Pharmacokinetics and Dialytic Clearance of Isavuconazole during In Vitro and In Vivo Continuous Renal Replacement Therapy

The pharmacokinetics (PK) and dialytic clearance of isavuconazole in vitro and in 7 solid-organ transplant patients undergoing continuous renal replacement therapy (CRRT) were evaluated. In vivo, the mean (+/- standard deviation [SD]) plasma PK parameters of isavuconazole were as follows: maximum concentration of drug in serum (C-max), 4.00 +/- 1.45 mg/liter; minimum concentration of drug in serum (C-min), 1.76 +/- 0.76 mg/liter; half-life (t(1/2)), 48.36 +/- 29.78 h; volume of distribution at steady state (V-ss), 288.78 +/- 182.11 liters, clearance at steady state (CLss), 4.85 +/- 3.79 liters/h; and area under the concentration-time curve (AUC), 54.01 +/- 20.98 mg . h/liter. Transmembrane clearance represented just 0.7% of the total isavuconazole clearance. These data suggest that isavuconazole is not readily removed by CRRT and no dose adjustments are necessary.