Pharmacokinetics of itraconazole oral solution in allogeneic bone marrow transplant patients receiving total body irradiation.
A prospective study of the pharmacokinetics of itraconazole 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 (Cmin) and 4 h later (Cmax) every other day for assays of itraconazole (ITRA) and its active metabolite hydroxy-itraconazole (OH-ITRA). The mean values of Cmin 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 Cmin 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.
Unité de Greffe de Moëlle Osseuse, Service d'Hematologie, Hôpital E Herriot, Lyon, France.
M
M
Michallet
F
F
Persat
N
N
Kranzhöfer
J C
JC
Levron
C
C
Prat
A
A
Belhabri
E
E
Chwetzoff
J P
JP
Le Moing
D
D
Fiere
M A
MA
Piens
D000284:Administration, Oral; D000328:Adult; D000935:Antifungal Agents / Q000493:pharmacokinetics*; D016026:Bone Marrow Transplantation; D005260:Female; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D012996:Solutions; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D000935:Antifungal Agents; D012996:Solutions; D017964:Itraconazole