Personalized busulfan and treosulfan conditioning for pediatric stem cell transplantation: the role of pharmacogenetics and pharmacokinetics.

Autor: ten Brink MH; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands., Zwaveling J; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands., Swen JJ; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands., Bredius RG; Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands., Lankester AC; Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands., Guchelaar HJ; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: h.j.guchelaar@lumc.nl.
Jazyk: angličtina
Zdroj: Drug discovery today [Drug Discov Today] 2014 Oct; Vol. 19 (10), pp. 1572-86. Date of Electronic Publication: 2014 Apr 16.
DOI: 10.1016/j.drudis.2014.04.005
Abstrakt: Busulfan- and treosulfan-based conditionings are the cornerstone of pediatric allogeneic hematopoietic stem cell transplantation (HSCT). Although both drugs are alkylating agents, their mechanisms of action, pharmacokinetics (PK) and toxicity profiles are different. Experience with busulfan in pediatric HSCT is broad and the knowledge on the pharmacodynamics (PD), PK and, to a lesser extent, pharmacogenetics (PG) has resulted in a more effective therapy. Treosulfan has only recently been introduced in pediatric HSCT and is considered a promising new therapy because of its beneficial toxicity profile. However, knowledge of the PK and PG of treosulfan is limited. In this review, we describe the pharmacology of both agents and discuss factors causing variability in PK in relation to therapeutic outcome in HSCT.
(Copyright © 2014 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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