Anidulafungin pharmacokinetics in critically ill patients

Objectives: Early antifungal treatment with adequate drug exposure reduces mortality in patients with candidemia. Efficacy of anidulafungin is driven by AUC (area under the curve)/MIC ratio. As anidulafungin clearance is ∼30% higher in patients with invasive candidiasis than in patients with oesophageal candidiasis patients at the ICU may be at risk for underexposure. Therefore, insight in anidulafungin pharmacokinetics in a “real-life” population of critically ill patients is important. Methods: We conducted a prospective open-label study in adult patients admitted to an intensive care unit between June 2010 and November 2011. Patients were eligible for inclusion in case of a positive culture for Candida from a sterile site - blood or intraabdominal fluid. Blood samples were taken just before administering anidulafungin and at 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after start of infusion on day 3 or 4 of treatment. Anidulafungin plasma concentrations were measured with a validated LC-MS/MS method. The AUC was calculated using a non compartmental method. Results: Twenty patients with a median age of 71 (IQR: 60-75) were studied; 11 males and 9 females. Cultures for Candida were positive in blood for seven patients and in intra-abdominal fluid for 13 patients. In comparison with previously reported data of critically ill patients, we observed an apparent lower exposure and clearance and longer half-life in our patients, see Table. The volume of distribution was similar. MIC values ranged from