Individualizing busulfan dose in specific populations and evaluating the risk of pharmacokinetic drug-drug interactions.

IF 3.9 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2023-02-01 DOI:10.1080/17425255.2023.2192924

David Combarel, Julie Tran, Julia Delahousse, Gilles Vassal, Angelo Paci

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引用次数: 1

Abstract

Introduction: Busulfan is an alkylating agent widely used in the conditioning of hematopoietic stem cell transplantation possessing a complex metabolism and a large interindividual and intra-individual variability, especially in children. Combined with the strong rationale of busulfan PK/PD relationships, factors altering its clearance (e.g. weight, age, and GST-A genetic polymorphism mainly) can also affect clinical outcomes.

Areas covered: This review aims to provide an overview of the current knowledge on busulfan pharmacokinetics, its pharmacokinetics variabilities in pediatric populations, drug-drug interactions (DDI), and their consequences regarding dose individualization. This review was based on medical literature up until October 2021.

Expert opinion: To ensure effective busulfan exposure in pediatrics, different weight-based nomograms have been established to determine busulfan dosage and provided improved results (65-80% of patients correctly exposed). In addition to nomograms, therapeutic drug monitoring (TDM) of busulfan measuring plasmatic concentrations to estimate busulfan pharmacokinetic parameters can be used. TDM is now widely carried out in routine practices and aims to ensure the targeting of the reported therapeutic windows by individualizing busulfan dosing based on the clearance estimations from a previous dose.

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在特定人群中个体化布硫丹剂量和评估药代动力学药物相互作用的风险。

Busulfan是一种烷基化剂，广泛应用于造血干细胞移植调节，代谢复杂，个体间和个体内差异大，尤其是儿童。结合busulfan PK/PD关系的强大理论基础，改变其清除率的因素(如体重，年龄，主要是GST-A遗传多态性)也可以影响临床结果。涵盖领域:本综述旨在概述目前关于丁硫丹药代动力学的知识，其在儿科人群中的药代动力学变异性，药物-药物相互作用(DDI)，以及它们对剂量个体化的影响。本综述基于截至2021年10月的医学文献。专家意见:为了确保儿科学中有效的丁硫丹暴露，已经建立了不同的基于体重的诺图来确定丁硫丹的剂量，并提供了更好的结果(65-80%的患者正确暴露)。除了形态图，治疗药物监测(TDM)，测量血浆浓度，以估计药代动力学参数，可用于丁磺芬。TDM现在在常规实践中广泛开展，其目的是根据以前剂量的清除率估计，通过个体化布硫丹剂量来确保靶向报道的治疗窗口。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Opinion on Drug Metabolism & Toxicology 医学-生化与分子生物学

CiteScore

7.90

自引率

2.30%

发文量

审稿时长

4-8 weeks

期刊介绍： Expert Opinion on Drug Metabolism & Toxicology (ISSN 1742-5255 [print], 1744-7607 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on all aspects of ADME-Tox. Each article is structured to incorporate the author’s own expert opinion on the scope for future development. The Editors welcome: Reviews covering metabolic, pharmacokinetic and toxicological issues relating to specific drugs, drug-drug interactions, drug classes or their use in specific populations; issues relating to enzymes involved in the metabolism, disposition and excretion of drugs; techniques involved in the study of drug metabolism and toxicology; novel technologies for obtaining ADME-Tox data. Drug Evaluations reviewing the clinical, toxicological and pharmacokinetic data on a particular drug. The audience consists of scientists and managers in the pharmaceutical industry, pharmacologists, clinical toxicologists and related professionals.