title: Personalized busulfan and treosulfan conditioning for pediatric stem cell transplantation: the role of pharmacogenetics and pharmacokinetics.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: M H
authors.initials: MH
authors.lastname: ten Brink
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Zwaveling
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Swen
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: R G M
authors.initials: RG
authors.lastname: Bredius
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: A C
authors.initials: AC
authors.lastname: Lankester
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: h.j.guchelaar@lumc.nl.
authors.forename: H J
authors.initials: HJ
authors.lastname: Guchelaar
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D002066:Busulfan / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D016903:Drug Monitoring; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D011110:Polymorphism, Genetic; D057285:Precision Medicine
chemical_list: D018906:Antineoplastic Agents, Alkylating; C018404:treosulfan; D002066:Busulfan