Posaconazole Pharmacokinetics, Safety, and Tolerability in Subjects With Varying Degrees of Chronic Renal Disease

Abstract

Posaconazole is a triazole antifungal in development for the treatment of invasive fungal infections. The authors evaluated the pharmacokinetics and safety of posaconazole in healthy subjects and in those with mild (CL_CR = 50–80 mL/min), moderate (CL_CR = 20–49 mL/min), and severe chronic renal disease (CL_CR .130). Mean CL/F values before and during hemodialysis were comparable. Furthermore, the difference in the predialyzed and postdialyzed posaconazole concentrations was only ∼3%, supporting that posaconazole was not removed by hemodialysis. Protein binding was similar in all groups (∼98%) and was unaffected by hemodialysis. Posaconazole was generally well tolerated. One patient had elevated liver function test results that were not present at baseline and were thought to be possibly related to posaconazole. Results of this single‐dose study indicate that dosage adjustments for patients with varying degrees of renal disease are not required.