Multiple-dose pharmacokinetics of anidulafungin during continuous venovenous haemofiltration

Abstract

Clinical studies support a role for anidulafungin as first-line treatment of invasive candidiasis in critically ill patients and postulate no need for dose adjustments in mild to severe renal failure. Although intensive care patients requiring renal replacement therapy are at particular risk of invasive fungal infection, no pharmacokinetic data on anidulafungin during continuous venovenous haemofiltration (CVVHF) are available. Ten patients with CVVHF due to acute renal failure were included. Anidulafungin was infused on 3 consecutive days starting with a loading dose of 200 mg on day 1, followed by doses of 100 mg on each of days 2 and 3. During the 72 h study phase of CVVHF, blood and ultrafiltrate samples were collected at corresponding times. Anidulafungin concentrations were determined by HPLC. Peak plasma concentrations were reached 3 h after the start of infusion and were 8.5±3.6 mg/L at the pre-filter port. The mean arterial area under the curve (AUC0-24) of the study population was 109.9±49.82 mg·h/L, the total clearance was 1.08±0.41 L/h, the volume of distribution was 41.97±22.64 L and the elimination half-life was 28.78±10.40 h. Anidulafungin was not filtered, but CVVHF resulted in a substance loss of ∼20%, due to adherence to synthetic surfaces. Pharmacokinetics of anidulafungin during CVVHF resembled findings in healthy adults and adults with fungal infections. Therefore we recommend a loading dose of 200 mg intravenous anidulafungin on the first day and 100 mg on consecutive treatment days in patients during CVVHF.