Busulfan dose Recommendation in Inherited Metabolic Disorders: Population Pharmacokinetic Analysis.

Autor: Takahashi T; Division of Pediatric Blood and Marrow Transplant, University of Minnesota, Minneapolis, Minnesota; Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota. Electronic address: takah033@umn.edu., Illamola SM; Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota., Jennissen CA; Department of Pharmacy, Fairview MHealth, Minneapolis, Minnesota., Long SE; Department of Pharmacy, Fairview MHealth, Minneapolis, Minnesota., Lund TC; Division of Pediatric Blood and Marrow Transplant, University of Minnesota, Minneapolis, Minnesota., Orchard PJ; Division of Pediatric Blood and Marrow Transplant, University of Minnesota, Minneapolis, Minnesota., Gupta AO; Division of Pediatric Blood and Marrow Transplant, University of Minnesota, Minneapolis, Minnesota., Long-Boyle JR; Departments of Clinical Pharmacy, University of California San Francisco, Mission Bay, California; Division of Pediatric Allergy/Immunology/Bone Marrow Transplantation, University of California San Francisco, Mission Bay, California.
Jazyk: angličtina
Zdroj: Transplantation and cellular therapy [Transplant Cell Ther] 2022 Feb; Vol. 28 (2), pp. 104.e1-104.e7. Date of Electronic Publication: 2021 Dec 06.
DOI: 10.1016/j.jtct.2021.11.018
Abstrakt: Busulfan is a commonly used alkylating agent in the conditioning regimens of hematopoietic cell transplantation (HCT). Population pharmacokinetic (popPK) models enable description of busulfan PK and optimization of exposure, which leads to improvement of event-free survival after HCT. Prior busulfan popPK analysis has been limited by small numbers in patients with inherited metabolic disorders (IMD). The primary objective was to characterize population PK of busulfan in a large cohort of children and young adults undergoing HCT for IMD. PopPK analysis of busulfan drug concentrations was performed using data from 78 patients with IMD who received intravenous busulfan (every 24 hours, 4 doses) as part of pretransplantation combination chemotherapy. The final model for busulfan drug clearance was used to estimate individual doses aimed to achieve a target cumulative area under the curve (cAUC) of 80 to 100 mg · h/L. We then compared the probability of cAUC within the range of 80 to 100 mg · h/L by the developed dosing regimen versus conventional regimen. A 1-compartment, linear elimination model best described the PK of busulfan. Significant covariates demonstrated to affect busulfan clearance included total body weight and the time (in days) from busulfan infusion start. The probability of target cAUC attainment by the developed dosing versus the conventional dosing were 47% versus 43% for body weight <12 kg, and 48% versus 36% for body weight ≥12 kg. We described population PK of intravenous busulfan in a large IMD cohort. The proposed dosing regimen based on the developed model can improve the target cAUC attainment of busulfan for IMD.
(Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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