Population pharmacokinetics of itraconazole solution used as prophylaxis for febrile neutropenia

Abstract

Although administration of antifungal agents, such as itraconazole (ITC) solution, for prophylaxis is the most promising strategy for the treatment of haematological malignancies, little is known about the population pharmacokinetic (PK) parameters. A clinical study was conducted to identify PK parameters for the administration of 200 mg/day ITC solution used as prophylaxis for febrile neutropenia in patients undergoing treatment. The study population comprised six patients. NONMEM software was used to estimate PK parameters. Clearance, volume of distribution and the absorption rate constant were 12.7 L/h, 333 L and 1.72 h −1, respectively. These parameters were different from a previous study to large extent, which may be due to differences in intended patients. These differences strongly suggest that establishment of population pharmacokinetics is essential for planning a prospective clinical trial. Assuming a normal distribution, we predicted the trough concentrations of 94.5% of the patients receiving 200 mg/day ITC solution to be >250 ng/mL, indicating that administration of 200 mg/day might be suitable for prophylaxis. This pilot study presents a basic PK model of ITC solution in Japanese haematological patients for the establishment of optimal administration. Large-scale studies will be necessary in the future to determine population PK parameters with covariates.