Pharmacokinetics of itraconazole oral solution in allogeneic bone marrow transplant patients receiving total body irradiation

Abstract

A prospective study of the pharmacokinetics of itra- conazole solution was performed in 11 patients who underwent allogeneic BMT (day of BMT = day 0) after a conditioning regimen including total body irradiation (TBI). Itraconazole solution (400 mg once a day) was given 7 days before BMT and continued up to the end of neutropenia unless another antifungal treatment was necessary. Blood samples were collected before itraconazole intake (C_min) and 4 h later (C_max) every other day for assays of itraconazole (ITRA) and its active metabolite hydroxy-itraconazole (OH-ITRA). The mean values of C_min ITRA and OH-ITRA, respectively, were 287 ± 109 ng/ml and 629 ± 227 ng/ml at day −1 and 378 ± 147 ng/ml and 725 ± 242 ng/ml at day +1. The maximum C_min values were observed at day +3. Six patients at day −1 (54%) and 8 at day +1 (72%) had satisfactory residual plasma concentrations of at least 250 ng/ml of unchanged ITRA. From day +1 to day +9, eight patients discontinued the itraconazole treatment, five of them had satisfactory plasma residual concentrations at this time. This work shows a good bioavailability of itraconazole oral solution during the early phase after allogeneic BMT, but more data are needed for the late phases.