Importance of plasma concentration monitoring of itraconazole in prophylactic oral administration for allogeneic haematopoietic stem cell transplantation

Ref ID: 18600

Author:

Y. Asano-Mori (1), H. Shimazu (1), K. Ishiwata (1), N. Nakano
(1), M. Tsuji (1), H. Yamamoto (1), N. Uchida (1), A. Wake (1),
S. Kishino (2), S. Taniguchi (1)

Author address:

(1)Toranomon Hospital (Tokyo, JP); (2)Meiji Pharmaceutical
University (Tokyo, JP)

Full conference title:

Annual Meeting of the EBMT, 36th

Abstract:

Objectives: Oral itraconazole (ITCZ) solution has been expected
to prevent invasive fungal infections (IFIs) more effectively than
capsule among allogeneic hematopoietic stem cell transplantation (HSCT) recipients, because of the superior bioavailability.
However, it remains unclear whether reliable serum concentrations are maintained by the oral ITCZ solution in all patients at
all times after HSCT. Therefore, we investigated the inter- and
intrapatient variability by serial evaluation of the plasma ITCZ
levels.
Patients and methods: Prophylactic administration of oral ITCZ
solution at a once daily dose of 200 mg started more than
10 days before HSCT in 19 allogeneic HSCT recipients. Eleven
patients received cord blood as the stem cell source, six grafts
from unrelated donors and two from related donors, respectively. Sixteen patients received fl udarabine-based reduced
intensity conditioning regimen and the remaining three received
the combination of TBI and cyclophosphamide (Cy) for conditioning. Patients continued prophylaxis with intravenous ITCZ at
200 mg/day, if oral medication was intolerable. Plasma samples
were obtained within three days prior to initiating calcineurin
inhibitors before HSCT, a week after HSCT and a month after
HSCT. Trough levels of ITCZ and hydroxy-ITCZ in plasma were
measured by using high-performance liquid chromatography.
Results: Median trough concentrations of ITCZ before HSCT,
a week after and a month after HSCT were 275.23 ng/mL
(range 8.00 to 2376.53 ng/mL), 297.88 ng/mL (range 37.90 to
1371.99 ng/mL), and 492.89 ng/mL (range 53.04 to 1185.17
ng/mL), respectively. Marked variations of ITCZ concentrations
were observed among individuals at different periods after
HSCT (Figure 1). The concentrations of > 250 ng/mL and > 500
ng/mL were achieved in 52.6% and 26.3% of patients before
HSCT, 52.6% and 42.1% a week after, and 66.7% and 58.3% a
month after HSCT. No serious adverse effect was observed in
all three patients who received the Cy-included regimen while
on ITCZ prophylaxis. One patient developed probable invasive
aspergillosis 23 days after HSCT, with the lower concentration
of 112.38 ng/mL one week after HSCT in spite of 438.77 ng/mL
before HSCT.
Conclusions: Plasma concentration monitoring of ITCZ warrants consideration in allogeneic HSCT recipients, because of
the marked inter- and intrapatient variability

Abstract Number: R1271

Conference Year: 2010

Link to conference website: NULL

New link: NULL

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