Pharmacokinetics of anidulafungin in critically ill intensive care unit patients with suspected or proven invasive fungal infections

Echinocandins, such as anidulafungin, are the first-line treatment for candidemia or invasive candidiasis in critically ill patients. There are conflicting data on the pharmacokinetic properties of anidulafungin in intensive care unit (ICU) patients. Adult ICU patients (from 3 hospitals) receiving anidulafungin for suspected or proven fungal infections were included in the present study. Patients were considered evaluable if a pharmacokinetic curve for day 3 could be completed. Twenty-three of 36 patients (7 female and 16 male) were evaluable. The median (range) age and body weight were 66 (28 to 88) years and 76 (50 to 115) kg, respectively. Pharmacokinetic sampling on day 3 (n = 23) resulted in a median anidulafungin area under the concentration-time curve from 0 to 24 h (AUC0-24) of 72.1 (interquartile range [IQR], 61.3 to 94.0) mg·h·liter-1, a median daily trough concentration (C24) of 2.2 (IQR, 1.9 to 2.9) mg/liter, a median maximum concentration of drug in serum (Cmax) of 5.3 (IQR, 4.1 to 6.0) mg/liter, a median volume of distribution (V) of 46.0 (IQR, 32.2 to 60.2) liters, and a median clearance (CL) of 1.4 (IQR, 1.1 to 1.6) liters·h-1. Pharmacokinetic sampling on day 7 (n = 13) resulted in a median AUC0-24 of 82.7 (IQR, 73.0 to 129.5) mg·h·liter-1, a median minimum concentration of drug in serum (Cmin) of 2.8 (IQR, 2.2 to 4.2) mg/liter, a median Cmax of 5.9 (IQR, 4.6 to 8.0) mg/liter, a median V of 39.7 (IQR, 32.2 to 54.4) liters, and a median CL of 1.2 (IQR, 0.8 to 1.4) liters·h-1. The geometric mean ratio for the AUCday7/AUCday3 term was 1.13 (90% confidence interval [CI], 1.03 to 1.25). The exposure in the ICU patient population was in accordance with previous reports on anidulafungin pharmacokinetics in ICU patients but was lower than that for healthy volunteers or other patient populations. Larger cohorts of patients or pooled data analyses are necessary to retrieve relevant covariates. (This study has been registered at ClinicalTrials.gov under identifier NCT01438216.)

Pharmacokinetics of Anidulafungin in critically ill patients in the Intensive Care Unit with suspected or proven invasive fungal infections

Echinocandins, such as anidulafungin are first line treatment for candidemia or invasive candidiasis in critically ill patients. There is conflicting data on the pharmacokinetic properties of anidulafungin in ICU patients. Adult ICU patients (from 3 hospitals) receiving anidulafungin for suspected or proven fungal infections were included. Patient were considered evaluable when a pharmacokinetic curve on day 3 could be completed. 23 out of 36 patients (7 female, 16 male) were evaluable. Median (range) age and bodyweight were 66 (28-88) yr and 76 (50-115) kg. Pharmacokinetic sampling on day 3 (n=23) resulted in a median anidulafungin AUC0-24h of 72.1 (IQR 61.3-94.0) mg*h*L(-1), a median C24 of 2.2 (IQR 1.9-2.9) mg/L, a median Cmax of 5.3 (IQR 4.1-6.0) mg/L, a median Vd of 46.0 (IQR 32.2-60.2) L and a median CL of 1.4 (IQR 1.1-1.6) L*h-1. Pharmacokinetic sampling on day 7 (n=13) resulted in a median AUC0-24h of 82.7 (IQR 73.0 - 129.5) mg*h*L(-1), a median Cmin of 2.8 (IQR 2.2 - 4.2) mg/L, a median Cmax of 5.9 (IQR 4.6 - 8.0) mg/L, a median Vd of 39.7 (IQR 32.2 - 54.4) L and a median CL of 1.2 (IQR 0.8 - 1.4) L*h(-1) The Geometric Mean Ratio for AUCday7/AUCday3 was 1.13 (90% CI 1.03 - 1.25). The exposure in the ICU patient population was in accordance with previous reports on anidulafungin in ICU patients but was lower compared to healthy volunteers or other patient populations. Larger cohorts of patients or pooled data analyses are necessary to retrieve relevant covariates