/57/37% and 7/27/67% for a 50% higher dose. VRC pharmacokinetics are not significantly influenced by ACLF in critically ill patients who receive RRT. Maintenance dose should be adjusted in both groups. Due to the high interindividual variability, therapeutic drug monitoring seems inevitable.
Insights
Voriconazole pharmacokinetics are similar in acute-on-chronic liver failure (ACLF) patients with renal replacement therapy (RRT) and those without. Dose adjustments and therapeutic drug monitoring are crucial for optimal voriconazole (VRC) levels.
Area of Science:
- Pharmacology
- Nephrology
- Hepatology
Background:
- Infection and sepsis are leading causes of acute-on-chronic liver failure (ACLF), with molds contributing significantly.
- Voriconazole (VRC) is a recommended antifungal, but its pharmacokinetics (PK) may be affected by ACLF.
- ACLF patients often have concurrent acute renal failure, necessitating continuous renal replacement therapy (RRT).
Purpose of the Study:
- To investigate the PK of VRC in critically ill patients with ACLF undergoing RRT.
- To compare VRC PK between ACLF patients with RRT and critically ill patients with RRT but without liver failure (NLF).
- To evaluate VRC dosing strategies using Monte Carlo simulations.
Main Methods:
- Prospective cohort study involving critically ill patients receiving weight-based VRC.
- Analysis of VRC concentrations in pre- and post-dialysis samples and dialysate using high-performance liquid chromatography.
- Application of an integrated dialysis pharmacometric model and Monte Carlo simulations for dose analysis.
Main Results:
- VRC PK was adequately described by a two-compartment model with linear clearance.
- No significant differences in VRC volume of distribution or clearance were observed between ACLF and NLF groups.
- Monte Carlo simulations indicated suboptimal trough concentrations with the recommended VRC dose, necessitating dose adjustments and highlighting interindividual variability.
Conclusions:
- ACLF does not significantly alter VRC pharmacokinetics in critically ill patients undergoing RRT.
- Standard VRC maintenance doses require adjustment in both ACLF and NLF patients receiving RRT.
- Therapeutic drug monitoring is essential for optimizing VRC therapy due to high interindividual variability.
More Related Videos
08:44Continuous IV Infusion is the Choice Treatment Route for Arginine-vasopressin Receptor Blocker Conivaptan in Mice to Study Stroke-evoked Brain Edema
Published on: September 1, 2016
16:19Heterotopic Auxiliary Rat Liver Transplantation With Flow-regulated Portal Vein Arterialization in Acute Hepatic Failure
Published on: September 13, 2014
Related Concept Videos
01:30Continuous Renal Replacement Therapy
01:25Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant
01:26Extracorporeal Removal of Drugs: Continuous Renal Replacement Therapy
01:11Renal Failure: Dose Adjustments
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
01:08Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention