TY - JOUR
T1 - Pharmacokinetics study of once-daily intravenous busulfan in conditioning regimens for hematopoietic stem cell transplantation
AU - Sato, Miki
AU - Kako, Shinichi
AU - Matsumoto, Kana
AU - Oshima, Kumi
AU - Akahoshi, Yu
AU - Nakano, Hirofumi
AU - Ugai, Tomotaka
AU - Yamasaki, Ryoko
AU - Wada, Hidenori
AU - Ishihara, Yuko
AU - Sakamoto, Kana
AU - Kawamura, Koji
AU - Ashizawa, Masahiro
AU - Terasako-Saito, Kiriko
AU - Kimura, Shun Ichi
AU - Nakasone, Hideki
AU - Kikuchi, Misato
AU - Tanihara, Aki
AU - Yamazaki, Rie
AU - Tanaka, Yukie
AU - Kanda, Junya
AU - Nishida, Junji
AU - Morita, Kunihiko
AU - Kanda, Yoshinobu
N1 - Publisher Copyright:
© 2015, The Japanese Society of Hematology.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - In Japan, intravenous busulfan (ivBu) is usually given four times per day as an infusion at 0.8 mg/kg over 2 h. However, as this requires a midnight administration, a once-daily infusion of ivBu at 3.2 mg/kg over 3 h has been investigated as a more convenient and safer method. In this study, 20 Japanese patients received once-daily ivBu in conditioning regimens before allogeneic hematopoietic stem cell transplantation (HSCT), and blood samples were obtained just before, and 3, 3.5, 5, 7, 10, and 24 h after the initiation of ivBu infusion. The outcomes of HSCT were evaluated prospectively. The median area under the plasma concentration versus time curve (AUC) of Bu was 5272 μmol × min/L (range 3491–6284 μmol × min/L), and was similar to those in previous once-daily ivBu studies and to the estimated daily AUC in previous 4-times-daily ivBu studies. All of the patients but two, who died early due to infection, achieved neutrophil engraftment at a median of 25 days after transplantation. No patient was diagnosed with veno-occlusive disease according to the criteria established by Jones. No regimen-related toxicity was significantly associated with AUC. In conclusion, once-daily administration of ivBu has a stable pharmacokinetic profile, and was safely performed in Japanese patients.
AB - In Japan, intravenous busulfan (ivBu) is usually given four times per day as an infusion at 0.8 mg/kg over 2 h. However, as this requires a midnight administration, a once-daily infusion of ivBu at 3.2 mg/kg over 3 h has been investigated as a more convenient and safer method. In this study, 20 Japanese patients received once-daily ivBu in conditioning regimens before allogeneic hematopoietic stem cell transplantation (HSCT), and blood samples were obtained just before, and 3, 3.5, 5, 7, 10, and 24 h after the initiation of ivBu infusion. The outcomes of HSCT were evaluated prospectively. The median area under the plasma concentration versus time curve (AUC) of Bu was 5272 μmol × min/L (range 3491–6284 μmol × min/L), and was similar to those in previous once-daily ivBu studies and to the estimated daily AUC in previous 4-times-daily ivBu studies. All of the patients but two, who died early due to infection, achieved neutrophil engraftment at a median of 25 days after transplantation. No patient was diagnosed with veno-occlusive disease according to the criteria established by Jones. No regimen-related toxicity was significantly associated with AUC. In conclusion, once-daily administration of ivBu has a stable pharmacokinetic profile, and was safely performed in Japanese patients.
KW - Area under the plasma concentration versus time curve
KW - Conditioning regimen
KW - Hematopoietic stem cell transplantation
KW - Once-daily intravenous busulfan
KW - Pharmacokinetics
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U2 - 10.1007/s12185-015-1756-6
DO - 10.1007/s12185-015-1756-6
M3 - Article
C2 - 25672602
AN - SCOPUS:84939953140
VL - 101
SP - 497
EP - 504
JO - International Journal of Hematology
JF - International Journal of Hematology
SN - 0925-5710
IS - 5
ER -