title: Pharmacokinetics study of once-daily intravenous busulfan in conditioning regimens for hematopoietic stem cell transplantation.
abstract: 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.
authors: Division of Hematology, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma, Omiya-ku, Saitama, Saitama, 330-8503, Japan.
authors: Miki
authors: M
authors: Sato
authors: Shinichi
authors: S
authors: Kako
authors: Kana
authors: K
authors: Matsumoto
authors: Kumi
authors: K
authors: Oshima
authors: Yu
authors: Y
authors: Akahoshi
authors: Hirofumi
authors: H
authors: Nakano
authors: Tomotaka
authors: T
authors: Ugai
authors: Ryoko
authors: R
authors: Yamasaki
authors: Hidenori
authors: H
authors: Wada
authors: Yuko
authors: Y
authors: Ishihara
authors: Kana
authors: K
authors: Sakamoto
authors: Koji
authors: K
authors: Kawamura
authors: Masahiro
authors: M
authors: Ashizawa
authors: Kiriko
authors: K
authors: Terasako-Saito
authors: Shun-Ichi
authors: S
authors: Kimura
authors: Hideki
authors: H
authors: Nakasone
authors: Misato
authors: M
authors: Kikuchi
authors: Aki
authors: A
authors: Tanihara
authors: Rie
authors: R
authors: Yamazaki
authors: Yukie
authors: Y
authors: Tanaka
authors: Junya
authors: J
authors: Kanda
authors: Junji
authors: J
authors: Nishida
authors: Kunihiko
authors: K
authors: Morita
authors: Yoshinobu
authors: Y
authors: Kanda
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002066:Busulfan / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood*; D007262:Infusions, Intravenous; D007564:Japan; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D011446:Prospective Studies; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D002066:Busulfan