Yamaguchi Atsushi, Hirabayashi Shinsuke, Niki Kazuko, Kagami Keisuke, Terashita Yukayo, Cho Yuko, Manabe Atsushi, Sugawara Mitsuru, Takekuma Yoh
Department of Pharmacy, Hokkaido University Hospital, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo, 060-8648, Japan.
Laboratory of Clinical Pharmaceutics and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo, 060-0812, Japan.
Int J Hematol. 2025 Feb;121(2):244-251. doi: 10.1007/s12185-024-03891-0. Epub 2024 Dec 3.
Therapeutic drug monitoring (TDM) of busulfan (BU) is useful for achieving the target area under the curve (AUC) because its effective plasma-concentration range is narrow. This preliminary observational study evaluated the pharmacokinetic (PK) parameters of BU administered four times daily or once daily to pediatric patients. The plasma concentrations were measured at both the test dose and first dose, and the doses on day 1 and days 2-4 were determined based on each TDM. A comparison of PK parameters between four-times-daily and once-daily administration was performed for both the test dose and first dose of BU. Of the 11 patients, five received four-times-daily BU and six received once-daily BU. The V for once-daily administration was higher than that for four-times-daily administration for the first dose but not for the test dose. The ratio of actual AUC for the first dose to estimated AUC guided by the test dose was lower with once-daily administration than with four-times-daily administration. These results indicate that the PK parameters of BU administered once daily are challenging to predict based on the TDM of the test dose. TDM should be considered on day 1 to achieve the target AUC, especially with once-daily administration.
由于白消安（BU）的有效血浆浓度范围较窄，因此对其进行治疗药物监测（TDM）有助于达到目标曲线下面积（AUC）。这项初步观察性研究评估了每日给药四次或每日给药一次的BU在儿科患者中的药代动力学（PK）参数。在试验剂量和首次剂量时均测量血浆浓度，并根据每次TDM确定第1天以及第2 - 4天的剂量。对BU的试验剂量和首次剂量分别进行了每日四次给药和每日一次给药的PK参数比较。11例患者中，5例接受每日四次的BU给药，6例接受每日一次的BU给药。首次剂量每日一次给药的V高于每日四次给药，但试验剂量时并非如此。首次剂量的实际AUC与试验剂量指导下的估计AUC之比，每日一次给药低于每日四次给药。这些结果表明，基于试验剂量的TDM来预测每日一次给药的BU的PK参数具有挑战性。为达到目标AUC，尤其是每日一次给药时，应在第1天考虑进行TDM。
