Anidulafungin dosing in critically ill patients with continuous venovenous haemodiafiltration.
BACKGROUND
Anidulafungin is indicated as a first-line treatment for invasive candidiasis in critically ill patients. In the intensive care unit, sepsis is the main cause of acute renal failure, and treatment with continuous renal replacement therapy (CRRT) has increased in recent years. Antimicrobial pharmacokinetics is affected by CRRT, but few studies have addressed the optimal dosage for anidulafungin during CRRT.


METHODS
We included 12 critically ill patients who received continuous venovenous haemodiafiltration to treat acute renal failure. Anidulafungin was infused on 3 consecutive days, starting with a loading dose (200 mg) on Day 1, and doses of 100 mg on Days 2 and 3. Blood and ultradiafiltrate samples were collected on Day 3 (during steady-state) before, and at regular intervals after, the infusion had started. Anidulafungin concentrations were determined with HPLC.


RESULTS
On Day 3, peak plasma concentrations with the 100 mg dose were 6.2 ± 1.7 mg/L and 7.1 ± 1.9 mg/L in the arterial and venous samples, respectively. The mean, pre-filter trough concentration was 3.0 ± 0.6 mg/L. The mean AUC0-24 values for plasma anidulafungin were 93.9 ± 19.4 and 104.1 ± 20.3mg·h/L in the arterial and venous samples, respectively. There was no adsorption to synthetic surfaces, and the anidulafungin concentration in the ultradiafiltrate was below the limit of detection.


CONCLUSIONS
The influence of CRRT on anidulafungin elimination appeared to be negligible. Therefore, we recommend no adjustments to the anidulafungin dose for patients receiving CRRT.
Surgical Intensive Care Unit, Department of Anesthesiology and Intensive Care, Hospital Clínico Universitario de Valencia, Valencia, Spain gerardo.aguilar@uv.es.
Gerardo
G
Aguilar
Department of Clinical Pharmacology, University of Navarra Clinic, Pamplona, Spain.
José Ramón
JR
Azanza
Surgical Intensive Care Unit, Department of Anesthesiology and Intensive Care, Hospital Clínico Universitario de Valencia, Valencia, Spain.
José A
JA
Carbonell
Surgical Intensive Care Unit, Department of Anesthesiology and Intensive Care, Hospital Clínico Universitario de Valencia, Valencia, Spain.
Carlos
C
Ferrando
Surgical Intensive Care Unit, Department of Anesthesiology and Intensive Care, Hospital Clínico Universitario de Valencia, Valencia, Spain.
Rafael
R
Badenes
Department of Clinical Pharmacology, University of Navarra Clinic, Pamplona, Spain.
María Asunción
MA
Parra
Department of Clinical Pharmacology, University of Navarra Clinic, Pamplona, Spain.
Belén
B
Sadaba
Department of Microbiology, Hospital Clínico Universitario de Valencia, Valencia, Spain School of Medicine, University of Valencia, Valencia, Spain.
David
D
Navarro
Surgical Intensive Care Unit, Department of Anesthesiology and Intensive Care, Hospital Clínico Universitario de Valencia, Valencia, Spain.
Jaume
J
Puig
Surgical Intensive Care Unit, Department of Anesthesiology and Intensive Care, Hospital Clínico Universitario de Valencia, Valencia, Spain.
Amanda
A
Miñana
Surgical Intensive Care Unit, Department of Anesthesiology and Intensive Care, Hospital Clínico Universitario de Valencia, Valencia, Spain.
Carlos
C
Garcia-Marquez
Surgical Intensive Care Unit, Department of Anesthesiology and Intensive Care, Hospital Clínico Universitario de Valencia, Valencia, Spain.
Gergana
G
Gencheva
Surgical Intensive Care Unit, Department of Anesthesiology and Intensive Care, Hospital Clínico Universitario de Valencia, Valencia, Spain.
Andrea
A
Gutierrez
Surgical Intensive Care Unit, Department of Anesthesiology and Intensive Care, Hospital Clínico Universitario de Valencia, Valencia, Spain.
Francisco J
FJ
Marti
Surgical Intensive Care Unit, Department of Anesthesiology and Intensive Care, Hospital Clínico Universitario de Valencia, Valencia, Spain School of Medicine, University of Valencia, Valencia, Spain.
F Javier
FJ
Belda
D000077612:Anidulafungin; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002175:Candida / Q000187:drug effects / Q000302:isolation & purification; D058365:Candidiasis, Invasive / Q000188:drug therapy / Q000382:microbiology; D016638:Critical Illness / Q000628:therapy*; D054714:Echinocandins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017583:Hemodiafiltration / Q000009:adverse effects; D006801:Humans; D007362:Intensive Care Units
D000935:Antifungal Agents; D054714:Echinocandins; D000077612:Anidulafungin
acute renal failure; echinocandins; renal replacement therapy