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Two‐point blood sampling is sufficient and necessary to estimate the area under the concentration‐time curve for intravenous busulfan in infants and young children
Author(s) -
Utano Tomoyuki,
Kato Motohiro,
Sakamoto Kenichi,
Osumi Tomoo,
Matsumoto Kana,
Tomizawa Daisuke,
Matsumoto Kimikazu,
Yamatani Akimasa
Publication year - 2021
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.29069
Subject(s) - busulfan , medicine , pharmacokinetics , area under the curve , therapeutic drug monitoring , blood sampling , sampling (signal processing) , adverse effect , urology , transplantation , hematopoietic stem cell transplantation , filter (signal processing) , computer science , computer vision
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 three to five 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 (C 1 , C 2 , C 3 , C 4 , and C 6 , respectively). Results By one‐point sampling strategy, the most relevant predicted AUC was based on C 6 ( r 2 = 0.789; precision, 11.0%) in all patients. The predicted AUC based on C 6 was acceptable ( r 2 = 0.937; precision, 5.9%) for adolescent patients weighing >23 kg, but the correlation was poor in infants and young children weighing ≤ 23 kg ( r 2 = 0.782; precision, 11.4%). By two‐point sampling strategy, the predicted AUC based on C 3 and C 6 showed the most relevant concentrations ( r 2 = 0.943; precision, 6.4%), even in infants and young children, whereas the predicted AUC based on C 3 and C 6 was acceptable ( r 2 = 0.963; precision, 5.7%). Conclusions The AUC of busulfan can be predicted based on C 6 in adolescent patients. However, there was substantial interindividual variation in busulfan pharmacokinetics in infants and young children, in whom two‐point LSS was necessary for accurate AUC prediction.