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Two-point limited sampling strategy is necessary to estimate the area under the concentration-time curve for intravenous busulfan in infants and young children
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  • Tomoyuki Utano,
  • Motohiro Kato,
  • Kenichi Sakamoto,
  • Tomoo Osumi,
  • Kana Matsumoto,
  • Kimikazu Matsumoto,
  • Akimasa Yamatani
Tomoyuki Utano
National Center for Child Health and Development

Corresponding Author:[email protected]

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Motohiro Kato
National Center for Child Health and Development
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Kenichi Sakamoto
National Center for Child Health and Development
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Tomoo Osumi
National Center for Child Health and Development
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Kana Matsumoto
Doshisha Women's College of Liberal Arts
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Kimikazu Matsumoto
National Center for Child Health and Development
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Akimasa Yamatani
National Center for Child Health and Development
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Abstract

Background: Therapeutic drug monitoring for busulfan is important to prevent adverse events and improve outcomes in stem cell transplantation. We investigated intravenous busulfan pharmacokinetics and evaluated the utility of limited sampling strategy (LSS) as a simple method to estimate the area under the concentration-time curve (AUC). Procedure: The study comprised 87 busulfan measurements in 54 children who received intravenous busulfan between August 2015 and May 2020. AUCs were calculated from 3–5 blood sampling points in each patient, and the correlation between AUC and plasma concentrations (ng/mL) at 1, 2, 3, 4, and 6 h after initiating busulfan infusion (C1, C2, C3, C4, and C6, respectively). Results: By one-point sampling strategy, the most accurate predicted AUC was based on C6 (r2 = 0.789; precision, 11.0%) in all patients. The predicted AUC based on C6 was highly precise (r2 = 0.937; precision, 5.9%) in adolescent patients weighing > 23 kg, but the correlation was poor in infants and young children weighing ≤23 kg (r2 = 0.782; precision, 11.4%). By two-point sampling strategy, the predicted AUC based on C3 and C6 showed the most favorable performance (r2 = 0.943; precision, 6.4%), even in infants and young children, whereas the predicted AUC based on C3 and C6 was acceptable (r2 = 0.963; precision, 5.7%). Conclusions: The AUC of busulfan can be predicted based on C6 in adolescent patients. However, there was substantial inter-individual variation in busulfan pharmacokinetics in infants and young children, in whom two-point LSS was necessary for accurate AUC prediction.
05 Feb 2021Submitted to Pediatric Blood & Cancer
05 Feb 2021Submission Checks Completed
05 Feb 2021Assigned to Editor
08 Feb 2021Reviewer(s) Assigned
21 Feb 2021Review(s) Completed, Editorial Evaluation Pending
21 Feb 2021Editorial Decision: Revise Minor
12 Mar 20211st Revision Received
12 Mar 2021Assigned to Editor
12 Mar 2021Submission Checks Completed
13 Mar 2021Reviewer(s) Assigned
27 Mar 2021Review(s) Completed, Editorial Evaluation Pending
29 Mar 2021Editorial Decision: Revise Minor
30 Mar 2021Assigned to Editor
30 Mar 20212nd Revision Received
30 Mar 2021Submission Checks Completed
02 Apr 2021Review(s) Completed, Editorial Evaluation Pending
02 Apr 2021Editorial Decision: Accept