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Accurate Prediction of Initial Busulfan Exposure Using a Test Dose With 2‐ and 6‐Hour Blood Sampling in Adult Patients Receiving a Twice‐Daily Intravenous Busulfan‐Based Conditioning Regimen
Author(s) -
Huang Jingjing,
Li Ziwei,
Liang Wu,
Chen Bing,
Hu Jiong,
Yang Wanhua
Publication year - 2019
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.1354
Subject(s) - busulfan , medicine , area under the curve , population , mean squared error , mathematics , sampling (signal processing) , blood sampling , nuclear medicine , statistics , urology , hematopoietic stem cell transplantation , transplantation , environmental health , filter (signal processing) , computer science , computer vision
This study aimed to predict the area under the curve (AUC) of the initial busulfan dose using a test dose with the sparse sampling scheme in adult patients who underwent hematopoietic cell transplant. A test dose of 0.8 mg/kg busulfan was used 2 days before twice‐daily intravenous busulfan‐based conditioning regimens were administered. The AUC and the clearance (CL) were calculated for both the test dose and the first dose (AUC T , CL T , AUC 1, and CL 1 ) by noncompartmental analysis. The sparse sampling schemes of the test dose were developed by Bayesian method based on the population pharmacokinetic model. The optimal sparse sampling schemes were determined by evaluating the mean prediction error, the root mean square error, the absolute mean prediction error, and Bland‐Altman plot. The mean AUC 1 was 7.20 ± 1.48 mg • h/L, which ranged from 4.70 to 9.46 mg • h/L. The AUC 1 was below the therapeutic concentration of 7.38 mg • h/L in 45% (9 of 20) of the patients. The CL T of 3.05 ± 0.56 mL/min/kg was not significantly different with the CL 1 of 3.03 ± 0.69 mL/min/kg ( P = .901). A sampling scheme at 2 and 6 hours after the test dose was developed to predict the AUC T (mean prediction error of 1.64%, root mean square error of 6.17%, and absolute mean prediction error of 4.94%). Additionally, the Bland‐Altman plot showed that the 2‐sampling scheme provided an acceptably accurate prediction of the AUC 1 . A test dose with a 2‐sampling scheme was sufficient to personalize the initial busulfan dosing in hematopoietic cell transplant recipients.