title: Individual dose adjustment of oral busulfan using a test dose in hematopoietic stem cell transplantation.
abstract: Maintaining the appropriate average steady-state plasma concentrations (Css) of busulfan (BU) is critical for both successful engraftment and minimizing toxicity in hematopoietic stem cell transplantation (HST). We therefore performed a prospective trial with 50 adult Japanese patients that involved adjusting the BU dose in accordance with individual BU pharmacokinetics (PK). After administering a 0.5-mg/kg test dose of oral BU, we analyzed individual BU PK parameters and calculated an adjusted BU dose that would achieve a target BU Css of 850 ng/mL. Thirty-nine patients (78%) required a BU dose decrease, and the median adjusted BU dose was 0.81 mg/kg (range, 0.51-1.29 mg/kg). All patients who underwent allogeneic HST received the adjusted BU dose. After administering the sixth BU dose, we measured the plasma BU concentration. The actual BU concentration was significantly correlated with the expected BU concentration, and the predictability of the BU Css was 103% +/- 9%. The incidence of toxicity excluding oral mucositis was low, and there was no regimen-related toxicity-associated mortality. Engraftment was achieved in 98% of the patients. This study showed that our method for adjusting the BU dose facilitated reliable prediction of the actual BU Css and that individualized BU dose adjustment was able to improve clinical outcomes in HST recipients treated with a BU-containing conditioning regimen.
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan. yasushi@fukuoka-u.ac.jp
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takamatsu
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sasaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Eto
authors.forename: Koji
authors.initials: K
authors.lastname: Nagafuji
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Abe
authors.forename: Ilseung
authors.initials: I
authors.lastname: Choi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ogata
authors.forename: Shuuji
authors.initials: S
authors.lastname: Hara
authors.forename: Junji
authors.initials: J
authors.lastname: Suzumiya
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
mesh_terms: D000284:Administration, Oral; D000328:Adult; D044466:Asian People; D002066:Busulfan / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000009:adverse effects / Q000493:pharmacokinetics*; D011446:Prospective Studies; D013280:Stomatitis / Q000139:chemically induced; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D019653:Myeloablative Agonists; D002066:Busulfan