2015
DOI: 10.1007/s12185-015-1756-6
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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… Show more

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Cited by 10 publications
(7 citation statements)
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“…There is an increased incidence of adverse events such as sinusoidal obstruction syndrome/hepatic veno‐occlusive disease (SOS/VOD), pulmonary toxicity, and graft versus host disease (GVHD) at higher AUC of busulfan, and graft failure or disease relapse at lower AUC in pediatric and adult patients . Given that busulfan exhibits an exposure–response relationship and high pharmacokinetic (PK) variability, therapeutic drug monitoring (TDM) is recommended clinical practice for patients receiving high‐dose busulfan prior to transplantation, particularly in children …”
mentioning
confidence: 99%
See 1 more Smart Citation
“…There is an increased incidence of adverse events such as sinusoidal obstruction syndrome/hepatic veno‐occlusive disease (SOS/VOD), pulmonary toxicity, and graft versus host disease (GVHD) at higher AUC of busulfan, and graft failure or disease relapse at lower AUC in pediatric and adult patients . Given that busulfan exhibits an exposure–response relationship and high pharmacokinetic (PK) variability, therapeutic drug monitoring (TDM) is recommended clinical practice for patients receiving high‐dose busulfan prior to transplantation, particularly in children …”
mentioning
confidence: 99%
“…[3][4][5] Given that busulfan exhibits an exposure-response relationship and high pharmacokinetic (PK) variability, therapeutic drug monitoring (TDM) is recommended clinical practice for patients receiving high-dose busulfan prior to transplantation, particularly in children. [6][7][8][9] Busulfan is metabolized extensively in the liver via conjugation with glutathione, catalyzed by glutathione S-transferase (GST) enzymes, predominantly GSTA1. [10][11][12] GSTM1 and GSTT1 are also involved in busulfan metabolism but to a lesser extent ( Fig.…”
mentioning
confidence: 99%
“…(7) Sato et al compared the median area under the plasma concentration versus time curve for Q6 to Q24 and showed similar exposures between the two dosing frequencies. (25) Dosing based on actual versus adjusted weight were also explored with the two dosing schedules of Bu and demonstrated no significant differences in exposure between Q6 and Q24 Bu. Except that using adjusted weight to calculate pre-targeted doses required more frequent increments according to pharmacokinetics in both dosing schedules.…”
Section: Discussionmentioning
confidence: 99%
“…However, the therapeutic potential of this agent is compromised by unpredictable adverse events, as overdosing induces severe toxicity and underdosing potentially results in relapse or graft failure [3,4]. Although intravenous busulfan is considered to have a much more predictable pharmacokinetic profile than oral busulfan, there remains strong variation, particularly in children [5][6][7]. Therapeutic drug monitoring for appropriate dose adjustment is therefore recommended in all patients treated with regimens containing high-dose busulfan [8].…”
Section: Introductionmentioning
confidence: 99%